Chronaki, Georgia, Garner Matthew, Hadwin, Julie, Sonuga-Barke, Edmund J.S. and Broyd, Samantha J. (2010). Electrophysiological correlates of emotion processing in children with ADHD.

ABSTRACTS

Eunethydis 1st international ADHD conference:from data to best clinical practice

26th–28th May 2010, Amsterdam, The Netherlands

Main Conference Lectures

Genetic effects in ADHD: current state of the art

Philip Asherson1, Barbara Franke2

1MRC Social Genetic and Developmental Psychiatry, Institute of

Psychiatry, King’s College London, London, UK; 2Donders Institute

for Brain, Cognition and Behavior, Departments of Human Genetics

and Psychiatry, Radboud University Nijmegen Medical Centre,

Nijmegen, The Netherlands

Abstract: ADHD has a complex aetiology, with both genetic and

environmental factors contributing to risk for the disorder. Family,

twin and adoption studies find high heritability in children that is

robust to different definitions and measurement of the disorder

indicating the importance of genetic influences. Genetic studies

have also turned their attention to the persistence of ADHD into

adulthood and findings from recent twin studies of ADHD in adult

populations will be described. Quantitative genetic approaches have

identified two main cognitive factors that explain most of the

familial effects on ADHD. Searches at the molecular level for the

actual genes and genetic variants involved have long relied on

candidate gene approaches. These have been able to uncover only a

small percentage of the genetic contribution to the disorder. More

recently, genome-wide association studies have been introduced,

discovering the involvement of unexpected genes and pathways in

the aetiology of the disorder. A new route in molecular genetic

studies in ADHD is the study of the involvement of multiple rare

variants of moderate to large effect size, in this case copy number

variants (CNVs). As in other psychiatric disorders, this type of

variant also seems to explain occurrence of the disorder in a per-

centage of ADHD patients and suggests considerable overlap with

other neurodevelopmental disorders. Because of the strong hetero-

geneity of ADHD, both clinically and genetically, new approaches

have been chosen to select phenotypes for genetic studies. Among

these, studies considering inclusion of comorbidity, studies in adults

with ADHD, as well as approaches employing intermediate phe-

notypes will be discussed.

Keywords: Genetic epidemiology, Single nucleotide polymorphism,

Copy number variant, Adult ADHD, Quantitative genetics, Twin

studies, Intermediate phenotypes

Neurophysiology

Tobias Banaschewski

Department of Child and Adolescent Psychiatry and Psychotherapy,

Central Institute of Mental Health, Mannheim, Germany

Introduction/methods: The millisecond time resolution of electro-

physiology provides a noninvasive method to monitor neural activation

patterns associated with a wide variety of brain states and processes in real

time. Spatial resolution has increased considerably through source imag-

ing and combined EEG-fMRI. In addition, real time feedback of neural

activity has found increasing therapeutic applications in neurofeedback

and brain computer interfaces. Specific brain functions underlying atten-

tion, inhibition, or response control can be separated with adequate ERP

tasks, for example the cued continuous performance test (cued CPT), and

EEG/ERP studies can reveal both psychophysiological precursors and

correlates of behavioural impairment. Recent electrophysiological

research on response inhibition, working memory, motivation, reward and

emotion processing in ADHD and the influence of medication is reviewed.

Results: Event-related potentials indicating attentional orienting,

preparation and response control (e.g., cue-P3, CNV, nogo-P3 during

cued CPT) revealed multiple attention and regulation problems rather

than isolated inhibition deficits in ADHD and help disentangling the

pathophysiological background of the comorbidity with oppositional

defiant disorder/conduct disorder. Abnormal brain activity related to

performance monitoring and error detection has been found in chil-

dren, adolescents and adults with ADHD (e.g., in the flanker task).

Familial effects on deviant EEG/ERP parameters indicate that these

parameters could be considered as putative endophenotypes. Recent

studies of resting-state functional connectivity indicate that altered

spontaneous very low frequency brain activity may interfere with

higher cognitive functions.

Discussion/conclusion: Over the past decade, EEG/ERP research has

contributed substantially to our understanding of altered brain pro-

cesses and functions underlying ADHD. Although deficient response

inhibition has been proposed as the core deficit in ADHD, electro-

physiological studies show that ADHD cannot be fully explained by

an inhibition-specific deficit. EEG/ERP and multimodal imaging

studies are promising tools for multilevel investigations of etiological

pathways into ADHD, and neurophysiological markers become

increasingly important as targets for treatment.

Keywords: Event-related potentials, EEG, Error-related negativity,

P300, Endophenotypes

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Eur Child Adolesc Psychiatry (2010) 19 (Suppl 1):S5–S91

DOI 10.1007/s00787-010-0117-5

Neuroscience of ADHD: basic and applied issues

Russell A. Barkley

Medical University of South Carolina, Charleston, USA

Introduction and objective(s): This presentation will discuss two

related issues that are essential to further research into the neurosci-

ence of ADHD: (1) What endophenotype is most suitable to study

ADHD and (2) What is the nature of executive functioning (EF) in

ADHD?

Discussion: Research findings related to these two issues as well

as an analysis of the concepts endophenotype and EF will be

discussed emphasizing the limitations that are placed on research

by viewing both as unitary and uni-level. Investigators will also

benefit from an awareness of natural selection in biological

evolution for generating hypotheses as to the adaptive problems

that are solved by the evolution of specific endophenotypes

or EFs.

Conclusion: Both the concept of endophenotype and of EF need

to be considered as multi-component, multi-level constructs in

the context of human evolution and selecting mechanisms

(physical environment, social environment, sexual selection)

rather than being unitary, uni-level, and devoid of an evolu-

tionary context. Selection of the component and level of each to

be studied will be based upon the hypotheses of the investigator

and whether getting closer to neurological processes or con-

versely to the levels of behavioural and social functioning at

which natural selection operates best serve the investigator’s

goals.

Keywords: Attention deficit hyperactivity disorder (ADHD), Endo-

phenotype, Executive functioning, Ecological validity

Neurofeedback training

Daniel Brandeis

Department of Child and Adolescent Psychiatry, University of Zurich,

Zurich, Switzerland; Center for Integrative Human Physiology

(ZIHP), University of Zurich, Zurich, Switzerland; Department of

Child and Adolescent Psychiatry and Psychotherapy, Central Institute

of Mental Health, Mannheim, Germany

Correspondence address: Prof. Dr. Daniel Brandeis, Developmental

Clinical Neurophysiology, Department of Child and Adolescent

Psychiatry and Psychotherapy, Central Institute of Mental Health, J5,

68159 Mannheim, Germany

Introduction and objective(s): A number of recent controlled studies

have established sizeable and sustained therapeutic effects of neuro-

feedback training in children with ADHD. However, the specific

mechanisms involved, and the contribution of learned control over

specific brain functions and states are less clear.

Methods: The review will cover the neurophysiological rationale and

recent evidence for neurofeedback treatment in ADHD. Selected

papers, reviews and metaanalyses are examined for strengths and

limitations of the approach. Also related research on relevant mech-

anisms such as neurofeedback effects on sleep EEG, and BCI (brain

computer interface) studies will be addressed.

Discussion: The discussion will focus on the importance of specific

treatment effects, on the advances and clarifications expected from

ongoing trials, and on important areas for future research.

Keywords: ADHD, EEG, Plasticity, Neurofeedback, Self-regulation

Gene–environment interactions in ADHD

Jan K. Buitelaar

Department of Cognitive Neuroscience, Radboud University

Nijmegen Medical Center, Nijmegen, The Netherlands

Twin and adoption studies have indicated that ADHD has a strong

genetic loading with estimated heritabilities around 0.80. Though the

involvement of a number of candidate genes as DRD4, DRD5, DAT1,

DBH, 5-HTT, HTR1B, SNAP25 had been replicated in meta-analyses

based on the results of conventional family-based and case–control

designs, none of these was replicated at the level of genome-wide

significance (p \ 0.05 9 10-8) in recent GWAS studies. These

GWAS studies did not reveal either other signals at the level of gen-

ome-wide significance. This supports the ‘‘common variant common

disease model’’ of ADHD that describes polygenic influences (i.e.

multiple interacting genes, each of small effect size with odds ratios

1.01–1.5) together with gene/environmental interactions (G9E) being

responsible for individual phenotypes. Recent reports indicate that also

rare variants with strong effects may contribute to ADHD, but it is

unclear for which proportion of ADHD cases this is relevant, pending

further studies. The overall effect size of G9E is difficult to estimate

since this is included in the compartment of additive genetic effects in

twin models of heritability. The lack of genes with major pathogenic

effects suggests however that gene-specific vulnerabilities may be

balanced by adaptive advantages in certain circumstances, and implies

aetiological heterogeneity. The aim of this presentation is to review the

various theoretical models of G9E, include epigenetic effects of the

environment of the expression and regulation of genes, variations in

heritability according to the environment, and G9E sensu strictu.

Next, to discuss findings from a series of recent studies on G9E in

ADHD. Current findings include interaction effects of DAT with the

early prenatal environment (exposure to alcohol and smoking) and

psychosocial environment, DRD4 and the sensitivity to parenting

behaviour, and 5-HTT to environmental adversity and socio-economic

status. We will also pay attention to G9E in explaining the comor-

bidity with conduct disorder in ADHD, such as the interaction between

parental expressed emotion, and variation of DAT and 5-HTT. Further

elaboration of G9E models of ADHD may lead to resolving the

aetiological heterogeneity of ADHD, and on the basis thereof, may

lead to implications for treatment.

The (backward) neuro-pharmacology of ADHD

David Coghill

Child and Adolescent Psychiatry, Centre for Neuroscience, University

of Dundee, Scotland, UK

Introduction: Whilst medications are recognised as important front

line treatments for ADHD it is also important to recognise that drugs

can also play an important role as probes to develop our under-

standing of the underlying pathophysiology of this disorder.

Results: This presentation will selectively but critically review some

important recent psychopharmacological studies from the basic sci-

ence, neuroimaging and neuropsychopharmacological literature that

have utilised both stimulant and non-stimulant medications as tools to

uncover the dopaminergic and noradrenergic mechanisms, the

neuroanatomical pathways and the cognitive processes that make

causal contributions to the development of ADHD.

Discussion: Whilst psychopharmacology has already provided

important information about the pathophysiology of ADHD this is

S6 Eur Child Adolesc Psychiatry (2010) 19 (Suppl 1):S5–S91

123

currently a somewhat neglected area of research and there remain

many unanswered questions.

Keywords: Pharmacology, Stimulant medication, Atomoxetine,

Neuroimaging, Neuropsychology, Animal models

Limitations of psychological treatment

Manfred Dopfner

Several psychological approaches aiming at the reduction of ADHD

and comorbid symptoms have been developed and evaluated in the

last 40 years. Treatment approaches focusing on the modification of

parent–child interactions utilizing behavioral parent management

trainings have been shown to be efficacious in the reduction of ADHD

core symptoms as well as comorbid problems at least in younger

children. Several studies document that behaviorally based interven-

tions in the classroom effectively reduce disturbing classroom

behavior. However, trials show that the treatment effects are lower

compared to the effects of pharmacological interventions and the

additional benefit of combined psychological and pharmacological

treatment is not well established. The findings regarding the effects on

ADHD core symptoms are inconsistent. Moreover, the interventions

are less effective in parents with impulsivity and inattention. The

main problem of behavioral treatment is the implementation of spe-

cific interventions in the natural setting in the family or at school.

Approaches aiming at the improvement of the implementation pro-

cedures and further enhancement strategies will be discussed. In the

recent years interventions for adolescents have been developed.

However, research on the effects of treatment in this population is

lacking. Overall, the stability of treatment effects is not well estab-

lished, since only a few studies document long-term stability of the

effects of behavioral interventions. Interventions to improve stability

of treatment effects are discussed.

Imaging genetics of ADHD

Sarah Durston

Rudolf Magnus Institute of Neuroscience, University Medical Center

Utrecht, Utrecht, The Netherlands

Introduction and objective(s): This presentation will discuss neu-

roimaging as an endophenotype for investigating the role of dopamine

genes in ADHD. Several viable candidate genes have been implicated

in ADHD, including the dopamine DRD4 and DAT1 genes. Neuro-

imaging studies have resulted in a good understanding of the

neurobiological basis of deficits in cognitive control in this disorder.

Methods: At a genetic level, we are investigating the effect of ADHD

candidate genes. The dopamine-transporter (DAT1) gene is a strong

candidate, as it has been implicated repeatedly in ADHD.

Results: We showed that DAT1 genotype affects activation in stria-

tum and cerebellar vermis, partially mirroring the effects of stimulant

medication that also works on the dopamine transporter.

Discussion: These findings suggest that brain activation associated

with cognitive control is sensitive to familial and genetic influences.

Conclusion: The results from this kind of work show that neuroim-

aging is useful as an endophenotype in investigating dopamine gene

effects in ADHD. Other avenues of investigation are suggested by a

combination of data- and theory-driven approaches in both genetics

and neuroimaging.

Keywords: Neuroimaging, Genetics, Dopamine transporter, Endo-

phenotype, Cognitive control

The aetiology of ADHD: current challenges and future

prospects

Stephen V. Faraone

Departments of Psychiatry and Neuroscience and Physiology, SUNY

Upstate Medical University, Syracuse, USA

Introduction and objective(s): The goal of this talk is to provide a

broad overview of what is known about the aetiology of ADHD and

suggest new directions for ADHD research.

Methods: Review of the literature.

Results: Numerous studies support the conclusion that ADHD is a

disorder of the brain and that the susceptibility to ADHD is influenced by

both genes and environmental risk factors. No single risk factor is nec-

essary and sufficient to cause ADHD in the large majority of cases.

Discussion: Progress in understanding the aetiology of ADHD will

require very large samples and collaborative multidisciplinary pro-

jects. Such work should: (a) take the potential for false positive

findings seriously, (b) search for novel methods of diagnosis that rely

on biological, rather than clinical features and (c) focus on mecha-

nistic rather than descriptive goal.

Conclusion: Our understanding of ADHD’s aetiology has increased

dramatically over the past two decades. Yet, because aetiological

research has not yet let to improvements in diagnosis or treatment, a

new paradigm for such research is needed.

Keywords: ADHD, Aetiology, Genetics, Environment, Brain

Working memory training

Torkel Klingberg

Karolinska Institute, Stockholm, Sweden

In a series of experiments we have investigated the behavioral and

neural effects of working memory training (Klingberg et al. 2002,

2005; Olesen et al. 2004; McNab et al. 2009; Holmes et al. 2009a, b).

These studies show that training improve performance of transfer

tasks requiring working memory and top-down control of attention

and also decrease symptoms of inattentiveness in ADHD. The

behavioral effects seem to last at least 6 months. At the neural level,

training has been associated with increased brain activity in frontal

and parietal regions as well as changes in the cortical dopamine D1-

receptors. The implications of these findings for developmental neu-

roimaging will be discussed.

The developmental consequences of ADHD

Benjamin B. Lahey

University of Chicago, Chicago, USA

Introduction and objective(s): Longitudinal data are presented that

demonstrate that the diagnosis of ADHD in young children has pre-

dictive validity through adolescence. The objective is to be able to

describe the long-term maladaptive sequelae of ADHD in early

childhood that indicate the ADHD is a valid disorder.

Methods: Longitudinal study involving 11 structured assessments

over 14 years of children who met DSM-IV criteria for ADHD at

4–6 years and demographically matched comparison children.

Results: Like children with ADHD at older ages, all three subtypes of

ADHD at 4–6 years of age reliably predict serious social and

Eur Child Adolesc Psychiatry (2010) 19 (Suppl 1):S5–S91 S7

123

academic impairment and risky behavior over many years. In addi-

tion, early ADHD is a robust predictor of depression and suicide

attempts in adolescence. The best predictors of specific patterns of

future outcomes are the initial numbers of inattention and hyper-

activity-impulsivity.

Discussion: This is the first long-term longitudinal study to use DSM-

IV diagnostic criteria for ADHD and it provides the longest follow-up

period of ADHD in young children.

Conclusion: All subtypes of ADHD at 4–6 years of age are serious

conditions with highly significant long-term consequences.

Keywords: Attention-deficit/hyperactivity disorder (ADHD), Sub-

types, Predictive validity, Depression, Suicide attempts

Neural circuits as mediators of aetiological risk;

a target for translational psychiatry

A. Meyer-Lindenberg

University of Heidelberg, Heidelberg, Germany; Central Institute of

Mental Health, Square J 5, 68159 Mannheim, Germany

Environmental risk factors such as urbanicity, migration, drug use and

social status contribute to the risk of many psychiatric disorders.

However, the neural mechanisms mediating these risks are just now

beginning to come into focus. It is likely that many epidemiologically

identified risk factors are proxies for underlying stressors that need to

be clarified and, if this process is successful, can me mined as

potential targets for translation. We illustrate this approach with

recent work on social stress and social status. We show an impact of

prefrontal circuits regulating limbic structures associated with the

processing of emotion. Finally, we relate these circuit to a transla-

tional approach utilizing the prosocial neuropeptides, oxytocin and

vasopressin, which impact on amygdala and regulatory circuits.

Common and unique effects of methylphenidate

and atomoxetine in the treatment of ADHD

Jeffrey H. Newcorn

Mount Sinai School of Medicine, New York, USA

Objective: This presentation will provide information regarding the

mechanisms of action and response profiles for methylphenidate

(MPH) and atomoxetine (ATX), and illustrate the importance of

identifying common and unique neurobiological effects of these dif-

ferent treatments.

Background: There has been considerable interest in the develop-

ment of new stimulant and non-stimulant medication treatments for

ADHD. These stimulant and non-stimulant treatments share common

neurobiological properties, but also differ in several important ways.

Method: 35 youth treated in randomized trials of ATX or MPH had

fMRI scans before and after 6 weeks of treatment, while performing a

go/no-go task. Common activations (extent threshold = 100 voxels;

p \ 0.05) were identified via conjunction analyses and unique acti-

vations were identified via t tests.

Results: Consistent with findings from animal models, we hypothe-

size common activations in several areas within the prefrontal cortex

and dorsal anterior cingulate cortex, as well as unique activations for

MPH in caudate and unique activations for ATX in posterior cingu-

late cortex and temporoparietal cortex.

Conclusions: Common activation effects of MPH and ATX are

consistent with the finding that many individuals respond to both

treatments; unique activations provide a basis for understanding dif-

ferential response. Better understanding these effects holds promise

for developing individualized approaches to clinical care.

Are there neuropsychological subtypes in ADHD?

Joel T. Nigg

Psychology Division, Department of Psychiatry, Oregon Health and

Science University, Portland, USA

ADHD is likely to be a heterogeneous condition not only in regard to

clinical manifestation but with regard to neurological mechanisms. In

this lecture, heterogeneity will be described in regard to cognitive

decrements observed in some children. Then, approaches to resolving

heterogeneity using endophenotype measures will be described, ref-

erencing neuropsychological measures, temperament measures, and

brain imaging (functional connectivity) measures. Different method-

ological approaches will be illustrated. In conclusion, observations

will be presented regarding the pros and cons of studying ADHD with

regard to neuropsychological subtyping.

Is ADHD an established risk factor for ADHD?

Jaap Oosterlaan

Department of Clinical Neuropsychology, VU University

Amsterdam, Amsterdam, The Netherlands

Introduction and objective(s): Low birth weight and preterm birth

have both been associated with attentional problems and ADHD. This

study reviews epidemiological studies investigating the association

between very low birth weight (VLBW,\1,500 g)/extremely preterm

birth (\32 weeks of gestational age) and both ADHD symptoms and

the diagnosis of ADHD.

Methods: Systematic review.

Results: Symptoms suggestive of ADHD are more frequently

observed in children with VLBW and children born extremely pre-

term with effect sizes in the moderate range. Odds ratios for the

diagnosis of ADHD vary greatly and average around 3.

Discussion: ADHD and symptoms associated with ADHD are fre-

quently observed in children with VLBW/children born extremely

preterm. Comorbidity with other disruptive behaviour disorders seems to

be virtually absent in this group. VLBW/extremely preterm birth children

with ADHD seem to be an etiologically distinct subgroup of ADHD.

Conclusion: VLBW/extremely preterm birth is an established risk

factor for ADHD.

Keywords: Systematic review, ADHD, Very low birth weight,

Extremely preterm, Pathophysiology

Key clinical developments in the diagnosis of ADHD

Luis Rohde

Department of Psychiatry, Federal University of Rio Grande do Sul,

Porto Alegre, Brazil

The development of classification systems in psychiatry has been a

very complex task. In clinical settings, these classification systems

help communication about disorders among professionals and


123

between them and their patients. There is a recent interest on

opportunities for improving the nosology of ADHD in future classi-

fication systems like the DSM-V and the ICD-11. This presentation

addresses the following issues: (a) Do differences between DSM-IV

and ICD-10 criteria for ADHD/HKD have any clinical and research

impact? (b) Should ADHD criteria be modified to capture a more

dimensional perspective that provides a better understanding for the

disorder? (c) Do new classification systems for ADHD need to be

more developmentally sensitive? (d) Should different criteria and/or

thresholds according to gender be incorporated? (e) Do we need more

data on validity for different aspects of the ADHD criteria as pro-

posed in the DSM-IV? (f) Is age-of-onset of symptoms/impairment a

valid criterion for ADHD? (g) What need to be fixed in the criteria to

make them clinically acceptable for adults?

The potential of endophenotypes in ADHD

Nanda N.J. Rommelse

Radboud University Medical Center, Nijmegen, The Netherlands;

Karakter Academical Centre for Child and Adolescent Psychiatry,

Nijmegen, The Netherlands; Donders Centre for Neuroscience,


Correspondence address: Nanda N.J. Lambregts-Rommelse, Rad-

boud UMC, Reinier Postlaan 12, 6525 GC Nijmegen, The

Netherlands

Introduction and objective(s): The endophenotype concept has been

introduced over 35 years ago in psychiatric research. Endophenotypes

are proposed to intermediate between genotype and phenotype. The

main reasons for including endophenotypes into genetic studies of

ADHD, is to unravel the modes of action of known risk genes and to

discover new risk genes for the disorder. Main objectives of this talk

are to present a comprehensive overview of the ADHD endopheno-

typic literature and to formulate recommendations for future studies.

Methods: All relevant studies in the ADHD endophenotypic literature

will be included.

Results: Promising findings into the modes of action of ADHD

risk genes on cognition and brain activation patterns have been

reported. However, no consistent pattern of findings has yet emerged.

Discussion and conclusion: Substantially larger sample sizes, ‘golden

standard’ cognitive test batteries (a freely accessible computer-driven

battery with a broad range of tasks examined for their validity, reli-

ability and heritability), longitudinal samples and the assessment of

comorbid disorders will improve significance and comparability of

results.

Keywords: Endophenotypes, Genetics, Neuropsychology,

Comorbidity

Neuroimaging in ADHD: from bench to bedside?

Katya Rubia

Department of Child and Adolescent Psychiatry, Institute of

Psychiatry, King’s College London, London, UK

Modern structural and functional neuroimaging studies over the last

decade have substantially advanced our knowledge of the brain

deficits in children and adults with ADHD. Structural findings

demonstrate that ADHD is a maturational delay of normal brain

development, affecting frontal, striatal, cerebellar and temporo-

parietal brain regions and networks. Functional imaging studies have

shown concomitantly reduced activation and inter-regional functional

connectivity of the same brain regions. Some of these regional

abnormalities (i.e., the inferior prefrontal dysfunction) appear to be

disorder-specific for ADHD when compared to other child psychiatry

disorders, are associated with dopamine genotypes in gene-imaging

studies (i.e. inferior prefrontal cortex and caudate) and can be up-

regulated with methylphenidate as shown by pharmacological

imaging studies. While modern imaging has substantially advanced

our knowledge of the brain abnormalities of ADHD, the clinical

impact has been minimal. The next decade needs to find ways to

apply this knowledge to the bedside which will be the focus of my

talk.

Keywords: ADHD, MRI, fMRI, Inferior prefrontal lobe, Specificity,

Methylphenidate

Reinforcement and reward processes

Terje Sagvolden

University of Oslo, Oslo, Norway

Introduction and objective(s): I will review evidence for altered

reinforcement processes in ADHD [1]. We have been using behavioural,

genetic, neuroanatomical, neurochemical and neurophysiological

methods [2]. Results from several areas of research indicate altered

reinforcement and learning processes [3, 4].

Keywords: Animal models, Genetics, Neurobiology, ADHD

References

1. Sagvolden T, Johansen EB, Aase H, Russell VA (2005) A

dynamic developmental theory of attention-deficit/hyperactivity

disorder (ADHD) predominantly hyperactive/impulsive and

combined subtypes. Behav Brain Sci 28:397–468

2. Sagvolden T, Johansen EB, Woien G, Walaas SI, Storm-

Mathisen J, Bergersen LH et al (2009) The spontaneously

hypertensive rat model of ADHD—the importance of selecting

the appropriate reference strain. Neuropharmacology 57:619–626

3. Johansen EB, Killeen PR, Sagvolden T (2007) Behavioral

variability, elimination of responses, and delay-of-reinforcement

gradients in SHR and WKY rats. Behav Brain Funct 3:60

4. Johansen EB, Killeen PR, Russell VA, Tripp G, Wickens JR,

Tannock R et al (2009) Origins of altered reinforcement effects in

ADHD. Behav Brain Funct 5:7

Getting to grips with Fidgety Phil

Joseph A. Sergeant

Department of Clinical Neuropsychology, Vrije Universiteit,

Amsterdam, The Netherlands

Introduction and objective: This paper reviews the primary neuro-

biological research on what is currently termed attention deficit

hyperactivity disorder (ADHD) in the last 35 years that have con-

tributed to our understanding of the aetiology and treatment of the

disorder.

Method: Selected review of major papers, meta-analyses and reviews

in ADHD.

Results: There will be indicated key problems and issues that chal-

lenge the field.

Discussion: Integration of the field theoretically has begun but

requires development both domain specific and cross-domain models.


123

The primary design of research needed to further the field requires a

clinical developmental neuroscience approach especially in proband-

sib comparisons.

Conclusion: Significant advances in both our understanding of

ADHD and its treatment in both child and adult ADHD have taken

place in the last 35 years.

Environmental influences in ADHD: experimental

and observational studies

Edmund Sonuga-Barke

Institute for Disorder of Impulse and Attention, School of

Psychology, University of Southampton, Southampton, UK;

Department of Experimental Clinical and Health Psychology, Ghent

University, Ghent, Belgium

Over the past decade studies of ADHD aetiology have focused pre-

dominantly on genetic determinants. Out of all this research has come

an emerging realization of the limited value of causal models that

focus exclusively on genetic factors. At the same time there is a

growing understanding of the potential power that the social and

physical environment has to shape human brain development more

generally. Together these developments have led to a refocusing of

serious scientific attention on the role of the environment as a causal

factor in ADHD. In this talk I review some existing data from

experimental, quasi-experimental and observational studies that pro-

vide support for this hypothesis. The findings will be discussed in the

context of recent models of biological programming and brain plas-

ticity. Directions for future research on the mechanisms of

environmental influence in ADHD will be described.

Headstrong and irritability: same or different

pathways?

Argyris Stringaris

Institute of Psychiatry, PO85, Denmark Hill, London SE5 8AF, UK

High levels of irritability are common in children with ADHD.

However, the reasons for this association remain unclear. In this talk,

I will present work on probing the following alternatives: (a) irrita-

bility may be a merely non-specific consequence of ADHD; (b)

irritability may be an integral part of ADHD, for example the man-

ifestation of a broader problem of behavioural regulation; (c)

irritability may be a dimension spanning across psychopathology. I

will show results from clinical cohorts and from three longitudinal

community studies: the UK-based Environmental-Risk (E-Risk)

Longitudinal Twin Study (E-Risk) and the Office for National Sta-

tistics study on children’s mental health, along with the US-based

Children in the Community study. I will draw on our work describing

dimensions of oppositional defiant disorder and our modelling of

comorbidity in developmental psychopathology with some reference

to the pediatric bipolar debate. Based on path analytic and hierar-

chical modelling approaches I will show evidence suggesting that

irritability may be best seen as a dimension of liability for mainly

depressive and anxiety disorders. I will also focus on the strong

relationship of irritability with a headstrong behaviour dimension, that

is itself related to ADHD and conduct problems. I will focus on the

challenges presented by inter-correlated dimensions in psychopa-

thology and on the importance of refining measurement. I will

conclude with an attempt to answer the questions: what are the best

strategies to identify dimensions of risk in psychopathology and how

can we use them to inform clinical decision making and treatment.

Key research developments on the clinical diagnosis

of ADHD

Rosemary Tannock

University of Toronto, The Hospital for Sick Children, Toronto,

Canada

Introduction and objective(s): To discuss the factor structure of the

DSM-IV symptoms of ADHD and the need to obtain information

from multiple informants.

Methods: The factor structures of DSM-IV symptoms of ADHD were

assessed in independent clinical samples: 189 adolescents and their

parents and 751 adults with ADHD, who were assessed with clinician

interviews. Four possible factor structures for the 18 ADHD symp-

toms were tested using confirmatory factor analysis: two models with

correlated factors and two bifactor models.

Results: Bifactor models with one general and two (inattention and

hyperactivity/impulsivity) two specific factors best accounted for

adolescent symptoms, according to both parent and adolescents’

reports. Replication of these findings from behavioral rating scales

completed for this sample by parents and teachers indicates that the

findings are not method- or informant-specific or three (inattention

and separate motoric and verbal symptoms of hyperactivity/impul-

sivity) specific factors best accounted for the symptoms in both

samples. Bifactor models with one general and two (inattention and

hyperactivity/impulsivity) or three (inattention and separate motoric

and verbal symptoms of hyperactivity/impulsivity) specific factors

best accounted for the adults’ symptoms.

Conclusion: These results suggest that there is a unitary component

to ADHD symptoms as well as separable dimensional specific factors.

Keywords: ADHD, Factor structure, Bifactor models

Translational science in ADHD

Eric Taylor

King’s College London Institute of Psychiatry, London, UK

In the decades since Professor Sergeant turned his attention to

ADHD, much has changed. Prevalence has remained similar, but

recognition has increased dramatically. The sophistication of sci-

entific theory and techniques has increased beyond all expectation.

Basic science and clinical application have had a complex interac-

tion, and this talk reviews the extent to which several sciences have

been able to influence or to learn from the clinic. The application of

psychological theory, and its embodiment in psychological tests

(including functional neuroimaging) has had a profound, if some-

what intangible effect in driving public and professional

understanding of the disorder. It was highly relevant in the devel-

opment of DSM-III; it has been the key evidence cited to sustain

campaigns such as ‘‘ADHD is Real’’; it is used in recommendations

made about the education of individual children. Studies on delay of

reward have influenced how practitioners have developed behaviour

modification techniques to suit children with ADHD (though it is

still unclear how far this application has improved outcomes). Nat-

urally enough, translational psychological approaches have had

adverse effects as well: the incorrect use of tests such as the CPT to

diagnose ADHD is still widespread; the application of neurometrics


123

led to the denial of remedial education for some children in some

countries. It has also had limitations: there is still rather little in the

way of standardised and normed instruments for key functions. For

the future, psychological analysis seems likely to lead to a differ-

entiated approach to recognition and remediation of distinct

components of disorder. The application of pharmacology—partic-

ularly pharmacokinetics—has had a clear and direct influence on the

formulations of medicines used for the treatment of ADHD. We can

envisage the arrival of cognitive enhancers, and should prepare our

clinical thinking for how to react. It can be argued however that the

interaction has been more in the opposite direction: the striking

effect of central nervous system stimulants has given the clues to

molecular sciences about where to look for neurotransmitter and

genetic contributions to the origins of disorder. The application of

genetic science is still in its infancy and it is too early to do anything

but speculate about its likely impact in the future. Genetic coun-

selling, pharmacogenomics and new drug development all seem very

likely outcomes. At the moment, applications to diagnosis, to deci-

sions about care, to re-ordering the psychiatric classifications or to

early screening all seem less probable, at any rate in the near future.

Rather similarly, the explosion of knowledge about brain structure

and function seems at present to have clear implications for how we

might analyse the reasons for individuals being refractory to treat-

ment; and for new drug discovery. Neurological impact on diagnosis

and individual formulation, by contrast, seem remote. The impact of

genetics and understanding of the brain on public perception are at

present unpredictable: will they lead to fatalism? To stigma? To a

more problem-solving approach? The application of epidemiology

has already been strong. Longitudinal studies have opened up adult

ADHD for better understanding and treatment. They have con-

tradicted a formerly prevalent view that ADHD is an immaturity

which people outgrow (together with neuroimaging evidence that the

brain problems themselves persist into adult life, not only the

behavioural sequelae). The findings of the impact of parenting upon

function—and the demonstration that genetic influences do not

account for the association—has already led to better appreciation of

the scope for psychological interventions. Indeed, the knowledge of

what factors determine the course of affected people is more relevant

to what clinicians do than knowledge about the causes that initiate.

Some potential applications have not yet happened. Embryology will

need to be applied if we are to get anywhere on early intervention.

The development of large longitudinal cohorts may well give better

information about the early environmental influences that will need

to be mastered. It will be important to recognise that translation is

not only the immediate application of technology, but a key idea in

long-term research strategies.

Therapeutic use of stimulants in ADHD

Timothy Wilens

Clinical and Research Programs, Pediatric Psychopharmacology,

Massachusetts General Hospital, Harvard Medical School,

Boston, USA

Introduction and objective(s): Attention deficit/hyperactivity disor-

der (ADHD) is the most common neurobehavioral disorder presenting

for treatment in youth. Pharmacotherapy with the stimulant medica-

tions plays an important role in the treatment of ADHD across the

lifespan.

Methods: A selective review of the recent literature was completed

focusing on basic and clinical data related to stimulant treatment for

ADHD.

Results and discussion: New findings on the neurobiology and

pharmacology of the stimulants has emerged. Likewise, recent clin-

ical stimulant trials have been reported in specific ADHD groups

including preschoolers, adolescents, adults, and those with psychiatric

and substance use comorbidities. New data on longer term effects of

stimulants on the biology and course of ADHD will be reported.

Current safety controversies related to longer term use of the stimu-

lants will be presented.

Conclusion: Much recent information is now available guiding the

clinical understanding of stimulants in the treatment of ADHD.

Keywords: ADHD, Stimulants, Amphetamine, Methylphenidate,

Neurobiology

The danger of drugs

Alessandro Zuddas

Section of Child Neuropsychiatry, Department of Neuroscience,

University of Cagliari, Cagliari, Italy

Introduction: A large number of meta-analyses indicate that meth-

ylphenidate, amphetamines, and atomoxetine are effective drug and,

combined with psychosocial intervention, should be considered as

potential first treatments for children and adolescents with ADHD.

Nevertheless, the safety of ADHD medications is not fully known:

concerns have arisen about the lack of contemporary-standard infor-

mation for medications originally licensed several decades ago, as

well for signals of possible harm arising from more recently devel-

oped medications.

Methods: The guidelines group of the European Network for

Hyperkinetic Disorders (EUNETHYDIS) reviewed the available lit-

erature on the ADHD medication licensed in Europe about

cardiovascular, neurological (sleep, epilepsy and tics), growth and

psychiatric (irritability, suicidal ideation, psychosis) side effects, and

on the risk of abuse, misuse and drug diversion. Frequency, possible

causal mechanisms, mediating factors and managing strategies were

analyzed for specific adverse events.

Results: Some of the effects examined appeared to be minimal in

impact or difficult to distinguish from risk to untreated populations.

Several areas require further study to allow a more precise under-

standing of the medication risks. This allowed the group to develop

specific recommendation for screening before prescription and pre-

caution during treatment. Before prescription heart rate and blood

pressure (plotted on a percentile chart), history of exercise syncope,

undue breathlessness and other cardiovascular symptoms as well as

the family history of cardiac disease should be assessed: in the

presence of specific risks a frank discussion of these aspects between

the family, ADHD specialist and paediatric cardiologist should help

to refine the acceptability for the individual patient. During treatment

height, weight, blood pressure and heart rate should be monitored

regularly and compared to age-matched norms. All patients should be

carefully screened before treatment, and regularly monitored during

treatment, for psychiatric disorders such as depression, suicidal

thoughts, hostility, psychosis, mania and the risk for substance misuse

and drug diversion. Common symptoms such as headache, insomnia,

anorexia, nausea and any specific problems emerging in the individual

patient should also be monitored. Medications (atomoxetine in par-

ticular) should be discontinued in patients with jaundice or laboratory

evidence of liver injury and should not be restarted.

Discussion/conclusion: With a caveat for the several areas of

uncertainty, the impact of risk of ADHD treatment, and the balance of

that risk against possible benefits of treatment is favourable in most

cases: accurate screening before starting medications and monitoring

during treatment is always strongly recommended.


123

Early Career Lectures

Atypical default network connectivity in youth

with ADHD

Damien A. Fair1, Jonathan Posner3, Bonnie J. Nagel1,2,Deepti Bathula1, Taciana Cost Dias1, Kathryn Mills1,Michael S. Blythe1, Aishat Giwa1, Colleen Schmitt1, Joel T. Nigg1,2

1Department of Psychiatry, Oregon Health and Science University,

Portland, USA; 2Department of Behavioral Neuroscience, Oregon

Health and Science University, Portland, USA; 3Department of

Psychiatry, Columbia College of Physicians and Surgeons, New York

State Psychiatric Institute, New York, USA

Introduction: It has recently been suggested that the integrity of the

brain’s default network may provide a crucial avenue for under-

standing the neurobiology of ADHD. The default network refers to a

set of brain regions, originally defined by Shulman and colleagues [1],

that it consistently decreases in neural activity from baseline during

most goal-directed tasks. With its broad implications for brain func-

tioning, this network has recently become a key focus of

neuroscientific and psychiatric research. Evaluations of the default

network have increased significantly in recent years as the result of

using the relatively new technique of resting-state functional con-

nectivity MRI (rs-fcMRI). rs-fcMRI measures spontaneous intrinsic

correlated blood oxygen level dependent (BOLD) activity while

subjects are at rest, not performing an explicit task. Resting-state

fcMRI analyses have now established that spontaneous intrinsic

activity between regions of the default network is highly correlated or

functionally connected in adulthood [2]. Correspondingly, rs-fcMRI

studies in adults with ADHD [3] suggest reduced coherence in the

default network. This finding is intriguing in light of recurrent results

indicating that the coherence of the default network strengthens with

development [2]. Together, these considerations suggest that the rs-

fcMRI reports in adult ADHD may relate to or represent a disorder of

delayed or disrupted brain maturation. However, if an abnormality in

the consolidation of this network over development is central to the

pathophysiology of ADHD, it should be apparent prior to adulthood.

Therefore, it is crucial to determine whether an altered developmental

picture can be detected using rs-fcMRI in children with ADHD. To

that end, the present study utilized the typical developmental context

provided by Fair et al. [2] to examine coherence of brain activity

within the default network in children with and without ADHD.

Methods: Participants: A total of 23 ADHD participants and 23 age-

matched healthy control (aged 7–16 years) participants were included in

the current study. Data acquisition, processing, graph analyses: Partic-

ipants were scanned using a 3.0 Tesla Siemens Magnetom Tim Trio

scanner at the OHSU Advanced Imaging Research Center. For functional

images during rest periods, children were instructed to stay still, and

fixate on a standard fixation-cross in the center of the display. Functional

images were processed with traditional methods to reduce artifacts.

Additional connectivity preprocessing was also used and followed prior

methods as well [2]. Resting-state (fixation) data (420–630 s) from all 46

participants were included. Twelve a priori ROIs were selected and

analyzed based on their involvement in the default network shown in a

previous studies [2]. The resting-state BOLD time series were correlated

region by region for each participant across the full length of the resting

time series. Group comparisons were performed as previously described

[2]. To explore the extent to which connections related to component

symptom dimensions (i.e., hyperactivity-impulsivity versus inattention),

we performed a partial regression of connection strength as a function of

Conner’s T scores (parent).

Results: We found that correlated spontaneous activity within the

default network is reduced in children with ADHD. We further

showed that specific functional connections, previously shown as

developmentally dynamic [2], were also atypical in children with

ADHD. These findings are consistent with perturbation in the typical

developmental trajectory of circuit consolidation. Lastly, we found

that this reduced connectivity seems specifically related to symptoms

of hyperactivity-impulsivity rather than to symptoms of inattention.

Discussion: Fair et al. [2] reported that coherence in the default

network measured via rs-fcMRI strengthens over development. The

present findings which show reduced connectivity within this network

in ADHD compared to age matched controls is, in part, consistent

with, and renews assertions that ADHD is a disorder of delayed

maturation. With that said, we do not know whether the pattern seen

here will prove to be a true delay (with the potential for later ‘‘catch

up’’) or an aberrant developmental trajectory when examined longi-

tudinally. The fact that a large number of patients do not outgrow

their ADHD status and that disrupted default network connectivity

persists in patients with adult ADHD [3] suggests that multiple

mechanisms are at play, and that a ‘delay only’ portrayal will be

insufficient to fully characterize ADHD populations. Another ques-

tion that remains is whether the atypical developmental picture seen

here is specific to ADHD. Work in Tourrette Syndrome and autism

has shown a similarly delayed maturational trajectory via rs-fcMRI.

Thus, it remains unclear whether the pattern of altered connectivity

seen here will prove to be disorder-specific, or rather a generalized

principle that links many developmental neuropsychiatric disorders.

Conclusion: In this report we have shown the atypical nature of the

default network in ADHD children and young adolescents. We also

found evidence that reduced connectivity of the default network

tracks more strongly to hyperactive/impulsive symptoms than inat-

tentive symptoms. Finally, we found that the effects were consistent

with failure of normal circuit maturation in this network. Subsequent

connectivity investigations with large sample sizes and multiple

diagnostic groups should not only enable better characterizing of

subtypes within diagnostic groups (i.e., heterogeneity), but also aid in

identifying atypical developmental principles that track across mul-

tiple syndromes versus those that may be specific to ADHD.

References

1. Shulman GL, Fiez JA, Corbetta M, Buckner RL, Miezin FM,

Raichle ME et al (1997) Common blood flow changes across

visual tasks. II. Decreases in cerebral cortex. J Cogn Neurosci

9:648–663

2. Fair DA, Cohen AL, Dosenbach NU, Church JA, Miezin FM,

Barch DM et al (2008) The maturing architecture of the brain’s

default network. Proc Natl Acad Sci USA 105:4028–4032

3. Castellanos FX, Margulies DS, Kelly AMC, Uddin LQ, Ghaffari

M, Kirsch A et al (2008) Cingulate-precuneus interactions: a new

locus of dysfunction in adult attention-deficit/hyperactivity

disorder. Biol Psychiatry 63:332–337

Prediction of preschool aggression from parental

ADHD symptoms and child dopamine risk

Tali Farbiash, Andrea Berger, Naama Atzaba-Poria, Rivka Landau,Judith G. Auerbach

Psychology Department, Ben-Gurion University of the Negev,

Beer-Sheva, Israel

Introduction and objective: Children’s aggression is a consequence

of both genetic and environmental factors. For example, children of


123

parents with ADHD are exposed not only to an increased genetic risk

but also to a riskier child-rearing environment (Murray and Johnston

2006). Genes from the dopamine system are related to ADHD

symptoms (Swanson et al. 2007). Moreover, the dopamine system

seems to moderate the relationship between parental influence and the

child’s aggression (Bakermans-Kranenburg and van IJzendoorn

2006). This study investigated the contribution of these two factors,

i.e., the influence of child dopamine risk, the environmental risk

related to the parental level of ADHD symptoms, and the interaction

of these factors on aggression at the age of 4.5 years.

Methods: The sample consisted of 104 4.5-year-old children from the

BIDS longitudinal study. DNA samples were collected from each

child to assess dopamine ADHD risk (DRD4 7 allele and/or DAT1

10/10 alleles). Parental self and spouse reports of ADHD symptoms

were collected using the Conners Adult ADHD Rating Scale (CA-

ARS). The analysis included combined and separate scores of self and

spouse reports of ADHD symptoms. Child aggression at the age of

4.5 years old was assessed using the Child Behavior Checklist

(CBCL) completed by the parents, also using combined and separate

scores of the mother and the father reports.

Results: The regression analyses included demographic variables in

Step 1, independent variables (parental ADHD symptoms, child

dopamine risk) in Step 2, and their interaction in Step 3. The R2

change between Model 2 and Model 1 was significant, indicating

that parental ADHD symptoms and child dopamine risk can predict

child aggression at the age of 4.5 years. Contrary to our hypoth-

eses, no interactions were found. The results derived from parental

self and spouse reports of ADHD symptoms and child dopamine

risk significantly explained 24–32% (multiple R2) of child aggres-

sion variance. Parental ADHD symptoms predicted child

aggression. This was found both for mother and the father symp-

toms, respectively (b = 0.38, p = 0.000; b = 0.30, p = 0.000).

Child dopamine risk significantly predicted aggression when father

ADHD symptoms were included as a predictor (b = 0.21,

p = 0.04) and only marginally predicted aggression when mother

symptoms were included (b = 0.19, p = 0.054). The results

remained significant for inattention symptoms, even when the

ADHD and the aggression reporters were differentiated, using the

separate scores of parental reports.

Discussion: It appears that both parental ADHD symptoms and child

dopamine risk predict child aggression at the age of 4.5 years old,

with parental inattention being the most consistent predictor. Con-

tributions of parental ADHD symptoms, especially inattention, in

addition to the genetic risk seem to reflect a higher risk rearing

environment. Further research is needed, including behavioral mea-

sures, which might replicate the gene–environment interactions found

in previous studies.

Conclusion: Parental inattention exposes children to increased envi-

ronmental risk for aggression at preschool age. This was found

independently of the child’s dopamine risk, emphasizing the impor-

tance of exploring the mediating variables between parental ADHD

and the child’s behavioral outcomes.

References

1. Bakermans-Kranenburg MJ, van IJzendoorn MH (2006) Gene–

environment interaction of the dopamine D4 receptor (DRD4)

and observed maternal insensitivity predicting externalizing

behavior in preschoolers. Dev Psychobiol 48(5):406–409

2. Murray C, Johnston C (2006) Parenting in mothers with and

without attention-deficit/hyperactivity disorder. J Abnormal Psy-

chol 115(1):52–61

3. Swanson JM, Kinsbourne M, Nigg J, Lanphear B, Stefanatos GA,

Volkow N (2007) Etiologic subtypes of attention-deficit/hyper-

activity disorder: brain imaging, molecular genetic and

environmental factors and the dopamine hypothesis. Neuropsy-

chol Rev 17(1):39–59

The importance of focusing on pragmatic language use

in ADHD

Hilde M. Geurts

University of Amsterdam, Department of Psychology, Amsterdam,

The Netherlands

Introduction and objectives: Executive dysfunctions in ADHD do

not exist in isolation and various other cognitive domains have

been studied to understand the etiology of ADHD. However, the

observed language deficits in ADHD, especially in the domain of

pragmatic language use are hardly studied. This is surprising as it

seems that having persistent specific language impairments (SLI) in

the early years of life is an important predictor for future attention

problems (Snowling, Bishop, Stothard, Chipcase, Kaplan 2006).

Moreover, children that do not meet criteria for ADHD but are

known to have pragmatic language deficits such as autism spectrum

disorders (ASD, Geurts et al. 2004) and SLI often do show ADHD

symptoms (Snowling et al. 2006). I will address whether the

pragmatic language problems in ADHD are robust and whether the

presence of ADHD characteristics when having another disorder is

predictive for the severity of pragmatic language problems one

encounters.

Methods: First a literature review of pragmatic language use in

ADHD (Geurts et al. 2010) will be given to show that we need to

think outside the executive functions box when we study ADHD.

Second, the results of two studies will be presented. In study a

children (aged 7–13 years) with ADHD will be compared with chil-

dren with ASD and typically developing controls (TD) on a parent

questionnaire, the Children’s Communication Checklist (CCC-2). In

Study B preschoolers (aged 4–7 years) with ASD will be compared

with preschoolers with SLI and TD preschoolers on this same ques-

tionnaire. In Study B ADHD characteristics will be taken into

account.

Results: The literature review showed that all ADHD studies so far

reported pragmatic language problems in children with ADHD. The

results of Study A indicated that school aged children with ADHD have

similar language profiles as children with ASD. Both groups had rela-

tively more difficulties with pragmatics than with structural language

aspects. The results of Study B indicated that both preschoolers with

ASD and those with SLI show the opposite pattern, thus having rela-

tively more difficulties with structural language aspects than with

pragmatics. Finally, an increase in the presence of ADHD character-

istics of impulsivity in these preschoolers is associated with an increase

in language difficulties, while there is no such relation with inattention.

Conclusion: Pragmatic language use deficits are present in ADHD,

which suggest that these deficits need to be explained by the theo-

retical models of ADHD. Unfortunately most studies, including the

current study, focusing on pragmatic language use in ADHD did not

directly test actual pragmatic language use in children with ADHD

but relied on parent reports. Future studies are needed to determine

the pragmatic language children with ADHD with more direct lan-

guage tests. It also seems useful to evaluate the communication

abilities of children regularly in the course of development and take

ADHD characteristics into account as especially impulsivity measures

are of importance for the observed pragmatic language difficulties in

disorders such as ASD and SLI.

References

1. Geurts HM, Broeders M, Nieuwland MS (2010) Thinking outside

the executive functions box: Theory of Mind and pragmatics in

ADHD. Eur J Dev Psychol

2. Geurts HM, Verte S, Oosterlaan J, Roeyers H, Sergeant JA

(2004) How specific are executive functioning deficits in


123

attention deficit hyperactivity disorder and autism? J Child

Psychol Psychiatry 45(4):836–854

3. Snowling MJ, Bishop DV, Stothard SE, Chipchase B, Kaplan C

(2006) Psychosocial outcomes at 15 years of children with a

preschool history of speech–language impairment. J Child

Psychol Psychiatry 47(8):759–765

Maternal and paternal smoking during pregnancy

and risk for child ADHD: a test for causal associations

Kate Langley1, Jon Heron2, Anita Thapar1

1MRC Centre for Neuropsychiatric Genetics and Genomics,

Department of Psychological Medicine and Neurology, School of

Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK;2Department of Social Medicine, University of Bristol, Canynge Hall,

39 Whatley Road, Bristol BS8 2PS, UK

Introduction and objective: Maternal smoking during pregnancy is

one environmental risk factor which has frequently been observed to

be associated with child ADHD symptoms and disorder. Following

biologically plausible mechanisms through which exposure to

smoking could lead to physiological changes which in turn create

risks for ADHD, it is generally assumed that the association

between ADHD and smoking during pregnancy is causally medi-

ated. However, it is possible that the observed associations are due

to unmeasured genetic or other confounding factors, with some

recent studies supporting this supposition (Thapar et al. 2009).

Indeed, a recent report by the Royal Academy of Medical Sciences

(2007) has highlighted the need to use non-experimental designs to

pick apart the causal pathways from risk factors to disorder. It is

therefore timely to investigate whether maternal smoking during

pregnancy has a true causal influence on offspring ADHD. One way

to address this issue is by comparing the risk from maternal and

paternal smoking during pregnancy (Davey Smith 2008). If there is

a causal intrauterine effect of maternal smoking on child ADHD, no

association should be observed between paternal smoking during

pregnancy and offspring ADHD. However, if the association is due

to genetic or other confounding factors, the risk of offspring ADHD

should be of similar magnitudes for maternal and paternal smoking

during pregnancy.

Methods: We tested this hypothesis in a well characterised longitu-

dinal prospective cohort of UK children, the Avon Longitudinal Study

of Parents and Children (ALSPAC). For n = 5,757 children, mothers

and biological fathers reported on their own smoking behaviour

during pregnancy, whilst ADHD symptoms were assessed using

parent and teacher DAWBA reports at age seven years. Associations

between maternal and paternal smoking during pregnancy were then

compared using regression analyses.

Results: Smoking during pregnancy was reported by 27% of mothers

and 40% of fathers. Maternal smoking during pregnancy was sig-

nificantly associated with offspring ADHD symptoms (b = 0.07,

t = 4.59, p = 5 9 10-6). Paternal smoking during pregnancy was

also associated with increased child ADHD symptoms (b = 0.07,

t = 4.73, p = 2 9 10-6) and diagnosis. These associations remained

when looking only at paternal smoking in the absence of maternal

smoking and did not appear to be the result of exposure to passive

smoking.

Discussion: In a large prospective cohort, we replicated previously

reported associations between maternal smoking during pregnancy

and child ADHD. We also found that paternal smoking during

pregnancy was also associated with child ADHD to a similar

magnitude. These findings suggest, in line with some previous

studies (Thapar et al. 2009), that associations between maternal

smoking during pregnancy and child ADHD may be due to

genetic or other confounding effects, rather than causal intrauterine

effects.

Conclusion: These findings question previously held assumptions

that maternal smoking during pregnancy is a causally mediated risk

factor for ADHD and, in line with a recent paper, (Royal Academy of

Medical Sciences) highlights the importance of using non-experi-

mental designs to pull apart presumed causal associations.

References

1. Thapar A et al (2009) ‘‘Prenatal smoking might not cause

attention-deficit/hyperactivity disorder: evidence from a novel

design’’ biological psychiatry. 66(8):722–727

2. Academy of Medical Sciences Working Group (2007) ‘‘Iden-

tifying the environmental causes of disease: how should we

decide what to believe and when to take action?’’

www.acmedsci.ac.uk

3. Davey Smith G (2008) ‘‘Assessing intrauterine influences on

offspring health outcomes: can epidemiological studies yield

robust findings?’’ Basic Clin Pharmacol Toxicol 102:245–256

Neuropsychological performance and the validity

of DSM-IV ADHD subtypes

Molly Nikolas1, Joel T. Nigg2

1Department of Psychology, Michigan State University, East Lansing,

USA; 2Department of Psychiatry, Oregon Health and Science

University, Portland, USA

Introduction and objective: Neuropsychological theories of atten-

tion-deficit/hyperactivity disorder (ADHD) serve an important role in

etiological investigations of the disorder by linking observable

behavioral symptoms with underlying neural processes and mecha-

nisms (Sonuga-Barke 2005). Additionally, measures of

neuropsychological performance, including executive functioning,

may also provide one fruitful method of evaluating the validity of the

ADHD subtypes. Identification of specific domains or deficits that

differentiate the ADHD-Combined (ADHD-C) and ADHD-Predom-

inately Inattentive (ADHD-PI) subtypes may be crucial for refinement

of classification systems as well as for advancing etiological process

theories. However, past work regarding subtype differences in neu-

ropsychological performance has been mixed, with some studies

finding subtype-specific deficits (or subtype 9 gender specific defi-

cits) while others have failed to show differences between ADHD

subgroups (Nigg et al. 2002). Additionally, symptom profile hetero-

geneity within the ADHD-PI subtype (i.e., differences in overall level

and history of hyperactivity) may also be obscuring potential differ-

ences with the combined subtype. The goal of the current project was

to examine potential ADHD subtype differences across multiple

domains of neuropsychological functioning, including response

inhibition, vigilance, interference control, cognitive set-shifting, and

working memory. Further, we also investigated whether differences in

current hyperactive symptoms and history of hyperactivity influenced

neuropsychological performance within the ADHD-PI group

specifically.

Methods: Participants were 464 youth ages 6–17 years (M = 10.8,

SD = 2.4 years, 55.0% male) and were recruited from the local

community via mass mailings to families within the local school

district, advertisements, and through local clinics. Families completed

a multi-stage, multi-informant assessment process, including broad-

band rating scales and semi-structured interviews, to determine


123

http://www.acmedsci.ac.uk

ADHD cases and non-ADHD controls among those who volunteered.

Teachers also completed standardized behavioral rating scales. Cur-

rent and lifetime symptom data as well as treatment history were then

presented to a diagnostic team consisting of a board-certified child

psychiatrist and licensed child-clinical psychologist, who arrived

independently at ADHD subtype and comorbid diagnoses. Agreement

rates for these professionals was acceptable (j = 0.89). At stage 2,

youth completed a standardized neuropsychological testing battery

(after an appropriate wash-out period if taking stimulant medication)

consisting of the following tests and domains of functioning: Stop

Task (response inhibition, response variability), WISC-IV digit span

(verbal working memory), continuous performance task (vigilance),

spatial span (visual working memory), DKEFS Color-Word Inter-

ference (interference control), and DKEFS Trailmaking (cognitive

set-shifting). The final sample consisted of 213 control youth and 251

ADHD youth (107 Primarily Inattentive, 7 Primarily Hyperactive, and

137 Combined subtype).

Results: Regression models were first examined to determine group

differences in performance among all ADHD versus control youth

as well as between the ADHD subtypes specifically (ADHD-C vs.

ADHD-PI). Orthogonal contrast codes (i.e., ADHD vs. Control,

ADHD-PI vs. ADHD-C) were simultaneously entered into as pre-

dictors of test performance in addition to covariates (sex, age).

Results indicated significant group differences between ADHD and

control youth for all neuropsychological domains, which remained

significant after correction for multiple tests. However, subtype

differences only persisted for measures of response inhibition

(p = 0.018), response variability (p = 0.03), vigilance (p = 0.004),

and interference control (p \ 0.001), with the combined subtype

performing worse in all domains. We next further divided the

ADHD-PI group into two classes: a ‘‘pure’’ inattentive class (i.e., 2

or fewer current hyperactive symptoms and no history of ADHD-C,

n = 66) and a ‘‘mild’’ combined class (i.e., 3 or more current

hyperactive symptoms or history of past ADHD-C diagnosis,

n = 44). The executive measures failed to differentiate these two

classes from each other (all p [ 0.21). Importantly however, the

ADHD-PI ‘‘pure’’ class demonstrated significantly slower perfor-

mance than the ‘‘mild-Combined’’ class on overall measures of

speed (DKEFS Color Naming p = 0.002, DKEFS Trails Motor

Speed p = 0.008), indicating that overall processing speed (and not

executive ability) may contribute to heterogeneity among the

ADHD-PI subtype.

Discussion and conclusion: Study results indicated that measures of

response inhibition, response variability, vigilance, and interference

control may distinguish the ADHD-C and ADHD-PI subtypes from

each other. These findings generally suggest that these particular

domains of executive functioning and their underlying neural pro-

cesses may differentially contribute to inattention versus

hyperactivity-impulsivity. Importantly, however, executive measures

failed to account for heterogeneity within the ADHD-PI subtype.

Instead, overall neural processing speed may account for differences

among those with purely inattentive symptoms versus those with mild

or subthreshold-combined subtype symptom profiles. Importantly,

however, the current study accounted for lifetime symptom history

when assigning diagnosis, which may have contributed to a more

homogenous ADHD-PI group compared to other studies. Future work

investigating the validity of subtype differences as well as heteroge-

neity within the ADHD-PI group will remain critical for informing

the development of new classification paradigms and etiological

theories of ADHD.

References

1. Nigg JT, Blaskey LG, Huang-Pollock C, Rappley MD (2002)

Neuropsychological executive functions and DSM-IV ADHD

subtypes. J Am Acad Child Adolesc Psychiatry 41:59–66

2. Sonuga-Barke EJS (2005) Causal models of attention-deficit/

hyperactivity disorder: from common simple deficits to multiple

developmental pathways. Biol Psychiatry 57:1231–1238

Neurofeedback for children with attention-deficit/

hyperactivity disorder: clinical and neurophysiological

results of a randomised controlled trial

Petra Studer1, Holger Gevensleben2, Susanne Wangler1,Aribert Rothenberger2, Gunther H. Moll1, Hartmut Heinrich1,3

1Department of Child and Adolescent Mental Health, University of

Erlangen, Erlangen, Germany; 2Child and Adolescent Psychiatry,

University of Gottingen, Gottingen, Germany; 3Heckscher-Klinikum,

Munich, Germany

Introduction and objective: Neurofeedback is a neuro-behavioural,

computer-assisted training which could become an important treat-

ment module for children with attention-deficit/hyperactivity disorder

(ADHD). In a multisite randomised controlled study, we evaluated

clinical and neurophysiological effects of a neurofeedback training

compared to a control training.

Methods: The sample included 102 children with ADHD, aged 8–12,

who either performed a neurofeedback training or a computerised

attention skills training (randomised group assignment). The training

programs comprised 36 sessions within two blocks of about 4 weeks

each. The neurofeedback training consisted of both a theta/beta

training and a slow cortical potentials (SCP) training. Pre-training,

intermediate and post-training assessment comprised several behav-

iour rating scales (e.g. the German ADHD rating scale, FBB-HKS)

and neurophysiological measurements (EEG, event-related

potentials).

Results: For both parent and teacher ratings, the neurofeedback

training was superior to the control training. The effect size was 0.60

for the FBB-HKS total score (parent ratings, primary outcome mea-

sure). In the resting EEG the neurofeedback group showed a reduced

theta activity after the end of training. In addition, EEG measures

recorded at baseline as well as changes of EEG parameters from pre

to post training were related to the clinical outcome. Furthermore,

SCP training was associated with an increase of the contingent neg-

ative variation in a cued attention test. Contrary to our expectations no

increase of the P300 amplitude was found for the theta/beta training

group. Behavioural improvements induced by neurofeedback

remained stable at 6-month follow-up.

Discussion: The superiority of the neurofeedback training to the

computerised attention skills training as well as the stability of the

effects at 6-month follow-up indicate the clinical efficacy of neuro-

feedback in children with ADHD. The neurophysiological effects

could reflect correlates of a successful training.

Conclusion: Neurofeedback can be considered as a clinically effec-

tive method for the treatment of children with ADHD. Future studies

should examine how to optimise a neurofeedback training and how to

integrate it into a multimodal treatment program for children with

ADHD.

Funded by the German Research Foundation (HE4536/2, MO 726/2,

RO 698/4).

References

1. Gevensleben H, Holl B, Albrecht B, Vogel C, Schlamp D, Kratz

O, Studer P, Rothenberger A, Moll GH, Heinrich H (2009) Is

neurofeedback an efficacious treatment for ADHD? A random-

ised controlled clinical trial. J Child Psychol Psychiatry

50(7):780–789


123

2. Gevensleben H, Holl B, Albrecht B, Schlamp D, Kratz O, Studer

P, Wangler S, Rothenberger A, Moll GH, Heinrich H (2009)

Distinct EEG effects related to neurofeedback training in children

with ADHD: a randomized controlled trial. Int J Psychophysiol

74:149–157

Genome wide association analysis of the volume

of subcortical brain structures in healthy individuals

reveals genes involved in attention deficit hyperactivity

disorder

Alejandro Arias Vasquez1,2, Mark Rijpkema3, Joris Veltman2,Han Brunner2, Guillen Fernandez3, Barbara Franke1,2

1Department of Psychiatry, Donders Institute for Brain, Cognition and

Behavior, Nijmegen, The Netherlands; 2Department of Human

Genetics, Radboud University Nijmegen Medical Center, Nijmegen,

The Netherlands; 3Donders Institute for Brain, Cognition and

Behavior, Donders Center for Cognitive Neuroimaging, Nijmegen,

The Netherlands

Introduction: Attention deficit hyperactivity disorder (ADHD) is a

highly heritable disease, its etiology is complex and combinations

of genes interacting with each other and with environmental factors

contribute to its etiology. However, still only a small part of the

genetic component of this disorder can be explained. The generally

small effect sizes of genetic risk factors have hampered the iden-

tification of genes predisposing to ADHD. With the recent advent

of genome-wide association studies (GWAS), the identification of

new genes for multifactorial diseases and traits has become very

successful. It has been proposed that endophenotypes, defined as

heritable traits that are associated with a disorder, can be more

suitable for detecting risk genes for complex disorders than the

clinical phenotypes because they are genetically less complex by

being etiologically closer to disease genes. Endophenotypes,

besides being more directly affected by genetic variation, will show

association in carriers of risk alleles even if these do not have any

clinical diagnostic characteristics. This makes these traits obser-

vable in healthy individuals, independent of the influences of

disease and treatment. Brain imaging has identified both structural

and functional types of Abnormalities in ADHD and an ADHD

meta-analysis on brain structural imaging confirms that several

structures of the brain show consistent volume reductions in

patients relative to controls. ADHD-related brain structures may

serve as suitable endophenotypes for this disorder providing

superior power in genome-wide gene finding studies compared to

clinical phenotypes. This endophenotype hypothesis is supported by

results of recent meta-analyses showing strong effects of genetic

variation in the catechol-O-methyltransferase gene (COMT) on

prefrontal activation and in the serotonin transporter gene (5-

HTTLPR) on the activation of the amygdala, proving the power of

genetic studies using this approach. In this study, we aimed to test

the hypothesis that identifying genes related to variance of specific

regional brain volume endophenotypes in healthy individuals serves

to identify risk genes for ADHD.

Methods: The Brain Imaging Genetics study (BIG), established in

2007 as a collaboration of the Donders Center for Cognitive Neuro-

imaging (DCCN) and the department of Human Genetics of the

Radboud University Nijmegen Medical Center, includes DNA and

neuroimaging data of [1,400 healthy individuals (mean age 28,

42.2% male) with structural magnetic resonance imaging (sMRI) in

1.5 or 3 T scanners. The gray/white matter density of the whole brain

and the volume of individual subcortical structures is quantified by

the automated and unbiased techniques of whole brain voxel-based

morphometry and volumetry. ADHD candidate brain volumes

include: basal ganglia, hippocampus, amygdala, total brain, grey and

white matter volumes. DNA was extracted from saliva using the

Oragene DNA sample collection kit. Genotypes were available from

Affymetrix SNP 6.0 arrays. We selected SNPs with minor allele

frequency (MAF) C 0.05 and Hardy–Weinberg equilibrium (HWE) pvalue C 1.0E26. In order to increase the coverage of the genome, we

imputed the SNP information provided by hapmap 1 and 2 projects.

Association was performed using the linear regression option in

mach2qtl. The analysis was adjusted by age, gender, total brain vol-

ume and field strength.

Results: For the basal ganglia (nucleus accumbens, caudate nucleus,

globus pallidus), SNPs located in the GPM6A and RGS6 genes

showed p values B 10E206 with nucleus accumbens volume. For

caudate nucleus volume, four SNPs showed p values B 10E206, two

located on the DLGAP2 gene. Five SNPs showed p val-

ues B 10E206 with globus pallidus volume. From these, two were

located on the PDGFRL gene, one on the PSD3 and one on the BAI3.

Other interesting findings include 14 SNPs with association p val-

ues B 10E206 with hippocampus volume from which a haplotype

block of seven SNPs is located on the PCP4 gene. SNPs in the gene

CDH13 showed p values with hippocampus volume (pvalue B 10E205). Amygdala results include p values B 10E206 for

SNPs on the LECT1 and the CDH13 genes. Analysis of grey matter

volume yielded SNPs with association p values B 10E206 located on

the ARHGEF10 gene. The best hits of the white matter analysis were

two SNPs with association p values B 10E206 located in intergenic

region on chromosome 4 at 28.4 kb upstream from the RGS12 gene.

Interestingly, CDH13 again showed an association with this trait (pvalues B 10E205).

Discussion and conclusion: We have presented the first GWAS for

ADHD-related brain volume endophenotypes. Genome-wide sig-

nificant effects elude detection for our selected traits, suggesting

that the effect sizes influencing the variance of brain volumes are

likely to be small, or the heritability may be accounted for by rare

variants of greater effect sizes not detected by our approach. Our

results include a number of promising regions, for which replica-

tion is an essential next step. Interestingly, one of the analyses

implicated the CDH13 gene in hippocampus, amygdala and white

matter volumes. CDH13 lies under the only significant linkage

peak derived from a meta-analysis of 7 ADHD linkage studies and

is among the top-findings of the biggest available ADHD GWAS

meta-analysis. It has also been implicated in substance use disor-

ders, which frequently co-occur with ADHD. Interesting new

candidate genes for ADHD found in this study include (among

others) the BAI3 gene associated with globus pallidus volume and

the PCP4 gene, associated with hippocampus volume. Globus

pallidus is a major element of the basal ganglia system which has

been found involved in ADHD. Hippocampus is known to be

involved in attentional processes such as visuospatial working

memory and in modulating executive functions. Disturbances in

these domains belong to core symptoms of ADHD. In conclusion,

our findings represent an important leap forward in the search for

candidate genes for ADHD (and other psychiatric disorders) by

applying ‘‘reverse genetics’’ using neuroimaging-derived endophe-

notypes from healthy individuals which can be used to further our

understanding of the basis of brain structure and function providing

superior power to define the effects of genetic variants involved in

both health and disease phenotypes.


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Poster Abstracts

Poster Sessions A: Diagnosis,Evaluation and Treatment

Parental and children rating of sleep in boys

with attention deficit/hyperactivity disorder

F. Aggio1, M. Saccani1, E. Boin1, P. Olgiati1, A. Frisoni1,G. Galimberti1, E. Buzzi1, C. Lenti1

1Department of Child and Adolescent Psychiatry, San Paolo Hospital,

University of Milan, Milan, Italy

Introduction and objective: Sleep problems have been associated

with ADHD. This study describes sleep behaviour of ADHD children

and examines the relationship between measured sleep patterns and

psychiatric symptoms.

Method: The study included 44 boys aged 7–13 years, 17 ADHD and

27 healthy. Sleep difficulties were rated using The Children’s Sleep

Habits Questionnaire and The Sleep Self-report. Parents completed the

CBCL.

Results: ADHD group showed difficulties on parasomnias and sig-

nificantly higher scores on the Sleep Self Report. Using the CBCL,

participants with sleep problem in the ADHD group, were signifi-

cantly more likely to exhibit affective problems. Comorbid ODD

appeared not to have an added effect on problematic behaviour

around bedtime.

Discussion: The results support an increased overall prevalence of

sleep disturbances in ADHD children, although we found discrep-

ancies between parent and child reports. The correlations between

sleep problems and internalizing symptomatology suggest the

importance of screening all children with sleep problems for anxious-

depressive symptoms.

Conclusions: This study indicates a need for screening ADHD chil-

dren for sleep problems and obtaining information about sleep from

parents and from children.

References

1. Cortese S, Faraone SV, Konofal E, Lecendreux M (2009) Sleep

in children with attention-deficit/hyperactivity disorder: meta-

analysis of subjective and objective studies. J Am Acad Child

Adolesc Psychiatry 48(9):894–908

2. Owens JA (2009) A clinical overview of sleep and attention-

deficit/hyperactivity disorder in children and adolescents. J Can

Acad Child Adolesc Psychiatry 18(2):92–102

3. Owens JA, Maxim R, Nobile C, Mcguinn M, Msall M (2000)

Parental and self-report of sleep in children with attention deficit/

hyperactivity disorder. Arch Pediatr Adolesc Med 154: 549–555

Evaluation of maternal parenting behaviour

and maternal depressive symptomatology in boys

with attention deficit/hyperactivity disorder

and oppositional defiant disorder

F. Aggio1, M. Saccani1, P. Olgiati1, A. Frisoni1, G. Galimberti1,E. Buzzi1, C. Lenti1



Introduction and objective: ADHD is associated to varying degrees

with disrupted parent–child relationships particularly when comorbid with

CD. The study compares parenting maternal behaviour of ADHD and

ADHD + ODD children; evaluates the correlations between maternal

parenting, depressive traits and children’s features; examines the relation-

ship of these dimensions with locus of control, parenting efficacy and stress.

Method: The study included 39 mothers: 12 control group, 12 ADHD

group, 15 ADHD + ODD group. All mothers completed question-

naires pertaining to: child behaviour, maternal depressive traits and

maternal cognitions about parenting behaviour.

Results: We found higher maternal depression, parenting stress, lax

parenting and significant correlations between over-reactive parenting

and depression, external LCB, sense of competence and parental

stress in the ADHD + ODD group.

Discussion: Depressed ADHD + ODD mothers show negative cog-

nitions about their parental role and parenting strategies characterized

by hostility and conflicted interactions.

Conclusions: Mothers of ADHD + ODD children have more risk

factors that are involved in the development of aggression and

oppositional defiant behaviour. ADHD families may benefit from an

expanded version of parent training that includes sessions directly

targeting parental affective and cognitive factors.

References

1. Gerdes AC, Hoza B, Arnold LE, Pelham WE, Swanson JM,

Wigal T, Jensen PS (2007) Maternal depressive symptomatology

and parenting behavior: exploration of possible mediators. J

Abnorm Child Psychol 35:705–714

2. Johnston C, Mash EJ (2001) Families of children with attention-

deficit/hyperactivity disorder: review and recommendations for

future research. Clin Child Family Psychol Rev 4(3)

3. Cunningham CE (2007) A family-centered approach to planning

and measuring the outcome of interventions for children with

attention-deficit/hyperactivity disorder. J Pediatric Psychol

32(6):676–694

Does paediatric bipolar disorder commonly occur

in attention deficit hyperactivity disorder? A UK study

Sharifah Shameem Agha1,2, Amani Hassan 1,2, Kate Langley2,Anita Thapar2

1Cwm Taf NHS Trust, Aberdare, UK; 2MRC Centre for

Neuropsychiatric Genetics and Genomics, Department of Psychological

Medicine and Neurology, Cardiff University, Cardiff, UK

Introduction and objective: Some research suggests that children

with ADHD are at higher than expected risk of Paediatric Bipolar

Disorder (PBD) [1]. No studies have examined the prevalence of PBD

in a UK sample of children with ADHD. To examine the prevalence of

PBD in children diagnosed with ADHD or Hyperkinetic disorder [2].

Methods: 200 participants with ADHD (170 males, 30 females) aged

6–18 years, mean age = 11.15 years, SD = 2.95, were recruited.

Psychopathology including ICD 10 and DSM IV symptoms and

diagnoses of PBD was assessed using the Child and Adolescent

Psychiatric Assessment (CAPA) research diagnostic interview. Rates

of PBD symptoms and diagnoses are reported. Family history of

bipolar disorder in parents and siblings was also recorded.

Results: Only one child (0.5%), male aged 9 years, met diagnostic

criteria for ICD 10 Hypomania and DSM IV Bipolar Disorder Not

Otherwise Specified.

Discussion: PBD was uncommon in our sample. This varies from

findings of some other studies and this may be explained by sample

selection, age or differences in diagnostic practices [3].


123

Conclusion: In a UK sample of children with ADHD, the diagnosis of

PBD was uncommon.

AcknowledgmentsWellcome Trust.

References

1. Biederman J, Faraone S, Mick E, Wozniak J, Chen L, Ouellette C

et al (1996) Attention-deficit hyperactivity disorder and juvenile

mania: an overlooked comorbidity? J Am Acad Child Adolesc

Psychiatry 35(8):997–1008

2. Stringaris A, Santosh P, Leibenluft E, Goodman R (2009) Youth

meeting symptom and impairment criteria for mania-like epi-

sodes lasting less than four days: an epidemiological enquiry. J

Child Psychol Psychiatry

3. Kent L, Craddock N (2003) Is there a relationship between

attention deficit hyperactivity disorder and bipolar disorder? J

Affect Disord 73(3):211–221

Validity of the DSM-IV factor structure of ADHD

in young adults

Dieter Baeyens1,2, Lotte Van Dyck1, Marina Danckaerts2

1CODE Lessius, Research Group Developmental Disorders, Lessius

University College, Katholieke Universiteit Leuven Association,

Sanderusstraat 45, 2018 Antwerp, Belgium; 2University Psychiatry

Centre, Katholieke Universiteit Leuven, Department of Child and

Adolescent Psychiatry, UZ Leuven, Herestraat 49, 3000 Leuven,

Belgium

Introduction and objective: DSM conceptualization of ADHD

portrays inattention (IA) and hyperactivity/impulsivity (H/I) as two

separate dimensions. We set out to determine whether the current

factor structure is applicable to young adults.

Methods: Parent and self reports on DSM-IV ADHD symptoms were

obtained for 672 (280 M/392 F) adults (16–25 years old) from a

community-based sample. Confirmatory (CFA) and exploratory

(EFA) factor analysis were used to examine the data structure.

Results: CFA for parent and self-reports revealed that single (IA/H/I),

two (IA + H/I) or three-factor (IA + H + I) models do not meet the

minimum thresholds for goodness-of-fit. Data fit the three-factor

model best. EFA indicates that self report data support a four-factor

structure (IA, H, I and ‘‘emotional restlessness’’) whereas parent

ratings reveal the current DSM structure.

Discussion: CFA indicates that ADHD symptoms in young adults are

best—but not adequately—described by a three-factor model. Further

evidence for this was found in EFA on self report data which suggests

that more differentiation is needed.

Conclusion: These findings highlight that the current DSM taxonomy

of ADHD does not fully account for the complex nature of adult ADHD.

Preschool disruptive behaviour disorders, ADHD

and dysregulation

Bothild Bendiksen1, Pal Zeiner1, Heidi Aase2,and the ADHD Project Group1,2

1Oslo University Hospital, Ullevaal, Oslo, Norway; 2Norwegian

Institute of Public Health, Division of Mental Health, Department of

Adult Mental Health, Oslo, Norway

Introduction and objective: Studies in preschool age children have

shown that more than 50% of patients with ADHD also have

comorbid disruptive behaviour disorders (DBD) [1]. Hyperactive-

impulsive ADHD and disruptive disorder symptoms may be asso-

ciated with dysregulation of emotions, sleep, and sensory stimuli

[2, 3].

Methods: Population based birth cohort design. Clinical assessment.

About 600 children aged 36–44 months, recruited from the Mother

and Child Cohort Study (MoBa) [3].

Preliminary results: Preliminary analyses of a subset of 438 chil-

dren showed that symptoms of disruptive behaviour disorders were

found in 40% of the total sample, where of 40% also had ADHD at

either clinical or subthreshold levels. Dysregulation of emotions,

sleep, or sensory stimuli is identified in more than 50% of the

children, and there is a significant overlap with ADHD and DBD

symptoms.

Discussion: The nature of the co-occurrence of overlapping symp-

toms of disruptive behaviour disorders, dysregulation, and ADHD

needs further exploration.

Conclusion: The preliminary results of the ADHD-study show that

there is an overlap of children with ADHD, DBD, and dysregulation.

Further analyses will be presented at the conference in May.

References

1. Egger HL, Angold A (2006) Common emotional and behavioral

disorders in preschool children: presentation, nosology, and

epidemiology. J Child Psychol Psychiatry Allied Discipl 47:313–

337

2. Martel M (2009) Research review: a new perspective on

attention-deficit/hyperactivity disorder: emotion dysregulation

and trait models. J Child Psychol Psychiatry Allied Discipl

50:1042–1051

3. Gouze KR, Hopkins J, LeBailly SA, Lavigne JV (2009) Re-

examining the epidemiology of sensory regulation dysfunction

and comorbid psychopathology. J Abnormal Child Psychol

37:1077–1087

Are attachment disorganization and inhibition

independent predictors of symptoms of ADHD,

externalizing problem behaviors and callous

unemotional traits?

Gunilla Bohlin, Lisa Thorell, Lilianne Eninger, Carin Brocki

Department of Psychology, Uppsala University, Uppsala, Sweden

The aim of the present study was to investigate whether attachment

insecurity, focusing on disorganized attachment, and the EF compo-

nent inhibition, assessed at age 5 are independently longitudinally

related to ADHD symptoms, externalizing problem behaviors and

callous unemotional traits as rated by parents and teachers. The

sample consisted of 60 children with an oversampling of children

with high levels of ADHD symptoms. Attachment was evaluated

using an Attachment Doll play procedure in which children complete

a story that is started by the experimenter and the content of which is

intended to activate the attachment system. Inhibition was measured

with three different tasks. The results showed that disorganized

attachment and inhibition were both longitudinally related to all three

outcome variables, but independent relations were only obtained for

externalizing behaviours. ADHD symptoms were independently

explained only by inhibition, and callous unemotional traits only by

disorganized attachment. The results are discussed regarding the

construct of disorganization and to what extent poor inhibitory control

is reflected in the production of stories fulfilling coding criteria for

disorganization.


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Understanding the universal burden of adult ADHD:

a seven country perspective

Meryl Brod1, Rahul Sasane2, Philip Asherson3

1The Brod Group, Mill Valley, CA, USA; 2Shire Development Inc.,

Wayne, PA, USA; 3MRC Social, Genetic and Developmental

Psychiatry Centre, Institute of Psychiatry, Denmark Hill, London, UK

Objectives: This study aimed to better understand similarities and

differences in the description of adult ADHD in countries with a

spectrum of diagnostic and treatment perspectives.

Methods: 14 focus groups in 7 countries (US, Canada, UK, The

Netherlands, Italy, France and Germany) followed the same interview

guide exploring diagnosis, treatments, and impact of ADHD on daily

life, functioning and well-being of adult patients.

Results: 108 patients participated in the focus groups. Mean age

was 36 years, with 47% female. Mean time since diagnosis was

8 years (range 0–46 years) and 32% diagnosed with ADHD as

children. Lifetime average number of ADHD medications was 1.7,

with 55% currently treated with prescription ADHD medication.

All groups reported the universal symptoms of hyperactivity,

inattention, disorganization, and impulsivity, often resulting in

destructive behaviors. 4 areas of functioning and well-being were

impacted by ADHD regardless of country, or perspective: symptom

presentation, impact on daily life, social functioning and psycho-

logical health.

Conclusion: The burden of adult ADHD appears to be universal and the

experience and presentation of symptoms is not culturally dependent.

Supported by funding from Shire Development, Inc.

An examination of the sources of rater bias in parental

ratings on ADHD symptoms

R. Campos-Pinto1, A. Wood1, R. Plomin1, P. Asherson1, F. Rijsdijk1,J. Kuntsi1

1MRC SDGP Centre, Institute of Psychiatry, King’s College London,

London, UK

Introduction and objective: Many twin studies on parental ratings of

ADHD symptoms have reported very low dizygotic (DZ) correlations,

attributable to a contrast effect. The evidence suggests this reflects a

form of rater bias, rather than actual behavioural differences. Contrast

effects are not universally found in parental ratings. However, with

the exception of rating-scale characteristics, we know little about the

factors that contribute to the contrast effects in parental ADHD

ratings.

Methods: Using data from the Twins’ Early Development Study we

aim to explore a range of socio-demographic factors that potentially

contribute to contrast effects in parental ratings (ethnicity, SES, child

gender, and family size) of ADHD symptoms.

Results: We will report findings from analyses testing for the pres-

ence of significant larger DZ phenotypic variance, suggestive of

contrast effects.

Discussion: There are implications for research if the accuracy of the

most common source of data on ADHD symptoms—parental rat-

ings—is potentially compromised due to rater bias.

Conclusion: A greater understanding of the underlying mechanisms

of contrast effects will inform accurate measurement of ADHD

symptoms and phenotypic definition, crucial for the success of

molecular genetic investigations.

Prevention of childhood attention-deficit-/hyperactivity

disorder (ADHD) in the context of parental disorders

Hanna Christiansen1, Jana Anding1, Miriam van der Ven1,Bernhard Kis2, Jens Wiltfang2, Jennifer Uekermann2, Bernd Rohrle1

1Philipps-University Marburg, Department of Clinical Psychology,

Marburg, Germany; 2University of Duisburg-Essen, Department of

Psychiatry and Psychotherapy, Essen, Germany

Introduction and objective: Transgenerational transmission of

mental illness is one of the most significant causes of psychiatric

morbidity. Evidence for an elevated risk has been found across the

whole diagnostic spectrum of parental psychiatric disorders. The four-

to eightfold increase in risk for ADHD in first degree relatives of

cases points to the importance (economic and healthcare) of pre-

ventive family interventions for this group.

Methods: Systematic literature search to identify preventive inter-

ventions for families with mental disorders and especially ADHD.

Pilot study on a preventive cognitive-behavioral family intervention

with nine participating ADHD families.

Results: No studies of the children of parents with ADHD were

found. Prior to study participation, families with parental ADHD

received overall insufficient therapeutic support. Pilot study satis-

faction was high for both parents and children and increases in key

target features were obtained.

Discussion: In the absence of investigations and high quality inter-

ventions families with parental ADHD remain severely and multiply

impaired.

Conclusion: There is a major need for high quality studies on pre-

ventive interventions for children of parents with ADHD.

Keywords: Preventive intervention, Parental mental illness, Adult

ADHD

Validation of the German version of the Conners Adult

ADHD Rating Scales (CAARS)

Hanna Christiansen1, Bernhard Kis2, Oliver Hirsch3,Alexandra Philipsen4, Melanie Henneck5, Alexander Panczuk5,Reinhard Pietrowsky5, Johannes Hebebrand6,Benno G. Schimmelmann7



Psychiatry and Psychotherapy, Essen, Germany; 3Philipps-University

Marburg, Department of General Practice/Family Medicine, Marburg,

Germany; 4University of Freiburg, Department of Psychiatry and

Psychotherapy, Freiburg, Germany; 5University of Dusseldorf,

Institute of Experimental Psychology, Department of Clinical

Psychology, Dusseldorf, Germany; 6University of Duisburg-Essen,

Department of Child and Adolescent Psychiatry and Psychotherapy,

Essen, Germany; 7University Hospital of Child and Adolescent

Psychiatry, Bern, Switzerland

Introduction and objective: Instruments for diagnosing attention-

deficit/hyperactivity disorder (ADHD) in childhood are well vali-

dated and reliable, but diagnosis of ADHD in adults remains

problematic. To date the Conners Adult ADHD Rating Scales

(CAARS) are the international standard for questionnaire assess-

ment. The current study is the first to evaluate a German version of

the CAARS.


123

Methods: We recruited 850 healthy German subjects to fill out the

CAARS and questions on socio-demographic variables. Explorative

(EFA) and confirmative factor analyses (CFA) were conducted to

obtain factor structure and to replicate the original American-model.

Results: EFA of the German sample results in a six factor solution

explaining 52% of the variance; CFA based on the original American-

model showed a high model-fit. Analyses of normative data showed

significant influences of age, gender, and education level on the

emerging subscales.

Discussion: EFA results in different factors for the German sample,

but CFA shows such a high model fit that the use of each instrument

in its cultural context is justified with comparable ratings of

symptomatology.

Conclusion: The German version of the CAARS is a cross-culturally

valid instrument for the assessment of adult ADHD.

Keywords: Attention-deficit/hyperactivity disorder, Adult ADHD,

Adult ADHD assessment; Diagnostic issues, Conners Adult ADHD

Rating Scales (CAARS)

Insights in the comorbidity between ADHD and obesity:

the role of inflammatory factors

Samuele Cortese1,2, Erika Comencini1, Marco Angriman1,3,Claudio Maffeis4

1Child Neuropsychiatry Unit, Verona University, Verona, Italy;2Child and Adolescent Psychiatry Unit, University Hospital

Clocheville, Tours, France; 3Child Neuropsychiatry Unit, Bolzano,

Italy; 4Regional Center for Juvenile Diabetes, Department of Mother

and Child, Biology-Genetics, Section of Pediatrics, University of

Verona, Verona, Italy

Introduction: The mechanisms underlying the newly described

comorbidity between ADHD and obesity remain to be elucidated [1].

Preliminary hypotheses suggest that alterations of inflammatory fac-

tors may increase the risk for ADHD [1]. A pro-inflammatory state

has been reported in obese children.

Objective: To assess the prevalence of ADHD and the correlation

between ADHD symptoms severity and IL-6, IL-10, and TNFa serum

levels in obese children.

Methods: Subjects: Obese children (BMI [ 95th percentile) referred

to an outpatient unit. Tools: Semi-structured Kiddie-SADS-PL;

Conners Parents (CPRS-R:S) and Teachers Rating Scales Revised

(CTRS-R:S). IL-6, IL-10, and TNFa serum levels were determined

with the ELISA method.

Results: 82 subjects (M = 41; 10.7 ± 2.1 years) have been included.

16% (13/82) present with ADHD. To date, inflammatory factors

measures are available for 49 subjects. IL-10 levels were significantly

correlated with H–I subscale scores of the CPRS-R:S (p = 0.003), as

well as with H–I subscale scores of the CTRS-R:S (p = 0.019).

Conclusions: The prevalence of ADHD in obese children is signifi-

cantly higher than expected according to population-based rates. High

levels of IL-10 might contribute to the pathophysiology of hyperac-

tive-impulsive symptoms in obese children.

Reference

1. Cortese S, Angriman A, Maffeis C, Isnard P, Konofal E,

Lecendreux M, Purper-Ouakil D, Vincenzi B, Dalla Bernardina

B, Mouren MC (2008) Attention-deficit/hyperactivity disorder

(ADHD) and obesity: a systematic review of the literature. Crit

Rev Food Sci Nutr 48(6):524–537

Somatic conditions beyond core symptoms: is ADHD

a multifaceted medical condition?

Samuele Cortese

Child and Adolescent Psychiatry Unit, University Hospital

‘‘Clocheville’’, Tours, France

Introduction/objectives: Preliminary evidence suggests that somatic

conditions are significantly associated with ADHD [1]. The aims of

this work are: (1) To systematically review this evidence; (2) To

assess the prevalence of somatic conditions in a clinical sample of

ADHD children.

Methods:

1. Systematic literature review (Pubmed, PsycINFO 1970–2010).

2. Chart review of 142 outpatient medication-naıve ADHD children.

Results:

1. The relationship between ADHD and sleep, obesity, asthma, and

allergy was assessed in 24, 13, 5, and 6 studies, respectively.

2. 42% of subjects had significant sleep impairment; 31% had

overweight/obesity (national prevalence: 16%); 30% had at least

one other current somatic condition. There was no significant

association between ADHD severity/type and somatic conditions.

Discussion: Methodological issues limit the conclusions of most of

available studies. Our study addressed some previous limitations

(including small sample size and mixed medication status).

Conclusion: Evidence on the association between ADHD and

somatic conditions is increasing but still limited by small studies.

Given the considerable public health interest of this topic, further

research on the underlying neurobiological mechanisms and on evi-

dence-based treatment strategies is needed.

References

1. Cortese S, Castellanos FX (2010) Dopamine reward pathway in

adult ADHD. JAMA 303:233–234

2. Bruni O, Ottaviano S, Guidetti V, Romoli M, Innocenzi M,

Cortesi F, Giannotti F (1996) The Sleep Disturbance Scale for

Children (SDSC). Construction and validation of an instrument to

evaluate sleep disturbances in childhood and adolescence. J Sleep

Res 5:251–261

Psychopathological comorbidity among ADHD children

with and without learning disabilities as reported

by parents

D’Elia Lidia, Napolitano Carmen, Vicari Stefano

Introduction and objective: Attention deficit hyperactivity disorder

(ADHD) often meets criteria for learning disorder (LD): ADHD with

LD are at greater risk for psychopathological disorders. The aim is to

value possible psychopathological comorbidity among ADHD chil-

dren with and without LD.

Methods: The sample is divided in two groups (ADHD with and

without LD). To assess behavioral problems we use the Child

Behavior Checklist for ages 6–18.

Results: The two groups displayed externalizing problems.


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Discussion: Our finding do not consistently differentiate between two

groups.

Conclusion: This study lays the foundation for continued research

into the comorbidities of children with ADHD.

References

1. Oram Cardy JE, Tannock R, Johnson AM, Johnson CJ (2009)

The contribution of processing impairments to SLI: insights from

attention-deficit/hyperactivity disorder. J Commun Disord [Epub

ahead of print]

2. Pisecco S, Baker DB, Silva PA, Brooke M (2001) Boys with

reading disabilities and/or ADHD: distinction in early childhood.

J Learn Disabil 34:98–111

Attention deficit hyperactivity disorder (ADHD)

in obsessive compulsive disorder (OCD) subjects:

prevalence and clinical correlates

Maria Aparecida da Silva1, Ivete Gattas1, Beatriz Shayer1,Samantha Nunes2, Aline Reis2, Tallta Villanova Figueiredo1,Paula Duran1, Ana Paola Robatto Nunes2, Katya Argolo Godinho1,Alice de Mathis3, Ygor Ferrao4, Leonardo Fontenelle5,Maria Conceicao do Rosario6

1Department of Psychiatry, Federal University of Sao Paulo, Sao

Paulo, Brazil; ADHD Research Group (LIGADAH); 2ADHD

Outpatient Clinic, Federal University of Bahia, Salvador, Bahia,

Brazil; ADHD Research Group (LIGADAH); 3Department of

Psychiatry, University of Sao Paulo, Sao Paulo, Brazil; OCD

Brazilian Consortium (CTOC); 4Department of Psychiatry, Federal

University of Rio Grande do Sul, Porto Alegre, Brazil, OCD Brazilian

Consortium (CTOC); 5Department of Psychiatry, Federal University

of Rio de Janeiro, Rio de Janeiro, Brazil; OCD Brazilian Consortium

(CTOC); 6Department of Psychiatry, Federal University of Sao Paulo,

Sao Paulo, Brazil; ADHD Research Group (LIGADAH), OCD

Brazilian Consortium (CTOC)

E-mail for correspondence: [email protected]

Introduction: ADHD affects 6% of children and 4% of adults, with

high comorbidity rates, such as obsessive-compulsive disorder

(OCD), reported in around 30% of childhood OCD. Nevertheless, the

prevalence of OCD in ADHD adults is unclear.

Objective: To evaluate the prevalence and associated clinical char-

acteristics of ADHD in a sample of adult OCD outpatients.

Methods: A cross-sectional study assessing 949 adult OCD outpa-

tients. Subjects were assessed with structured interviews and scales.

Results: All together 16.7% of the sample fulfilled criteria for ADHD.

Compared to OCD patients without ADHD (OCD-ADHD), subjects

with ADHD (OCD + ADHD) presented significantly more severe OC

symptoms in the DYBOCS dimensions: Sexual/religion; symmetry;

hoarding; and miscellaneous. Regarding the YBOCS, the scores for

obsessions and compulsions were significantly more severe in the

OCD + ADHD group. Tics were significantly more frequent in the

OCD + ADHD group.

Discussion: This study demonstrated that there are significant dif-

ferences between the two groups. The data also revealed that only a

small proportion of the ADHD subjects had been treated with

methylphenidate.

Conclusions: This study emphasizes the need for carefully investi-

gation for ADHD symptoms in OCD patients.

References

1. Geller DA, Biederman J, Faraone SV, Cradock K, Hagermoser L,

Zaman N et al (2002) Attention-deficit/hyperactivity disorder in

children and adolescents with obsessive-compulsive disorder:

fact or artifact? J Am Acad Child Adolesc Psychiatry 41:52–55

2. Miguel EC, Ferrao YA, Rosario MC, Mathis MA et al (2008) The

Brazilian Research Consortium on obsessive-compulsive spec-

trum disorders: recruitment, assessment instruments, methods for

the development of multicenter collaborative studies and

preliminary results. Rev Bras Psiquiatr 30(3)

3. Kessler RC, Adler L, Barkley R, Biederman J et al (2006) The

prevalence and correlates of adult ADHD in the United States:

results from the National Comorbidity Survey Replication. Am J

Psychiatry 163:716–723

Ego depletion underlies dysfunction in backward

inhibition paradigm in adults with ADHD

Shirley Dorchin, Nachshon Meiran

Department of Psychology, Ben-Gurion University of the Negev,

Beersheba, Israel

Objective: The backward inhibition (BI) paradigm, used to measure

the ability to inhibit irrelevant task sets from previous trials, was

examined in adults with ADHD. Based on Baumeister’s ego depletion

theory, the authors postulate that ADHD symptoms of disinhibition

reflect a state of ego depletion due to reduced stamina or steeper

deterioration of resources.

Methods: Participants were seven matched pairs of students with and

without ADHD. Accuracy and reaction time (RT) on two consecutive

BI tasks were measured to assess self control during and after a

depleting task.

Results: Both groups showed a similar BI effect in RT on the first and

more complex task. However, a significant group 9 lag-2 interaction

effect was found on the following second task, such that the BI effect

was eliminated for the ADHD subjects.

Conclusions: ADHD and control groups’ performance differed only

in the second BI task, which may indicate that the state of ego

depletion caused by the first task led to ADHD subjects’ inability to

exert inhibition during the successive task.

Subjective and behavioral dimensions of impulsivity

and their relation to a self-report adaptation

of the SWAN in a sample of Spanish adolescents

M. Figueroa-Varela1, S. Rodrıguez-Ruiz1, M.A. Munoz2,M.C. Fernandez Santaella1, J. Vila1, L. Anllo-Vento1,3

1Department of Psychology, University of Granada, Granada, Spain;2Department of Psychology, University of the Balearic Islands, Palma

de Mallorca, Spain; 3F. Oloriz Institute of Neurosciences, University

of Granada, Granada, Spain

Introduction and objective: Despite the prominent role of impul-

sivity as a diagnostic criterion in ADHD and other mental health

conditions, its definition remains elusive, leading to contradictory

findings [1].

Methods: We investigated the potential relationship between a self-

report measure of impulsivity and a measure of behavioral inhibition;

the association of both measures with the modulation of behavioral

responses to the valence of affective pictures; and the connection

between all variables and an adaptation of the SWAN rating scale [2].

Seventy-eight Spanish adolescents (15.98 ± 1.26) were selected


123

according to their total score on the Spanish adaptation of the Plutchik

Impulsivity Scale [3]. They also filled a self-report adaptation of the

SWAN rating scale, and were administered a computerized emotional

Go/No-Go task.

Results: Significant correlations were obtained between subjective

and behavioral impulsivity measures, and between levels of self-

perceived impulsivity and reports of attention problems and skills.

There was no observable modulation of affective responses by level

of impulsivity.

Discussion and conclusions: We conclude that subjective and

behavioral measures of impulsivity are related when impulsivity is

narrowly defined. Adolescents that perceive themselves as impulsive

also tend to assess themselves as less attentionally competent.

References

1. Reynolds B, Ortengren A, Richards JB, de Wit H (2006)

Dimensions of impulsive behavior. Personality and behavioral

measures. Personality Individ Differ 40:305–315

2. Swanson J, Schuck S, Mann M, Carlson C, Hartman K, Sergeant

J, Clevenger W, Wasdell M, McCleary R (2006) Categorical and

dimensional definitions and evaluations of symptoms of ADHD:

the SNAP and SWAN rating scales. University of California,

Irvine

3. Paez F, Jimenez A, Lopez A, Raull Ariza JP, Ortega Soto H,

Nicolini H (1996) Estudio de validez de la traduccion al

castellano de la Escala de Impulsividad de Plutchik. Salud

Mental 19:10–12

The functional pharmacogenetics of carboxylesterase 1,

the enzyme that metabolises methylphenidate

Johnny Graham, A.M. Milne, D.R. Coghill, M.W.H. Coughtrie

University of Dundee, Ninewells Hospital and Medical School,

Dundee DD1 9SY, UK

Introduction and objective: Treatment of ADHD with methylphe-

nidate is complicated by interindividual variation, risking treatment

failure and increased adverse events [1]. In this study, we investigated

the possible role played by interindividual variation of detoxification

of MPH, by examining the functional pharmacogenomics of carb-

oxylesterase 1 (CES1), the most important enzyme in metabolism of

oral MPH [2].

Methods: (1) Cloning, cell line expression and characterisation of

human CES1 wild type and two common gene variants [3] using

spectrophotometry, to examine of the consequences of sequence

variation. (2) Examination of the possible functional consequences of

variation.

Results: In comparison to wild type, the most common candidate

CES1 polymorphism shows around a threefold reduction in expres-

sion level together with around a fourfold reduction of catalytic

activity. There is some evidence for reduced protein stability also.

Discussion: The most common CES1 gene variant, which may be

present in around 15% of some populations, produces reduced

protein levels and reduced enzymatic activity when reproduced in

vitro, and may have implications for individuals in receipt of

methylphenidate displaying this variant, or other drugs metabolised

by CES1.

References

1. Gualtieri CT, Wargin W, Kanoy R, Patrick K, Shen CD,

Youngblood W et al (1982) Clinical studies of methylphenidate

serum levels in children and adults. J Am Acad Child Psychiatry

21(1):19–26

2. Sun Z, Murry DJ, Sanghani SP, Davis WI, Kedishvili NY, Zou Q

et al (2004) Methylphenidate is stereoselectively hydrolyzed by

human carboxylesterase CES1A1. J Pharmacol Exp Ther

310(2):469–476

3. Marsh S, Xiao M, Yu J, Ahluwalia R, Minton M, Freimuth RR

et al Pharmacogenomic assessment of carboxylesterases 1 and 2.

Genomics 84(4):661–668

Evidence-based programmes for parents of children

diagnosed with ADHD: is research translating

into practice in the UK context?

Corinne A. Huntington, Katey C. Weizel, Kirsten A. Asmussen

National Academy for Parenting Research, Institute of Psychiatry,

King’s College London, London, UK

Introduction and objective: Research consistently suggests that

parenting programmes play a vital role in the treatment of ADHD.

This study aims to compare what research evidence suggests as

effective practice against what is currently available to parents.

Methods: A systematic review was conducted to identify parenting

interventions which significantly improve outcomes for children with

ADHD. A second desk-based review was conducted to identify par-

enting support routinely offered to families living within the UK.

Results: This review identified several practices that contribute to

positive benefits for children and parents. These practices include

specific training to improve children’s concentration, as well as their

behaviour. By contrast, the majority of programmes currently avail-

able in the UK offer behaviour-modification training only.

Discussion: This study highlights gaps in current practice and makes

recommendations about how these gaps can be addressed.

Conclusion: A growing body of evidence suggests that children with

ADHD are best supported through parent training that addresses

children’s behavioural issues and inability to concentrate. Current

practice should therefore offer parents a variety of strategies to

address the multiple problems associated with ADHD.

References

1. Fabiano GA, Pelham WE, Coles EK, Gnagy EM, Chronis-

Tuscano A, O’Connor B (2009) A meta-analysis of behavioral

treatments for attention-deficit/hyperactivity disorder. Clin Psy-

chol Rev 29:129–140

2. Jans T, Philipsen A, Graf E, Ihorst G, Gerlach M, Warnke A

(2009) Does the treatment of maternal attention deficit and

hyperactivity disorder (ADHD) enhance the efficacy of a

behavioural parent training for the treatment of their children’s

ADHD? Study protocol of a randomized controlled multicentre

trial. Atten Deficit Hyperact Disord 1:33–34

3. Patterson GR, DeBaryshe BD, Ramsey E (1989) A developmen-

tal perspective on anti-social behavior. Am Psychol 44:329–335

Gene expression correlates of baseline activity level

in mice

Nicholas Ilott1, Lin Liu1, Cathy Fernandes1, Jose Payo-Cano1,Philip Asherson1, Leonard Schalkwyk1

1MRC SGDP Research Centre, Institute of Psychiatry, King’s College

London, De Crespigny Park, London SE5 8AF, UK


123

Introduction: A core symptom of ADHD is overactivity, forming

part of the hyperactive/impulsive component of the disorder. ‘Home-

cage’ or baseline activity level is thought to best represent the over-

activity observed in ADHD.

Methods: We have used microarrays to correlate hippocampal

mRNA profiles of heterogeneous stock (HS) mice with measures of

baseline activity level (AL).

Results: A number of genes were significantly correlated (FDR

q \ 0.1) with baseline AL measures. Further, pathway analysis

revealed the potential involvement of serotonin and circadian rhythm

signalling.

Discussion: Baseline AL in HS mice may represent a behaviour that

is relevant to the study of ADHD, which can be used to investigate the

nature of individual differences in behaviour in the context of indi-

vidual differences in gene expression.

Conclusion: Baseline AL is, at least in part, governed by genetic

variation that gives rise to baseline gene expression changes, with the

potential involvement of differential serotonin and circadian rhythm

function.

Stability of ADHD symptoms across age groups:

an item response theory analysis of 705 clinically-

referred individuals

Christian Kieling, Eduardo Chachamovich, Breno Matte,Claiton H. Bau, Paulo Belmonte-de-Abreu, Eugenio H. Grevet,Luis Augusto Rohde

ADHD Program, Hospital de Clinicas de Porto Alegre, Universidade

Federal do Rio Grande do Sul, Porto Alegre, Brazil

Introduction and objectives: ADHD among adults has been

increasingly recognized over the last years, despite the difficulties of

adapting diagnostic criteria and symptom dimensions to the assess-

ment of these patients. In this study, we compared the performance of

a symptom rating scale (SNAP-IV) across age groups.

Methods: Baseline assessments of 705 individuals (286 children and

adolescents and 419 adults) referred for ADHD treatment in an out-

patient clinic setting were analyzed. Item response theory analyses

were conducted to identify specific item performance across age and

gender groups.

Results: Preliminary results indicate a two-factor solution corrobo-

rating the inattention and hyperactivity/impulsivity dimensions of

ADHD. Three inattention and six hyperactive/impulsive items

showed differential item functioning across age groups. Unidimen-

sional analyses revealed a set of five inattention-related items with

interval psychometric properties across both age groups. In the

hyperactivity/impulsivity domain, however, no single solution was

possible, with two final sets of six and four items demonstrating

interval properties for children/adolescents and adults, respectively.

Discussion: Initial results suggest that items reflecting specific ADHD

symptoms have distinct psychometric properties among children/

adolescents and adults.

References

1. Rohde LA (2008) Is there a need to reformulate attention deficit

hyperactivity disorder criteria in future nosologic classifications?

Child Adolesc Psychiatr Clin N Am 17(2):405–420

2. McGough JJ, Barkley RA (2004) Diagnostic controversies in

adult attention deficit hyperactivity disorder. Am J Psychiatry

161:1948–1956

3. Kieling C, Kieling RR, Rohde LA, Frick PJ, Moffitt T, Nigg JT,

Tannock R, Castellanos FX (2010) The age at onset of attention

deficit hyperactivity disorder. Am J Psychiatry 167(1):14–16

Clinical audit of assessment of psychiatric co-morbidity

in children diagnosed with ADHD in a community

CAMHS team

Shashi Kiran

Easington CAMHS, Tees, Esk and Wear Valleys NHS Foundation

Trust, Durham, UK

Introduction and objective: Psychiatric co-morbidity is frequently

encountered in children who have a diagnosis of ADHD and can

have a significant impact on the course of the illness as well as

on response to interventions. The objective of the current audit

was to evaluate the process of assessment for these co-morbidities

in a community CAMHS team in children with a diagnosis of

ADHD.

Methods: Retrospective case reviews of 65 cases with a diagnosis of

ADHD in the Easington CAMHS team were carried out using an audit

tool was constructed for this purpose.

Results: There was no systematic assessment of psychiatric co-mor-

bidity in most of the children reviewed with ODD was the most

common co-morbidity with ASD, mood and anxiety disorders also

observed. None of these were however as frequently seen as men-

tioned in published literature.

Discussion: Difficulties in carrying out retrospective case reviews,

need for good medical records and the deficits of the electronic sys-

tem used for primary medical records.

Conclusion: There is a need to have protocols that help in assessment

and documentation of psychiatric co-morbidity in ADHD in com-

munity CAMHS teams.

References

1. Jensen PS, Hinshaw SP, Kraemer HC (2001) ADHD comorbidity

findings from the MTA study: comparing comorbid subgroups. J

Am Acad Child Adolesc Psychiatry 40(2):147–158

2. Steinhausen H, Novik T, Baldurrson G et al (2006) Co-existing

psychiatric problems in ADHD in the ADORE cohort. Eur Child

Adolesc Psychiatry 15(Suppl 1):s787–s793

3. Faber A, Kalverdijk LJ, de Jon-van den Berg LT et al (2010) Co-

morbidity and patterns of care in stimulant-treated children with

ADHD in the Netherlands. Eur Child Adolesc Psychiatry

19(2):159–166 [Epub 2009 Nov 6]

Strengths in children with ADHD

Liisa Klenberg

University of Helsinki, Helsinki, Finland

[email protected]

Introduction and objectives: This study describes positive charac-

teristics of children with ADHD combined type (ADHD-C) and

inattentive type (ADHD-I) according to teacher evaluations.

Methods: Teachers were asked to describe strengths of children with

ADHD-C (n = 190) and ADHD-I (n = 25), and a group of typically

developing children (TD, n = 701) aged 7–15 years using 25 items in

the Attention and Executive Functions Rating Inventory (ATTEX,

Klenberg et al., in press).

Results: Overall, TD children had higher ratings of strengths than

children with ADHD. However, children with ADHD-C had higher

ratings than TD children in eight items, and children with ADHD-I

had higher ratings in three items. Summary scores of strengths,

formed on the basis of a factor analysis, showed that the ADHD-C

group had higher ratings in ‘‘Imaginativeness’’.


123

Discussion: Strengths related to ADHD could be interpreted as

positive equivalents of typical symptoms (e.g. quickness, hyperac-

tivity; ability to ponder on things, absentmindedness).

Imaginativeness may be a typical capacity of children with ADHD-C.

Conclusion: Research on strengths may highlight resources that aid

coping of children with ADHD.

Reference

1. Klenberg L, Jamsa S, Hayrinen T, Lahti-Nuuttila P, Korkman M

(2010) The attention and executive function rating inventory

(ATTEX): psychometric properties and clinical utility in diag-

nosing ADHD subtypes. Scand J Psychol (in press)

Why do clinicians choose to start, stop and change

medication? The Decisions Regarding ADHD

Management (DRAMa) study

Hanna Kovshoff1, Sarah Williams1, May Vrijens2, Lucy Yardley1,Marina Danckaerts2, Margaret Thompson1, Edmund Sonuga-Barke1,3

1School of Psychology, University of Southampton, Southampton,

UK; 2Department of Neurosciences, Katholieke Universiteit Leuven,

Leuven, Belgium; 3Department of Experimental Clinical and Health

Psychology, Ghent University, Ghent, Belgium

Introduction and objectives: Clinicians have the difficult task of

weighing up numerous sources and types of information when diag-

nosing and treating children with ADHD. The aim of this poster is to

present the results of a qualitative study exploring the decision

making processes of 60 child psychiatrists and paediatricians from the

South of England and Belgium.

Methods: Sixty participants from two European Countries took part

in semi-structured interviews covering their decision making pro-

cesses through every stage of service provision including assessment,

diagnosis, commencing treatment, and the monitoring, adaptation or

cessation of treatment approaches.

Results: Key themes from the thematic analysis will be presented

along with the implications these have on the decision making

practices of clinicians in the UK and in Belgium.

Discussion: The qualitative interview data will be used to create a

questionnaire that will cover key items relating to medication deci-

sions in ADHD treatment and longer term case management.

Conclusion: Overall, the objective is to improve ADHD-related

clinical practice in the longer term through the development of more

systematic and robust treatment approaches.

This project is funded by Shire Pharmaceuticals.

Reference

1. Kovshoff H, Williams SV, Yardley M, Danckaerts L, Thompson

M, Sonuga-Barke E (2009) The Decisions Regarding ADHD

Management (DRAMa) Study: a cross comparison of factors

influencing clinical practice. In: Proceedings of the 20th EUNE-

THYDIS Meeting, Winchester

Consortium for the Lifespan Examination of ADHD

Registry (CLEAR) Study: a phase 4 international,

longitudinal, observational study of individuals

with attention-deficit/hyperactivity disorder (ADHD)

Robert Lasser1, Meryl Brod2, Srinivas Tetali1, Lisa Politza1,Matthew Dauphin1, Philip Asherson3, Michael Huss4

1Shire Development Inc., Wayne, PA, USA; 2The Brod Group, Mill

Valley, CA, USA; 3MRC Social, Genetic and Developmental

Psychiatry Centre, Institute of Psychiatry, Denmark Hill, London,

UK; 4Child and Adolescent Psychiatry, Johannes Gutenberg-

University Mainz, Mainz, Germany

Introduction: There is a need for a better global understanding of the

course and impact of adult ADHD across the patient lifespan.

Objective: CLEAR will allow for multiple real-world comparisons of

clinical, patient-reported experience of care and cost outcomes in

ADHD.

Methods: CLEAR is a prospective, observational disease registry of

adults with ADHD that will follow approximately 2,500 patients in 5

countries for a minimum of 5 years.

Sample study questions:

What is the course of ADHD?

What is the impact of diagnosis and/or treatment in childhood for

adult ADHD parameters?

What are the short- and long-term treatment patterns, and their

consequences, for ADHD?

What are the differences between ADHD treatments?

What is the relationship between disease severity and compliance?

Does treatment and cost associated with ADHD differ

geographically?

What is the relationship between ADHD status (symptom severity)

and treatment costs?

Conclusion: This presentation will discuss the rationale and design of

CLEAR as well as present the ethical, methodological and logistical

challenges that CLEAR needs to address to be a scientifically rigorous

and successful global adult ADHD registry.


Association of maternal lifestyle factors in pregnancy

and birth weight with attention-deficit/hyperactivity

disorder in a population of Italian children

M. Marino2, M. Polizzi2, E. Sarnataro2, R. Cascella2, R. Maresca1,L. Castaldo1, M.P. Riccio2, A. Pascotto2, C. Bravaccio1

1Department of Pediatrics, University ‘‘Federico II’’, Naples, Italy;2Neuropsychiatry Department ‘‘Second University of Naples’’,

Naples, Italy


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Introduction and objective: Pregnancy- and birth- related risk fac-

tors of ADHD include maternal smoking, alcohol ingestion and

prematurity. We compared the correlation between these risk factors

with a sample of Campanian children with ADHD.

Methods: 194 ADHD subjects (DSM criteria), from 4 to 22 years old,

52.1% with ADHD combined type (ADHD-C). Data were collected

using medical folders of the patients; we estimated the prevalence of

maternal smoking, prenatal exposure to alcohol and low birth weight.

Pearson analysis was made to estimate the association between these

factors and ADHD.

Results: There is a statistically significant correlation between

smoking and use of alcohol during pregnancy and ADHD-C, and, in

our sample, between LBW and these factors (r = 0.330; r = 0.301).

Discussion: There is a correlation between the onset of ADHD and

pregnancy risk factors in our population; found data are similar in

frequency to the data of literature.

Conclusions: Maternal smoking during pregnancy, prematurity,

alcohol exposure, contribute as causes of ADHD. The analysis of a

population of ADHD Campanian children put in evidence a correla-

tion with the previous statements.

References

1. Millichap JG (2008) Etiologic classification of attention-deficit/

hyperactivity disorder. Pediatrics 121:e358–e365

2. Crocker N, Vaurio L, Riley EP, Mattson SN (2009) Comparison

of adaptive behavior in children with heavy prenatal alcohol

exposure or attention deficit/hyperactivity disorder. Alcohol Clin

Exp Res 33(11):2015–2023

3. Markussen Linnet K, Dalsgaad S, Obel C, Wisborg K, Henrikse

TB, Rodriguez A, Kotimaa A, Moilanen I, Thomsen PH, Olsen J,

Jarvelin MR (2003) Maternal lifestyle factors in pregnancy risk

of attention deficit hyperactivity disorder and associated behav-

iors: review of the current evidence. Am J Psychiatry 160:1028–

1040

ADHD and Neanderthals

J.A. Medina1, T.L. Netto1, M. Muszkat2

1Medicine Centre of Physical Activity and Sport (CEMAFE), Federal

University of Sao Paulo (UNIFESP), Sao Paulo, Brazil; 2Child’s

Neuropsychological Attendance Center (NANI), Federal University

of Sao Paulo (UNIFESP), Sao Paulo, Brazil

Introduction: Genes with characteristics of ADHD populations, the

allele gene DRD4-7R, had great proliferation at 40,000 years ago [1],

Europe was shared by nomads’ Neanderthals and Cro-Magnons.

Objective: To describe interactions between Paleolithic environment

and DRD4-7R characteristics.

Methods: It’s an investigation for scientific evidences in scientific

sites.

Results: The presence of gene DRD4-7R in nomads is associated

with better nutritional indices than that observed on assented

condition, this nutritional advantage is linked with mass free of fat

[2]. Humans needed, during his journey to Ardipithecus from

Homo sapiens, to be endurance runners, face the necessity of to

hunt.

Discussion: ADHD individuals show during exercises lower values of

acid lactic, suggesting better performance on endurance sports.

Nutritional aspects associated to the active nomad way of life may

had positive influence, face that aerobic training programs induce

increase in gray matter on cortex cingulate anterior [3], the same brain

area quoted like dysfunctional in ADHD populations.

Conclusion: Active way of life associated to nutritional strategies

may help on development of ADHD children and perhaps, DRD4-7R

could be result of hybridism.

References

1. Wang E, Ding YC, Flodman P et al (2004) The genetic

architecture of selection at the human dopamine receptor D4

(DRD4) gene locus. Am J Hum Genet 74(5):931–934

2. Eisenberg DT, Campbell B, Gray PB et al (2008) Dopamine

receptor genetic polymorphisms and body composition in under-

nourished pastoralists: an exploration of nutrition indices among

nomadic and recently settled Ariaal men of northern Kenya.

BMC Evol Biol 8:173

3. Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash R,

McAuley E, Elavsky S, Marquez DX, Hu L, Kramer AF (2006)

Aerobic exercise training increases brain volume in aging

humans. J Gerontol A Biol Sci Med Sci 61(11):1166–1170

Parent, teacher and self-ratings of ADHD: a twin study

in early adolescence

Andrew Merwood1, Corina U. Greven1, Henrik Larsson2,Philip Asherson1

1MRC Social, Genetic and Developmental Psychiatry Centre,

Institute of Psychiatry, King’s College London, London, UK;2Department of Medical Epidemiology and Biostatistics, Karolinska

Institute, Stockholm, Sweden

Introduction and objective: Research suggests that estimates of

heritability in ADHD differ across informants, specifically that parent

and teacher ratings of ADHD yield higher estimates of heritability

than self ratings. The exploration of such inconsistencies is important,

not least because most genetic and imaging studies of ADHD are

underpinned by the quality of ratings.

Methods: We used a sample of 5,588 12-year-old twin pairs (2,024

MZ pairs, 3,564 DZ pairs) drawn from the UK-representative Twins

Early Development Study (TEDS) to determine the heritability of

parent, teacher and self-ratings on the hyperactivity/inattentiveness

scale of the Strengths and Difficulties Questionnaire (SDQ).

Results: Preliminary analyses based on twin correlations indicate that

self-rated ADHD shows lower heritability (A = 0.48) compared to

parent and teacher-ratings (A = 0.76 and 0.58, respectively). Multi-

variate model fitting is currently in progress.

Discussion: Findings suggest that the heritability of self-rated ADHD

is lower than that of parent-rated ADHD, but also indicate that self-

rated heritability may be more substantial than previously reported for

a young adolescent population.

Conclusion: The heritability of ADHD in adolescence varies as a

function of informants.

DAYAS: a new tool for the assessment of a day profile

of ADHD symptoms

Tanja Wolf Metternich-Kaizman, Dieter Breuer, Manfred Dopfner

Department of Child and Adolescent Psychiatry and Psychotherapy at

the University of Cologne, Robert-Koch-Str. 10, 50931 Cologne,

Germany

Introduction and objective: A new rating scale to assess core

symptoms of ADHD as well as ODD-symptoms and potential side


123

effects of medication across the day in different natural settings has

been developed (DAYAS). The instrument has been tested for reli-

ability and validity and it was used in a medication effectiveness trial

to measure treatment effects.

Methods: 2 studies with DAYAS a short rating scale (6 items). 4

parent ratings + 2 teacher ratings over span of day. (1) 27 outpatients

(mean age = 9.8 years, SD = 1.4; 21 males; 59% medication treat-

ment, diagnosed ADHD) telephone assessments testing validity

(comparison with DSM-IV scales; parent and teacher ratings) and

reliability of DAYAS for daily or weekly evaluation of symptoms.

Additional analysis whether daily assessments could be replaced by

weekly ones. (2) Effectiveness and safety observation of Equasym

XL under routine care conditions. 169 centres in Germany; 810

patients [mean age = 10.3 years; males 81% analysis; t1 pre-treat-

ment; t2; t3 (t1 + 6–12 weeks)]. Further psychometric analysis.

Results: (1) Medium to high correlations of DAYAS with DSM-IV

scales. Satisfying reliability. Daily- can be replaced by weekly ratings

(medium to high correlations). (2) Symptom reduction demonstrated

with DAYAS; high ES in 2nd half of the school day and the early

afternoon. Acceptable reliability.

Discussion/conclusion: DAYAS is feasible, shows satisfying reli-

ability and validity. It seems reasonable that daily can replace weekly

ratings.

Symptoms of attention-deficit hyperactivity disorder

and co-occurring psychiatric symptoms and personality

disorders in young adults: the moderating roles

of gender and parenting

Hsing-Chang Ni1,2, Susan Shur-Fen Gau2,3

1Department of Psychiatry, National Taiwan University Hospital,

Taipei, Taiwan; 2Department of Child Psychiatry, Chang Gung

Memorial Hospital-Linkou Medical Center, Chang Gung University

College of Medicine, Taipei, Taiwan; 3Department of Psychiatry,

College of Medicine, National Taiwan University, Taipei, Taiwan

Introduction and objective: Little is known about the moderating

roles of gender and parenting style in the association between sub-

threshold ADHD and psychiatric comorbid conditions and personality

characteristics in young adults.

Methods: 2,284 incoming college students completed questionnaires

assessing ADHD symptoms (Adult ADHD Self-Report Scale),

DSM-IV psychopathology (Adult Self-Report Scale Inventory-4),

and parenting styles before 16 years old (Parental Bonding

Inventory).

Results: Both ADHD and subthreshold ADHD groups had more

psychiatric comorbidities than the non-ADHD groups (odds ratios

1.7–25.3). Female excess was noted in anxiety and depression and

male excess was noted in OCD, tics, and CD. Increased parental care

but overprotection was associated with decreased symptoms of psy-

chiatric and personality disorders and the likelihood of associations

between ADHD and comorbid conditions.

Discussions: Negative parenting moderated the association between

ADHD and some psychiatric symptoms such as anxiety, depression,

OCD, CD, borderline and antisocial behaviors.

Conclusions: Psychiatric comorbid conditions in individuals with

ADHD symptoms are common. Primary prevention from developing

psychiatric conditions should be implemented by including appro-

priate parenting and in individuals with ADHD and subthreshold

ADHD as well.

References

1. Faraone SV, Kunwar A, Adamson J, Biederman J (2009)

Personality traits among ADHD adults: implications of late-onset

and subthreshold diagnoses. Psychol Med 39:685–693

2. Biederman J, Faraone SV (2004), The Massachusetts General

Hospital studies of gender influences on attention-deficit/

hyperactivity disorder in youth and relatives. Psychiatr Clin

North Am 27:225–232

3. Ellis B, Nigg J (2009) Parenting practices and attention-deficit/

hyperactivity disorder: new findings suggest partial specificity of

effects. J Am Acad Child Adolesc Psychiatry 48:146–154

Developmental risk factors for hyperactive girls

I. Octavio, E. Taylor, S. Young

Institute of Psychiatry, King’s College London, London, UK

Introduction and objective: Hyperactivity was found a risk factor

for developing later behavioural and social problems in boys (Taylor

1996). The developmental course for girls is uncertain. The main

study objective was to clarify the developmental risk related to

hyperactivity in a longitudinal epidemiological study.

Method: Girls between 6 and 7 years recruited from all mainstream

schools in East London were followed up for 8 years. Groups were

defined by Rutter A2 and B2 questionnaire scores and a detailed

interview on parents performed by researchers (Taylor et al. 1991).

Results: Hyperactivity in adolescence was predicted by the initial

level of hyperactivity (b = 0.349, t = 2.920, p \ 0.01). Conduct

problems at age 7 emerged as a significant factor in the stepwise

regression. School problems were predicted by the level of hyperac-

tivity (b = 0.285, t = 2.010, p \ 0.05). Conduct problems at age 7

emerged as a significant factor in the regression analysis.

Discussion: Findings show hyperactivity as a predictor for behav-

ioural and school functioning in girls. Outcomes seem to be worsened

by conduct problems.

Conclusion: The presence of hyperactivity is a risk factor for girls in

adolescence.

References

1. Taylor E et al (1996) Hyperactivity and conduct problems as risk

factors for adolescent development. J Am Acad Child Adolesc

Psychiatry 35(9):1213–1226

2. Taylor E, Sandberg S, Thorley G, Giles S (1991) The epidemi-

ology of childhood hyperactivity. Maudsley. Monograph No. 33.

Oxford University Press

The attribution of hostile intent and assessment

of behavioural response in children with disruptive

behaviour disorder

P. Olgiati1, M. Saccani1, F. Aggio1, C. Lenti1



Introduction and objectives: Numerous studies have examined

Social Information Processing (SIP) in children with aggressive


123

behaviour. The purpose of this study was to investigate the various

steps of SIP in children with attention deficit/hyperactivity disorder

(ADHD) in comorbid with oppositional defiant disorder (ODD) or

conduct disorder (CD).

Methods: The sample included of 34 male children aged 7–13 years,

divided into three groups (healthy children; ADHD + ODD;

ADHD + CD). All the children were given questionnaires to assess

the attribution of others’ intent and of behavioural response.

Results: The ADHD + CD group was significantly more likely to

attribute hostile intent to ambiguous actions than the control group.

As far as the assessment of the behavioural response was confirmed,

the two clinical groups believed that the aggressive response is sig-

nificantly easier to implement and will lead to more satisfactory

results interpersonally than the control group. Only the ADHD + CD

group was more likely to implement this behaviour compared to

healthy children and to the ADHD + ODD group.

Discussion: The ADHD + CD group shows a deficit in several steps

of the SIP, while the ADHD + ODD group shows no alterations in the

early steps of the SIP.

Conclusions: The comorbidity with CD is characterized by greater

impairment of social information processing.

Keywords: ADHD, CD, ODD, SIP, Attribution of intent

Comorbidities in a sample of Brazilian children

with attention deficit hyperactivity disorders (ADHD)

S.M. Palma, S. Rizzutti, L.F.C. Scaramuzza, T.S. Franco, S.A.O. Sa,R. Stuque, D. Dias, K.R. Pradella, D.A.X. Gouvea, D.L.F. Barbosa,R.A.D.S. Fıgaro, O.F.A. Bueno, M. Muszkat

Departamento de Psicobiologia, Universidade Federal de Sao Paulo,

Sao Paulo, SP, Brazil

Sonia Maria Motta Palma: Rua Embau 54, 04039-060 Sao Paulo, SP,

Brazil. E-mail: [email protected]

Objective: The aim of this study was to evaluate clinical aspects

related to ADHD in particular the ones concerning the association

with comorbidities.

Methods: One hundred fifty children, aged from 7 to 14, were

selected. Children who met the inclusive criteria were referred to a

multidisciplinary assessment schedule. The neuropsychological pro-

tocol included: Intellectual Level Assessment (Scale WISC-III

abbreviated), EACI-P Scale, Computerized Attention Test, Rey Fig-

ure, CBCL Scale and screening for delimitation of comorbidities.

Results: 75 children (55 M and 20 F) fulfilled the criteria for ADHD.

Out of the 75 children, 33 cases (44%) had complaints of comor-

bidities, whereas 22 cases (66.6%) presented anxiety disorder, 8

patients (24.2%) had oppositional defiant disorder and 3 cases had

conduct disorder (9%). With regards to mood disorders, it was

observed bipolar disorder in 3 cases (9%) and 3 cases met the criteria

for severe depression (9%).

Conclusion: In our study, the presence of comorbidities was found in

44% of the diagnosed cases. Such finding emphasises the importance

of global assessment. The impact of comorbidities may modify the

therapy, rehabilitation strategies and prognosis.

References

1. Garland AF, Hough RL, Mccabe KM, Yeh M, Wood PA, Aarons

GA (2001) Prevalence of psychiatric disorders in youths across

five sectors of care. J Am Acad Child Adolesc Psychiatry

40:409–418

2. Tramontina S, Schmitz M, Polanczyk G, Rohde LA (2001)

Juvenile bipolar disorder in Brazil: clinical and treatment

findings. Biol Psychiatry 53:1043–1049

3. Tannock R (2009) ADHD with anxiety disorders. In: Brown TE

(ed) ADHD comorbidities: handbook for ADHD complications in

children and adults. American Psychiatric Publishing, Inc., pp

131–155

Stress response in Brazilian children and adolescent

with attention deficit and hyperactivity/impulsivity

disorder

Sonia Maria Motta Palma, Diana Fernandes, Mauro Muskat,Helena Maria Calil



Objective: This study aims at assessing the functioning of the HPA

axis in response to stress through the measure of plasma cortisol in

children with ADHD and in a matched healthy control group.

Method: Samples for measurement of salivary cortisol were collected

from 38 children with clinical diagnosis of ADHD and 38 controls paired

by sex, age and education. The sample collection was done through the

use of salivette�, 15 min before the application of Continuous Perfor-

mance Test (CPT) as an stressor (pre-test); 20 min (post-test I); 40 min

(post-test II); and 60 min (post-test III) after the test application.

Results: There were no differences between ADHD and control group

baseline cortisol levels (p = 0.41). Following the stressor test, the

ADHD group had higher salivary cortisol levels than the group control

at 20 min (p = 0.01), 40 min (p = 0.003) and 60 min (p = 0.03).

Conclusion: The application of CPT has not induced an increase of

cortisol, but rather a decrease. However, the ADHD group had an

increase of cortisol levels following the stressor test, throughout the

observation period (60 min after the test application).

Keywords: Attention-deficit hyperactivity disorder, Inattention,

Children, Adolescent, Stress, Cortisol

Active pharmacovigilance in developmental

neuropsychiatry: the Italian ADHD National Registry

Cristina Peddis1, Eleonora Sanna1, Tatiana Usala1, Romano Arcieri2,Elena Germinario2, Massimilano Bugarini2, Pietro Panei2,A. Zuddas1

1Child Neuropsychiatry, Department of Neuroscience, University of

Cagliari, Cagliari, Italy; 2Department of Therapeutic Research and

Medicines Evaluation, Italian National Institute of Health, Rome, Italy

Introduction: In 2007 the Italian Drug Regulatory Agency activated

the ADHD National Registry. The aims were pharmacovigilance,

prevention of abuse/disuse, assessment of methylphenidate and ato-

moxetine efficacy and side effects.

Patients and methods: Patients aged 6–17 years with ADHD treated

by atomoxetine or MPH were enrolled. Complete clinical assessment

was performed at enrolment and every 6 months; adverse events were

investigated by questionnaires and data collected by centralized

electronic CRF.

Results: 1,452 patients were enrolled. 54% of these were prescribed

with atomoxetine. For 64 patients (53 ATX) clinicians reported severe

adverse events: dysphoria, suicidal ideation, anorexia, seizures, neu-

rogenic bladder, aphasia, lengthened QT, tachycardia, hypotension. 19

patients discontinued medication (18 ATX), 2 changed to MPH.

Discussion: The register was able to verify diagnostic accuracy and

patterns of drug prescription establishing accurate benefit/risk balance


123

and ensuring high level of health protection for the population. ATX

was the most prescribed medication. Reports of adverse reactions and

rate of early withdrawn were significantly higher for this medication

than for MPH.

Conclusion: The register may serve as model for others psychiatric

disorders in children and adolescents.

ADHD, obesity: an Italian clinical sample

M.C. Porfirio1, G. Giana1, A. Benvenuto1, S. Giovinazzo1,R.C. Belvedere1, P. Curatolo1

1Department of Child Psychiatry, Tor Vergata University, Rome,

Italy

Introduction and objective: Recently, a possible association

between obesity and ADHD has been described both in adults and in

children (Lam et al. 2007). Current findings link both conditions to

the dopamine system in body weight, eating, and ADHD, among

others. The present study estimated the prevalence of overweight and

obesity in a sample of children and adolescents with ADHD.

Methods: The group comprised 115 patients (106M, 9F), mean age

12.26 years, with a diagnosis of ADHD, according to DSM-IV TR criteria,

evaluated for their weight status by Body Mass Index (BMI) for age and

gender: All patients were drug free at moment of clinical examination.

Results: 31.3% of subjects shown the presence of any overweight/

obesity, with 20.8% classified with overweight and 10.4% with

obesity. None significantly differences on BMI value were found in

accordance with age.

Conclusions: Clinical studies can be useful for early identification of

ADHD subjects at high risk for overweight/obesity, enabling us to

understand to what extent the symptoms of impulsivity, executive

difficulties, reward deficits are correlated with overweight/obesity and

altered patterns of eating behavior.

References

1. Cortese S, Angriman M, Maffeis C, Isnard P, Konofal E,

Lecendreux M, Purper-Ouakil D, Vincenzi B, Bernardina BD,

Mouren MC (2008) Attention deficit/hyperactivity disorder

(ADHD) and obesity: a systematic review of the literature. Crit

Rev Food Sci Nutr 48(6):524–537

2. Lam LT, Yang L (2007) Overweight/obesity and attention deficit

and hyperactivity disorder tendency among adolescents in China.

Int J Obes 31:584–590

3. Volkow ND, Wang GJ, Kollins SH, Newcorn JH, Telang F,

Fowler JS, Zhu W, Logan J, Ma Y, Pradhan K, Wong C, Swanson

JM (2010) Evaluating dopamine reward pathway in ADHD:

clinical implications. JAMA 302(10):1084–1091

CBCL as a screen tool to distinguish neuropsychological

and behaviour profile in a sample of Brazilian children

with attention deficit hyperactivity disorders (ADHD)

S. Rizzutti, S.M. Palma, L.F.C. Scaramuzza, T.S. Franco, S.A.O. Sa,R. Stuque, D. Dias, K.R. Pradella, D.A.X. Gouvea, D.L.F. Barbosa,R.A.D.S. Fıgaro, O.F.A. Bueno, M. Muszkat



Corresponding author: Fax: +55-11-55498476, Tel: +55-11-55496899;

E-mail address: [email protected] (S. Rizzutti); Rua Embau, 54 Vila

Clementino, Sao Paulo CEP: 04039-060, Brazil

Objective: The aim of this paper was to evaluate if CBCL inventory

would help to identify and correlates to clinical and neuropsycho-

logical profile in children with ADHD.

Methods: The assessment involved 120 children aged 7–14. They

were referred to a multidisciplinary assessment schedule which con-

sisted of medical and neuropsychological evaluation, as well as

social, neurological, psychiatrical examination, family assessment

and Child Behavior Checklist (CBCL).

Results: With regards to the DSM IV criteria for ADHD, 75 children.

There was negative correlation between the digit score and the Corsi

test, especially in reverse order. Children with high scores for

hyperactivity and impulsivity had a low performance for functional

memory. Children with oppositional defiant disorder presented pat-

tern changes in adaptability when there was a change in the rhythm

the stimuli were presented and lower adaptation to time variability

(Hit RT), in addition to higher rates of omission in the CPT.

Conclusion: This study suggests multiple interrelations between the

scores of CBCL measures and neuropsychological battery, which are

useful for a more detailed delimitation of the clinical profile of

children with ADHD in order to select better approaches in a cog-

nitive rehabilitation program.

References

1. Biederman J, Monuteaux MC, Greene RW et al (2001) Long-

term stability of the Child behavior Checklist in a clinical sample

of youth with attention deficit hyperactivity disorder. J Clin Child

Psychol 30:492–502

2. Holtmann M, Goth K, Wockel L, Poustka F, Bolte S (2007)

CBCL-pediatric bipolar disorder phenotype: severe ADHD or

bipolar disorder? J Neural Transm 5(2):155–161

3. Holtmann M, Bolte S, Goth K, Dopfner M, Pluck J, Huss M,

Fegert JM, Lehmkuhl G, Schmeck K, Poustka F (2007)

Prevalence of the Child Behavior Checklist—pediatric bipolar

disorder phenotype in a German general population sample.

Bipolar Disord 9(8):895–900

ADHD as an independent risk factor for illicit drug use

Maria Antonia Serra-Pinheiro1, Evandro Silva Freire Coutinho2,Isabella Souza1, Camilla Pinna1, Didia Fortes1, Catia Araujo3,Claudia Szobot4, Luis Augusto Rohde4, Paulo Mattos1

1Psychiatric Institute of the Federal University of Rio de Janeiro, Rio

de Janeiro, Brazil; 2National School of Public Health, Oswaldo Cruz

Foundation, Rio de Janeiro, Brazil; 3Federal University of Rio de

Janeiro, Rio de Janeiro, Brazil, 4Federal University of Rio Grande do

Sul, Rio Grande do Sul, Brazil

Introduction and objective: ADHD is associated with illicit drug use

(IDU). However, this increased risk of IDU is frequently attributed to

the comorbidity of ADHD with disruptive disorders (DD). The

objective of this study is to investigate if ADHD is associated with

IDU, when controlling for DD.

Methods: A meta-analysis and a meta-regression were performed

based on articles in which the association between ADHD and IDU

was estimated, while controlling for DD.

Results: Fifteen articles presented odds ratios (OR) for people with

ADHD symptoms versus controls, controlling for disruptive symp-

toms. The pooled OR for IDU in those with ADHD symptomatology was

1.35 (0.90–2.03), p = 0.15, with a heterogeneity between studies of 55%.

The power of the meta-analytic study was 30%. Studies controlling for

socioeconomic status were associated with smaller OR.

Conclusion: The existing data does not substantiate an independent

association between ADHD and IDU. However, even the combination


123

of all available studies is still limited in power to find a statistical

significant increase in chance of around 30%. There is a definite need

of additional studies.

References

1. Szobot CM, Rohde LA, Bukstein O, Molina BS, Martins C,

Ruaro P, Pechansky F (2007) Is attention-deficit/hyperactivity

disorder associated with illicit substance use disorders in male

adolescents? A community-based case-control study. Addiction

102(7):1122–1130

2. Fergusson DM, Horwood LJ, Ridder EM (2007) Conduct and

attentional problems in childhood and adolescence and later

substance use, abuse and dependence: results of a 25-year

longitudinal study. Drug Alcohol Depend 88S:S14–S26

3. August GJ, Winters KC, Realmuto GM, Fahnhorst T, Botzet A,

Lee S (2006) Prospective study of adolescent drug use among

community samples of ADHD and non-ADHD participants. J Am


Differential effect of intranasal dopamine on activity,

non-selective and selective spatial attention, tyrosine

hydroxylase and DARPP32 histochemistry in

prepuberal Naples High Excitability Rats.

Lucia A. Ruocco1, Maria A. de Souza Silva3, Davide Viggiano2,Concetta Treno1, Claudia Mattern3, Joseph P. Huston4* and AdolfoG. Sadile1

1Department of Experimental Medicine, Faculty of Medicine,

II University of Naples, Naples, Italy; 2Department of Health

Sciences, University of Molise, Campobasso, Italy; 3M & P Pharma

AG, Stans, Switzerland; 4Center for Behavioral Neuroscience,

University of Dusseldorf, Dusseldorf, Germany

Neuropsychiatric problems such as Autism and Attention Deficit/

Hyperactivity Disorder (ADHD) are characterized by hyperactivity and

attention problems. Intranasal application of dopamine (IN-DA) in adult

normal rats increases motor activity in different behavioural tasks via

DA receptors on mesostriatal and mesolimbic DA neurons (De Souza

Silva et al., 2008). The aim of this study was to investigate the effects of

prepuberal IN-DA on activity, non selective (NSA) and selective spatial

attention (SSA), tyrosine hydroxylase and DARPP-32 histochemistry in

prepuberal male rats of the Naples High Excitability line (NHE). The

latter are a genetic model for the mesocortical variant of ADHD with

altered executive functions (Ruocco L.A. et al., 2009). NHE rats

received daily application of DA (0.0, 0.075, 0.15, 0.3 mg/kg) into both

nostrils, for 15 days from day 28 to day 42. One hour after last IN-DA,

rats were tested in a Lat maze and a radial maze on successive days.

Activity was monitored by frequency of horizontal (HA) and vertical

activity (VA; rearings and leanings against the walls), NSA and SSA by

duration of rearing and leaning episodes in the Lat maze; in the radial

maze SSA was assessed by position of the first repetitive arm entry.

Behavioural data showed 1) a decreased HA with 0.3 mg/kg; 2)

increased VA by rearings with 0.075 mg/kg; 3) increased duration of

leaning with 0.3 mg/kg; 4) increased working memory with 0.15 mg/kg.

Histochemical data revealed 1) an increase TH expression in medial and

lateral mesencephalon and dorsal and ventral striatum with 0.3 mg/kg.

In summary, the differential effect of IN-DA in NHE rats consisted in

reduced hyperactivity (0.3 mg/kg), improved non-selective (0.075 mg/

kg) and selective attention (0.15 mg/kg) and increased density of TH-

positive sites (0.3 mg/kg). While increased TH expression might reveal

the signal nature of DA itself for pruning of DA terminals, the beha-

vioural data suggest a potential application of IN-DA for therapeutic

management of ADHD in children.

*Supported by a MIUR 2005–2007 grant to AGS and by a Young-

Investigator project, coordinated by Walter Adriani as PI, to LAR.

References

1. De Souza Silva MA, Topic B, Huston JP, Mattern C (2008)

Intranasal dopamine application increases dopaminergic activity

in the neostriatum and nucleus accumbens and enhances motor

activity in the open field. Synapse 62:176–184

2. Ruocco LA, Sadile AG, Gironi Carnevale UA (2009) Modeling the

mesocortical variant of ADHD: the Naples high excitability rats.

In: Gordon SM, Mitchell AM (eds) Attention deficit hyperactivity

disorder. Nova Science, New York, pp 85–106

The Freedom from Distractibility Index (FDI) and its

usefulness in the clinical diagnoses of children

and adolescents with ADHD

Beatriz Shayer1, Samantha Nunes2, Aline Reis2,Tallta Villanova Figueiredo1, Paula Duran1,Ana Paola Robatto Nunes2, Katya Argolo Godinho2,Maria Aparecida da Silva1, Ivete Gattas1,Maria Conceicao do Rosario1

1Department of Psychiatry, Federal University of Sao Paulo, Sao

Paulo, Brazil; ADHD Research Group (LIGADAH); 2ADHD

Outpatient Clinic, Federal University of Bahia, Salvador, Bahia,

Brazil; ADHD Research Group (LIGADAH)

E-mail for correspondence: [email protected]

Introduction: ADHD is frequent and heterogeneous. Neuropsycho-

logical tests are valuable in the search for more homogeneous subgroups.

The Freedom from Distractibility Index (FDI) from WISC-III is related to

sustained attention and working memory skills which are affected in

ADHD. However its clinical utility in diagnosing ADHD is questionable.

Objectives: To investigate the relevance of the FDI for a better

characterization of ADHD subgroups.

Method: Subjects were assessed at two outpatient clinics, with the

instruments: Risk and Medical Factor Questionnaire; SNAP-IV; K-

SADS; WISC-III Digit Span, Arithmetic, Vocabulary, Block Design.

Results: Eighty-four subjects, mean age 9.5 years (SD = 2.8) were

assessed. Mean scores were: IQ = 97.9 (SD = 12.8); FDI = 93.2

(SD = 15.2); SNAP-Inattention = 18.8 (SD = 5.2), SNAP-hyperactivity/

impulsivity = 19.2 (SD = 6.6); SNAP-total = 37.9 (SD = 10.2). There

were significant differences between the SNAP scores according to the

KSADS subtypes, with more severe scores for the hyperactive/impulsive

and combined subtypes. There was a significant correlation between total IQ

and FDI scores.

Discussion: FDI did not present associations with symptom severity

nor ADHD subtypes although Hyperactive/impulsive and combined

subtypes presented poorer scores. FDI was not associated with clin-

ical variables and was not useful for diagnosing ADHD.

References

1. Reinecke MA, Beebe DW, Stei MA (1999) The third factor of the

WIS-III: it’s (probably) not freedom from distractibility. J Am


2. Mayes SD, Calhoun SL (2004) Similarities and differences in the

Wechsler Intelligence Scale for Children-Third Edition (WISC-

III) profiles: support for subtest analysis in clinical referrals. Clin

Neuropsychol 18:559–572

3. Coutinho G, Mattos P, Malloy-Diniz LF (2009) Neuropsycho-

logical differences between attention deficit hyperactivity

disorder and control children and adolescents referred for

academic impairment. Rev Bras Psiquiatr 31(2):141–144


123

First clinical and epidemiologic data of adult ADHD

in Hungary: results of the first epidemiologic study

and the initial experiences of the adult ADHD

outpatient service

Viktoria Simon1, Pal Czobor1,2, Istvan Bitter1

1Semmelweis University Budapest, Department of Psychiatry and

Psychotherapy, Budapest, Hungary; 2Nathan Kline Institute for

Psychiatric Research, Orangeburg, New York, USA

Introduction and objectives: Although ADHD in childhood is a well

known and treated condition in Hungary, outpatient services dedicated

for the treatment and diagnosis of adult ADHD are completely missing.

However, according to the first Hungarian data, estimated prevalence of

ADHD among adults was 1.35%, based on DSM-IV diagnostic criteria

[1]. The objective of this poster is to present the initial experiences of the

first Hungarian adult ADHD outpatient service.

Methods: The evaluation process includes detailed psychiatric eval-

uation, assessment of ADHD symptoms and related impairments both

in adulthood, and retrospectively in childhood, as well as neuropsy-

chiatric evaluation and application of the CAARS [2].

Results: In the first 14 months of the outpatient service, out of 44

people evaluated, 37 was diagnosed with ADHD.

Discussion: Basic demographic characteristics, comorbidity and

current therapies, along with our main experiences with administra-

tion and feedbacks are summarized briefly in this presentation.

Conclusions: Our first experiences in the outpatient service, together

with the estimated high prevalence of ADHD among adults predict a

real challenge in the future for adult psychiatrists in Hungary, with

regard to differential diagnosis and treating comorbid states of adult

ADHD.

References

1. Bitter I, Simon V, Balint S, Meszaros A, Czobor P (2009) How do

different diagnostic criteria, age and gender affect the prevalence of

attention deficit hyperactivity disorder in adults? An epidemiolog-

ical study in a Hungarian community sample. Eur Arch Psychiatry

Clin Neurosci (in press). doi:10.1007/s00406-009-0076-3

2. Conners CK, Erhardt D, Sparrow EP (1999) Conners’ Adult

ADHD Rating Scales (CAARS). Multi-Health Systems Inc.

Early differential diagnostic between autism spectrum

disorders and ADHD

Judith Sinzig, Hannah Bell, Dagmar Morsch

Department of Child and Adolescent Psychiatry, University of

Cologne, Cologne, Germany

Introduction and objective: It is well known that almost half of

children with autism spectrum disorder (ASD) suffer from hyperac-

tivity, inattention and impulsivity and almost 75% were primarily

diagnosed with ADHD. The goal of this study was to identify specific

behaviors of children with either ASD or ADHD, in order to differ-

entiate even in pre-school age between the two disorders.

Methods: 159 children aged 4–8 years old with ADHD (n = 37) or

ASD (n = 53) and a typically developing group (TD; n = 69) were

compared. The applied screening-questionnaire comprised 86 items, that

were chosen from well-evaluated questionnaires for ADHD and ASD.

Results: For autism specific items we found significant differences

between the groups ASD and ADHD/TD and for ADHD specific items

significant differences for ASD/ADHD and TD as well. 14 relevant

items of the screening questionnaire could be identified via discrimi-

natory power and item prevalences. The items comprised ToM-deficits,

impairments in communication and interaction as well as hyperactivity.

Discussion and conclusion: Our findings show that the assessed

questionnaire makes a contribution to identify specific behaviors

problems in early childhood, in order to avoid early false diagnosis

and medical maltreatment and to screen ADHD-children with regard

to ASD symptoms.

Adolescent outcome of child attention deficit

hyperactivity disorder in primary care setting. A 7 year

follow-up

Srebnicki Tomasz, Brynska Anita

Medical University of Warsaw, Warsaw, Poland

Introduction and objective: The aim of the research was to test the

functioning of patients with ADHD at young adult follow up in

comparison with control group. All 180 subjects (mean age

17.3 years) received long-term interventions.

Methods: Out of 180 subjects, 101 were included in the research. All

subjects we re-assessed for ADHD. Both groups were asked to complete a

set of questionnaires. The same procedure was applied to control group.

Results: 63% of subjects still met the criteria for ADHD. The reliability of

diagnosis was 88%. ADHD was more prevalent in families with lower SES.

No relationship was found between ODD/CD and the intensity of the

decrease of symptoms of ADHD. The majority of patients received com-

bined interventions. The quality of pharmacological interventions was not

very different from international guidelines. No relationship was found

between the presence of ADHD, subtype and degree of symptoms intensity

at second assessment and functioning. Patients with ADHD reported sig-

nificant impairment in school functioning. The prevalence of ADHD in

parentswassignificantlygreater than in general population.Subject reported

more problems on CBCL and YSR scales related with mood and anxiety

disorders and ADHD. A relationship was found between psychostimulant

mediation and lower intensity of problems on YSR and CBCL scales.

Discussion/conclusion: The results point at significant improvement

of functioning of patients with ADHD. School functioning is most

affected by symptoms of ADHD. The type of pharmacological

interventions is related with functioning of patients with ADHD.

Beyond the usual suspects: histamine and ADHD

D. Turic1, C.M. Cornforth1, M. Thompson1, E.J. Sonuga-Barke1

1Developmental Brain Behaviour Laboratory (DBBL), School of

Psychology, University of Southampton, Southampton, UK

Introduction and aim: Histamine, despite being the neurotransmitter

with versatile roles and having influence on numerous brain functions,

has been rarely examined in the ADHD field. The aim of this research

is to explore whether genes controlling brain histamine are implicated

in ADHD.

Methods: Licensed drugs target the catecholamine system—espe-

cially the dopamine system. While effective in the short term at

reducing symptoms their long-term benefits appear limited. It is

important to develop novel drugs that target alternative brain systems.

Results: Stevenson et al. (2010) have recently produced the first line

of evidence of a link between histamine genes and ADHD. Functional

polymorphisms of HNMT involved in the degradation of histamine


123

http://dx.doi.org/10.1007/s00406-009-0076-3

moderated the effects of exposure to artificial food additives in a large

double blind trial in children.

Discussion: Histamine is involved in a wide range of physiological

functions including learning and memory, and locomotion. The evi-

dence suggests a potential role of histamine in the pathophysiology of

ADHD.

Conclusion: Recently published molecular genetic data combined

with animal studies showing the role of histamine in ADHD-related

cognitive processes, suggest that the histamine system as an inter-

esting target in ADHD.

Reference

1. Stevenson J, Sonuga-Barke EJ, McCann D, Grimshaw K, Parker K,

Rose Zerilli MJ, Holloway JW, Warner JO (2010) Polymorphisms in

a histamine degradation gene and the moderation of the impact of

food additives on ADHD symptoms in children (in press)

Poster Sessions B: Cognitive-EnergeticFactors in ADHD

Does response variability predict distractibility

among adults with attention-deficit/hyperactivity

disorder?

Zachary W. Adams, Walter Roberts, Mark T. Fillmore,Richard Milich

University of Kentucky, Lexington, USA

Introduction and objective: Increased intra-individual variability in

response time (RTSD) has been observed reliably in ADHD. RTSD is

assumed to reflect attentional lapses and distractibility, though evi-

dence for the validity of this connection is lacking. Thus, we assessed

whether RTSD is an indicator of inattention by comparing RTSD on

the stop signal task (SST) to performance on the Delayed Ocular

Return (DOR) Task, a measure of distractibility.

Method: Participants included 30 adults with ADHD and 28 controls.

Participants completed the SST and the DOR task, which measured

subjects’ ability to maintain attention and avoid distraction by

inhibiting reflexive saccades toward distractors.

Results: On the SST, the ADHD group was slower to inhibit than

controls, indicating poorer inhibitory control in ADHD. The ADHD

group also displayed slower RTs, greater RTSD, and more omission

errors. On the DOR task, the ADHD group displayed more premature

saccades (i.e., greater distractibility) than controls. RTSD predicted

frequency of premature saccades on the DOR task but only in ADHD

participants.

Discussion and conclusion: Results suggest that RTSD is uniquely

linked to distractibility among adults with ADHD.

Cortical grey matter in attention deficit hyperactivity

disorder (ADHD): a structural magnetic resonance

imaging (MRI) study

Martin J. Batty, Elizabeth B. Liddle, Alain Pitiot, Roberto Toro,Madeleine J. Groom, Gaia Scerif, Mario Liotti, Tomas Paus,Peter F. Liddle, Chris Hollis

The University of Nottingham, Nottingham, UK

E-mail address: [email protected]

Introduction: Recent years have seen the emergence of a number of

computational techniques to measure brain structure. Here, we used

structural MRI to measure global and regional abnormalities in ADHD.

Methods: T1 weighted MRI brain images were obtained from 49

children (24 Control; 25 ADHD) aged 9-15 years. Tissues were

classified into grey matter (GM), white matter (WM), and cerebro-

spinal fluid (CSF). A further analysis measured cortical thickness for

each lobe, and for 14 regions in the frontal lobe.

Results: Children with ADHD had significantly smaller brains than

controls and lower GM—but not WM—volumes in all lobes. An

analysis of frontal regions showed thinner cortex in the inferior frontal

gyrus (IFG; pars opercularis) bilaterally in children with ADHD.

Discussion: Children with ADHD show both diffuse and regional GM

abnormalities. Consistent with its putative inhibitory function, the pars

opercularis was thinner in the children with ADHD, who, as expected,

had significantly poorer inhibitory performance on a Go/No-go task.

Conclusion: In addition to widespread GM reductions, children with

ADHD show specific reductions in IFG. This finding raises the intriguing

possibility that a developmental abnormality of the pars opercularis may

drive the inhibitory difficulties characteristic of the disorder.

Potentials evoked by transcranial magnetic stimulation

in healthy children and children with ADHD

Stephan Bender1

1University of Frankfurt, Frankfurt, Germany

Introduction and objectives: So far, transcranial magnetic stimula-

tion (TMS) was often limited to the motor (motor evoked potentials)

and visual systems (phosphenes). Now the EEG-response to TMS

allows assessing cortical excitability/inhibition directly [1] and can be

used to investigate inhibition deficits in ADHD.

Methods: We recorded 64-channel EEG while TMS was performed

in children with ADHD and age-matched healthy control children (8–

14 years). The TMS-evoked potential was registered during single

pulses, short term and long term intracortical inhibition as well as

when subjects performed a contingent negative variation (CNV) task.

Results: The TMS-evoked N100 shows a strong age-dependent devel-

opment. It correlates rather with absolute stimulator output than with the

motor threshold. Group differences in inhibition parameters will be

presented, at the moment we are finishing recordings and data analysis.

Discussion: Possible inhibitory deficits in ADHD and how conditioning

TMS stimuli exert their effects in the developing brain will be discussed.

Conclusions: Inhibitory brain functions can be assessed by TMS-

evoked potentials already in children. The TMS-evoked potential

contains important information which cannot be obtained when EMG

responses are assessed.

Reference

1. Bender S (2005) Transcranial magnetic stimulation evokes giant

inhibitory potentials in children. Ann Neurol 58:58–67

Spontaneous low frequency EEG oscillations at rest,

the default-mode network and ADHD

Samantha Broyd1, Suzannah Helps1, Edmund Sonuga-Barke1,2

1Institute for Disorders of Impulse and Attention, Developmental

Brain-Behaviour Laboratory, School of Psychology, University of

Southampton, Southampton, UK; 2Department of Experimental

Clinical and Health Psychology, Ghent University, Ghent, Belgium


123

Introduction: The default-mode interference hypothesis (Sonuga-

Barke and Castellanos 2007) postulates that intrusions from sponta-

neous very low frequency brain activity may be responsible for lapses

in attention in ADHD.

Methods: DC-EEG data was recorded at rest and during an attention

task in three samples, (1) 20 healthy adult controls, (2) 24 non-clinical

adults with high- or low-ADHD scores and (3) a clinic referred

sample of 16 male children with ADHD and 16 healthy age-matched

controls.

Results: In the healthy adult control data set we identified source

differences between the two resting conditions. In the ADHD sam-

ples, we also found that power in the low frequency EEG oscillations

was attenuated from rest to task, and the degree of this attenuation

was lower in ADHD or inattentive participants compared to controls.

Discussion: Inattentive adults and children with ADHD exhibit atypical

spontaneous low frequency resting-state activity. Children with ADHD

may not only show deficits during rest, but may also experience intrusions

of this very low frequency resting-state activity during task performance.

Conclusion: This study provides preliminary support for the default

mode interference hypothesis.

References

1. Helps SK, Broyd SJ, James CJ, Karl A, Chen W, Sonuga-Barke

EJS (2010) Altered spontaneous low frequency brain activity in

attention deficit/hyperactivity disorder. Brain Res 1322:134–143

2. Helps SK, Broyd SJ, James CJ, Karl A, Sonuga-Barke EJS (2010)

The attenuation of very low frequency brain oscillations in

transitions from a rest state to active attention. J Psychophys (in

press)

3. Sonuga-Barke EJS, Castellanos FX (2007) Spontaneous attentional

fluctuations in impaired states and pathological conditions: a

neurobiological hypothesis. Neurosci Biobehav Rev 31:977–986

On- and off-task EEG activity in adults with attention

deficit hyperactivity disorder

Inez Buyck, Roeljan Wiersema

Ghent University, Ghent, Belgium

Introduction and objective: Electroencephalographic (EEG) studies

show enhanced slow wave activity and an elevated theta/beta ratio

during rest in children with ADHD, compared with typically devel-

oping children (Barry et al. 2003). Findings for adults with ADHD are

less consistent (Koehler et al. 2009). In the current study, on- and off-

task EEG activity was evaluated between adults with and without

ADHD.

Methods: EEG was recorded in 13 adults with ADHD and 13 age-

and IQ-matched adults without ADHD during an eyes closed resting

condition and during flanker performance.

Results: During task performance, the anteriorisation of theta activity

observed in controls was absent in adults with ADHD, who in turn

tended to show a less reduced alpha 1 activity. No group differences

in theta/beta ratio were found in either condition.

Discussion: EEG abnormalities in ADHD during rest were not

observed. Our findings suggest abnormalities in slow wave activity in

adults with ADHD during task performance.

Conclusion: Evaluating EEG activity during task performance may

be more useful to discriminate between adults with and without

ADHD.

References

1. Barry RJ, Clarke AR, Johnstone SJ (2003) A review of

electrophysiology in attention-deficit/hyperactivity disorder. I.

Qualitative and quantitative electroencephalography. Clin Neu-

rophysiol 114:171–183

2. Koehler S, Lauer P, Schreppel T, Jacob C, Heine M, Boreatti-

Hummer A, Fallgatter AJ, Herrmann MJ (2009) Increased EEG

power density in alpha and theta bands in adult ADHD patients. J

Neural Transm 116(1):97–104

Disorder-specific brain dysfunctions during vigilance

in children with ADHD and ASD

Kaylita Chantiluke1*, Anastasia Christakou1, Clodagh Murphy2,Anna Smith1, Ana Cubillo1, Declan Murphy2, Katya Rubia1

1Department of Child Psychiatry, King’s College, Institute of

Psychiatry, London, UK; 2Department of Forensic and

Neurodevelopmental Imaging, King’s College, Institute of Psychiatry,

London, UK

*Presenting author

Introduction and objective(s): Children with ADHD and ASD share

deficits in inattention. We used functional magnetic resonance

imaging (fMRI) to investigate disorder-specific brain dysfunctions

during a parametrically modulated vigilance task that increased the

load on sustained attention.

Methods: Age and IQ matched adolescents with ASD (29), ADHD

(28) and healthy controls (24) performed an event-related parametric

Psychomotor Vigilance Task on a 3T MRI scanner with three dif-

ferent temporal delay conditions, increasing vigilance load. Non-

parametric image analysis (XBAM) was used to test for effects of

group, delay and group by delay interaction.

Results: Both disorders were slower in their reaction times to all

delays and showed underactivation compared to controls in left and

right inferior prefrontal cortex, thalamus and basal ganglia, inferior

parietal lobe, SMA and posterior cingulate/precuneus. The only dis-

order-specific effects were reduced activation in left inferior

prefrontal cortex and cerebellar vermis for ADHD (yellow circles).

There was no group by delay effect.

Discussion: The findings may provide neurofunctional underpinnings

for both the observed overlap in attention deficits in both disorders as

well as the enhanced severity of these in ADHD.

Electrophysiological measures of response conflict

and inhibition: a comparison

Lucy Cragg, Madeleine Groom

University of Nottingham, Nottingham, UK

Introduction and objectives: In ADHD research, response inhibition

and conflict paradigms are typically used interchangeably. Moreover,

abnormalities in electrophysiological measures associated with these

paradigms are treated as evidence for dysfunction in a common neural

system. However, this assumption has never been explicitly tested.

Methods: Electroencephalogram data were recorded from 27 healthy

young adults while they completed a version of the flanker paradigm,

adapted from Crone, Jennings and van der Molen (2003), in which

target stimuli could be flanked by stimuli signalling the same

response, a competing response, or no response.

Results: Preliminary analyses show that event-related potentials

(ERPs) for competing response and no response flankers were highly

similar. For both conditions a pronounced negativity was evident at

450 ms compared to same response flankers.


123

Discussion: A similar N450 component is found in the Stroop para-

digm, suggesting that this negativity reflects conflict processing.

Thus, similar conflict processes appear between two competing

responses, or between a response and no response.

Conclusion: Similar neural processes are engaged in both response

conflict and inhibition.

Keywords: Inhibition, Conflict, Flanker paradigm, Electrophysiol-

ogy, ERPs

Reference

1. Crone EA, Jennings JR, van der Molen MW (2003) Sensitivity to

interference and response contingencies in attention-deficit/

hyperactivity disorder. J Child Psychol Psychiatry Allied Discipl

44(2):214–226

Fronto-striatal brain dysfunction in adults

with childhood ADHD and persistent hyperactive/

inattentive behaviours during interference inhibition

and attention allocation

Ana Cubillo1, Rozmin Halari1, Vincent Giampietro2, Eric Taylor1,Katya Rubia1

1Department of Child Psychiatry, King’s College London, London,

UK; 2Department of Biostatistics, Institute of Psychiatry, King’s

College London, London, UK

Introduction/objective(s): Children with ADHD show fronto-striatal

deficits during inhibition and attention allocation. In adult ADHD,

fMRI findings are inconsistent finding either enhanced or decreased

frontal activation and are confounded by medication history and

retrospective diagnoses. In this study we investigate medication-naıve

adults followed up from childhood ADHD.

Methods: fMRI comparison between 11 medication-naıve adults

followed up from childhood ADHD and persistent inattentive/

hyperactive behaviours and 15 age-matched controls during a Simon

task that co-measures attention allocation.

Results: Patients showed reduced activation in left inferior frontal

cortex during both tasks and in addition in striatum during interfer-

ence inhibition. Activation in fronto-striatal regions was furthermore

negatively correlated with symptom severity in patients.

Discussion: The findings show persistence of fronto-striatal dys-

function in medication-naıve adults with ADHD during interference

inhibition and attention allocation.

Keywords: Interference inhibition, Attention allocation, Adult

ADHD, fMRI, Inferior prefrontal cortex

General cognitive functioning as a moderator

of differences in brain anatomy between children

with ADHD and controls

Patrick de Zeeuw1, Hugo G. Schnack2, Rachel M. Brouwer2,Janna van Belle1, Juliette Weusten1, Sarai van Dijk1, Sarah Durston1

1Neuroimaging Lab, Department of Child and Adolescent Psychiatry,

Rudolf Magnus Institute of Neuroscience, University Medical Centre

Utrecht, Utrecht, The Netherlands; 2Structural Neuroimaging Group,

Department of Psychiatry, Rudolf Magnus Institute of Neuroscience,

University Medical Centre Utrecht, Utrecht, The Netherlands

Introduction and objective: Differences in brain anatomy between

children with ADHD and typically developing controls, particularly

in frontostriatal areas, parietal association areas and cingulate are

becoming established neuroanatomical properties of ADHD (Durston

et al. 2009; Valera et al. 2007). The current study investigates the role

of general cognitive functioning on brain anatomy differences in

ADHD.

Methods: Anatomical MRI scans were acquired and processed from

102 control children and 99 children with ADHD. Measures of total

brain, grey and white matter, ventricles and cerebellum were

obtained. Cortical thickness was assessed using MNI Civet. General

cognitive functioning was categorised as below median (TIQ \ 103)

or above median (TIQ C 103).

Results: Results showed a reduction in grey matter volume between

ADHD and controls in the above median IQ category but not in the below

median category. Thickness of the right prefrontal and right temporal

cortices showed a similar pattern of differences between groups.

Discussion: Our results show that brain anatomy changes in ADHD

may vary as a function of cognitive function.

Conclusion: General cognitive functioning may be a moderator of

brain changes in ADHD.

References

1. Durston S, de Zeeuw P, Staal WG (2009) Imaging genetics in

ADHD: a focus on cognitive control. Neurosci Biobehav Rev

33:674–689

2. Valera EM, Faraone SV, Murray KE, Seidman LJ (2007). Meta-

analysis of structural imaging findings in attention-deficit/

hyperactivity disorder. Biol Psychiatry 61:1361–1369

Mapping striatal maturation: a resting state fMRI

study of age-related changes in functional connectivity

Adriana Di Martino1,2, Clare Kelly1, F. Xavier Castellanos1,Michael P. Milham1

1Phyllis Green and Randolph Cowen Institute for Pediatric

Neuroscience, New York, USA; 2Child and Adolescent Psychiatry,


Introduction and objectives: Neuroimaging approaches to the study

of brain development have provided great insight into structural and

functional changes occurring in the cortex. Fewer studies have

focused on age-related changes in subcortical circuitry. Given the

relevance of striatal-cortical circuits for our understanding of ADHD,

and in preparation for future studies in this population, we examined

age-related changes of striatal functional connectivity (FC) in typi-

cally developing children (TDC).

Methods: We examined the FC of six striatal regions in a fMRI

resting state dataset of 20 TDC (7-13 yrs) and compared it to our

previously published adult results.

Results: In TDC, all seeds showed diffuse local FC, with considerable

overlap among seeds. TDC striatal FC thus lacked the regional

specificity observed in adults. The dorsal caudate and ventral striatal

seeds showed FC with paralimbic regions that was absent in adults.

The nucleus accumbens lacked long-distance FC with posterior cin-

gulate that was characteristic of adults.

Discussion and conclusions: Examinations of age-related changes in

striatal-cortical FC permit the identification of vulnerable circuits that can

be targeted in studies of ADHD physiopathology during the life-span.

Keywords: Development, Striatum, Nucleus accumbens, Functional

connectivity, Neuroimaging


123

Structural brain changes in the emotional network

in adult patients with ADHD compared to patients

with major depression and healthy volunteers

Thomas Frodl1,2, Francesco Amico1, Julia Stauber2, Nadine Schaaff2,Nikolaos Koutsouleris2, Maximilian Reiser3, Hans-Jurgen Moller2

1Department of Psychiatry, School of Medicine and Trinity College

Institute of Neuroscience (TCIN), Trinity College, University of

Dublin, Trinity Centre for Health Sciences, Trinity Academic

Medical Centre (The Adelaide and Meath Hospital incorporating the

National Children’s Hospital (AMNCH) and St. James’s Hospital),

Dublin 24, Ireland; 2Department of Psychiatry and Psychotherapy,

Ludwig-Maximilian University, Nussbaumstr. 7, 80336 Munich,

Germany; 3Institute of Radiology, Ludwig-Maximilian University,

Ziemsenstr. 1, 80336 Munich, Germany

Response inhibition, working memory and response

time variability as endophenotypes in attention-deficit/

hyperactivity disorder (ADHD): an event-related

potentials study

Julia Geißler, Marcel Romanos, Klaus-Peter Lesch

Department of Psychiatry, Psychosomatics and Psychotherapy,

University of Wuerzburg, Wurzburg, Germany

Introduction: Recent years saw the concept of endophenotypes

(Doyle et al. 2005) linking genotype and phenotype further our

understanding of complex disorders like ADHD, where candidate

genes of small effect are combined with a heterogeneous phenotype.

Method: Endophenotypes response inhibition, working memory and

response time variability were assessed with CPT, n-back and stan-

dard deviation of reaction times respectively, while a 21 channel EEG

was recorded. NoGo-Anteriorization (NGA) served as marker of

prefrontal functioning (Fallgatter and Strik 1999).

Results: Medication naıve ADHD patients had reduced NGA

(p = 0.052) and increased errors of omission in CPT (p = 0.008) and

1-back (p = 0.049) compared to medicated patients. Midline P2

latencies to target stimuli were greater for controls compared to

medicated patients for both 1-back and 2-back (p = 0.017 and

p = 0.074).

Conclusion: Differences between medication naive and medicated

ADHD patients are the most pronounced. This supports the notion

that stimulant medication not only alleviates behavioural symptoms

but also improves functioning on a neurophysiological level. Retest-

ing and analyses of developmental outcomes are ongoing and results

will be presented shortly.

References

1. Doyle AE, Willcutt EG, Seidman LJ, Biederman J, Chouinard

VA, Silva J, Faraone SV (2005) Attention-deficit/hyperactivity

disorder endophenotypes. Biol Psychiatry 57:1324–1335

2. Fallgatter J, Strick W (1999) The NoGo-Anteriorization as a

neurophysiological standard index for cognitive response control.

Int J Psychophysiol 32(3):233–238

Methylphenidate improves diminished error

and feedback sensitivity in ADHD: an evoked

heart rate analysis

Yvonne Groen1, Lambertus J.M. Mulder2, Albertus A. Wijers2,Ruud B. Minderaa1, Monika Althaus1

1Department of Psychiatry, University Medical Center Groningen,

University of Groningen, Groningen, The Netherlands; 2Department

of Experimental and Work Psychology, University of Groningen,

Groningen, The Netherlands


(ADHD) is a developmental disorder that has previously been related

to a decreased sensitivity to errors and feedback. Supplementary to

the traditional performance measures, this study uses autonomic

measures to further investigate this decreased sensitivity in ADHD

and the modulating effects of medication.

Methods: Children with ADHD, on and off Methylphenidate (Mph),

and typically developing (TD) children performed a selective atten-

tion task with three feedback conditions: reward, punishment and no

feedback. Evoked Heart Rate (EHR) responses were computed for

correct and error trials.

Results: All groups performed more efficiently with performance

feedback than without. EHR analyses showed that enhanced EHR

decelerations on error trials seen in TD children, were absent in the

medication-free ADHD group for all feedback conditions. The Mph-

treated ADHD group showed ‘normalised’ EHR decelerations on

error trials, dependent on the feedback condition.

Discussion/conclusion: Together with previous psychophysiological

studies, the present study suggests a decreased physiological

responsiveness to errors and error feedback in children with ADHD.

To our knowledge, this is the first study showing a normalising effect

of Mph on the EHR responses to aversive events.

References

1. Groen Y, Wijers AA, Mulder LJM, Waggeveld B, Minderaa RB,

Althaus M (2008) Error and feedback processing in children with

ADHD and children with autistic spectrum disorder. Clin

Neurophysiol 119:2476–2493

2. Luman M, Oosterlaan J, Sergeant JA (2005) The impact of

reinforcement contingencies on AD/HD: a review and theoretical

appraisal. Clin Psychol Rev 25:183–213

Error and feedback processing in children with ADHD

and children with autistic spectrum disorder: an EEG

event-related potential study

Yvonne Groen1, Albertus A. Wijers2, Lambertus J.M. Mulder2,Brenda Waggeveld1, Ruud B. Minderaa1, Monika Althaus1

1Department of Psychiatry, University Medical Center Groningen,


of Experimental and Work Psychology, University of Groningen,

Groningen, The Netherlands

Introduction and objective: Substantial overlap exists between the

developmental disorders attention deficit hyperactivity disorder


123

(ADHD) and autistic spectrum disorder (ASD). This study uses

electrocortical measures to compare children with either disorder on

error and feedback processing. Moreover, effects of Methylphenidate

(Mph) on this processing were investigated.

Methods: Subjects performed a feedback-based learning task. Event-

related potentials (ERPs) time-locked to responses and feedback were

derived from the EEG.

Results: Compared to the TD and ASD groups, the medication-free

ADHD group showed: a decreased response-locked Error Related

Negativity (ERN), error Positivity (Pe), and feedback-locked P2a, par-

ticularly as learning progressed throughout the task. The Mph-treated

ADHD group showed normalised learning effects on the Pe and P2a

components. All clinical groups showed (or tended to show) a decreased

feedback-locked late positive potential to negative feedback.

Discussion/conclusion: The ERPs suggest that medication-free chil-

dren with ADHD, but not children with ASD, have a diminished

capacity to monitor their error responses when they are learning by

performance feedback. This capacity partially ‘normalises’ in Mph-

treated children with ADHD. Both children with ADHD and ASD are

suggested being compromised in affective feedback processing.

References

1. Groen Y, Wijers AA, Mulder LJM, Minderaa RB, Althaus M

(2007) Physiological correlates of learning by performance

feedback in children: a study of EEG event related potentials

and evoked heart rate. Biol Psychol 76:174–187

2. Jonkman LM, Van Melis JJM, Kemner C, Markus CR (2007)

Methylphenidate improves deficient error evaluation in children

with ADHD: an event-related brain potential study. Biol Psychol

76:217–229

Atypical pre- and post-stimulus single-trial EEG power

in children with attention deficit/hyperactivity disorder

(AD/HD)

Madeleine J. Groom1, Elizabeth B. Liddle1, Peter F. Liddle1,Gaia Scerif2, Martin J. Batty1, John D. Cahill1,Katherine L. Roberts3, Mario Liotti4, Chris Hollis1

1Division of Psychiatry, University of Nottingham, Nottingham, UK;2Department of Experimental Psychology, University of Oxford,

Oxford, UK; 3School of Psychology, University of Birmingham,

Birmingham, UK; 4Department of Psychology, Simon Fraser

University, Burnaby, Canada

Introduction: Electrophysiological research in ADHD has tradition-

ally focussed on event-related potentials to identify the

neurophysiological basis of deficits in response inhibition and atten-

tion. Alternative measures that retain information about trial-to-trial

fluctuations in brain states and behaviour are likely to be informative.

Methods: Children (9–15 years) with combined-type ADHD

(n = 26) and matched controls (n = 28) performed a Go/No-Go task.

Points awarded/deducted for performance were manipulated across

three motivational conditions. Mean spectral power pre- and post-

stimulus and relationships between power and performance (go RT,

no-go errors) were calculated.

Results: Preliminary analysis indicates that mean pre-stimulus theta

power is significantly greater in ADHD than controls and correlates

negatively with age. Alpha power differs between groups and moti-

vational conditions. There are subtle differences in the relationships

between single trial power and performance between groups.

Discussion: When performing a task requiring attention and inhibi-

tory control, children with ADHD show atypical electrophysiological

responses during an inhibitory control task.

Conclusion: Single trial oscillatory measures reveal atypical neural

processes in children with ADHD which may be relevant to core

deficits in impulsivity, inattention and motivational state.

Keywords: ADHD, Electrophysiology, Oscillations, Inhibitory con-

trol, Attention

24-h heart rate patterns in children with ADHD:

a naturalistic approach

L. Imeraj1, I. Antrop1,2, D. Deboutte1,3, H. Roeyers4

1Ghent University, Department of Psychiatry and Medical

Psychology, Ghent, Belgium; 2University Hospital Ghent, Child and

Adolescent Psychiatry, Ghent, Belgium; 3Antwerp University,

Collaborate Antwerp Psychiatry Research, Antwerp, Belgium; 4Ghent

University, Department of Experimental-Clinical and Health

Psychology, Ghent, Belgium

Introduction and objective: Fluctuations in ADHD symptoms are

theoretically explained by variations in arousal, a factor influenced by

circadian rhythms. This study investigates whether 24-h patterns of

heart rate (HR), an arousal-related marker, support differential circa-

dian processes in children with ADHD. Mediating effects of physical

activity, chronotypology and sleep-wake problems are explored.

Methods: 30 children with ADHD and 30 sex-matched normal class-

mates, aged 6–12, were examined in their naturalistic setting during 5 days:

HR and activity (24/24 h), chronotypology and sleep–wake problems.

Results: Both activity and HR analyses showed significant group

differences, with higher levels in the ADHD group, and significant

day–night differences. Only for activity an interaction effect was

detected, with no group differences during night but marked differ-

ences in the afternoon. Subjective evaluation revealed a later time-of-

day preference in the ADHD group.

Discussion: Raised HR in ADHD during night could not be explained

by nighttime activity levels as these were only higher during day.

Daytime HR levels did not follow daytime activity peaks in ADHD.

Conclusion: Results revealed differential autonomic functioning in

children with ADHD compared to controls.

Effects of methylphenidate on cognitive subprocesses

of probabilistic reversal learning in adult patients

with ADHD: a fMRI study

V. Jucksch1, H. Salbach-Andrae1, A. Beck2, M. Jacker1,F. Schlagenhauf2, U. Lehmkuhl1, M. Huss3, A. Strohle2

1Department of Child and Adolescent Psychiatry, Charite-

Universitatsmedizin Berlin, Berlin, Germany; 2Department of

Psychiatry and Psychotherapy, Charite-Universitatsmedizin Berlin,

Berlin, Germany; 3Department of Child and Adolescent Psychiatry,

Universitatsmedizin Mainz, Mainz, Germany

Introduction and objective: Reward-motivation deficits in ADHD

are correlated with dysfunctions of the brain dopamine reward path-

way (Volkow et al. 2009). Higher dopamine synthesis capacity in the

striatum of healthy adults was associated with better reward-based

learning; MPH decreased BOLD signal in the ventral striatum (VS)

during response switching after negative feedback and modulated

activity in PFC (Bush et al. 2008). Understanding of neural mecha-

nisms by which MPH improves ADHD symptoms is lacking.

Therefore we examine the neural basis of symptom improvement

after MPH treatment.


123

Methods: FMRI was used to measure BOLD responses in 10 adults

with ADHD and 10 controls (CG) performing the Probabilistic

Reversal Learning Task (Cools et al. 2002). Participants underwent

two sessions, while patients were unmedicated or received MPH.

Analysis was conducted via SPM8b.

Results: Medicated patients showed higher activation during correct

behaviour change in anterior cingulate and VS (k = 5; p \ 0.001

uncorr.) as unmedicated patients. Results comparing data of patients

with CG will be presented.

Discussion and conclusion: Results suggest MPH to influence cog-

nitive subprocesses during probabilistic reversal learning. Results

comparing activation patterns of CG and ADHD will give a detailed

picture of reversal learning in patients with ADHD.

References

1. Bush G, Spencer TJ, Holmes J, Shin LM, Valera EM, Seidman LJ et al

(2008) Functional magnetic resonance imaging of methylphenidate

and placebo in attention-deficit/hyperactivity disorder during the

multi-source interference task. Arch Gen Psychiatry 65(1):102–114

2. Cools R, Frank MJ, Gibbs SE, Miyakawa A, Jagust W,

D’Esposito M (2009) Striatal dopamine predicts outcome-specific

reversal learning and its sensitivity to dopaminergic drug

administration. J Neurosci 29(5):1538–1543

3. Volkow ND, Wang GJ, Kollins SH, Wigal TL, Newcorn JH,

Telang F et al (2009) Evaluating dopamine reward pathway in

ADHD: clinical implications. JAMA 302(10):1084–1091

Event rate susceptibility in ADHD: behavioral

and neuroimaging data

Libbe Kooistra1, Jaap J. van der Meere2, Susan Crawford1,Bradley G. Goodyear3,4

1Department of Pediatrics, Behavioural Research Unit, University of

Calgary, Calgary, Canada; 2Department of Clinical Neuropsychology,

University of Groningen, Groningen, The Netherlands; 3Seaman

Family MR Research Centre, Calgary, Canada; 4Department of

Radiology and Clinical Neurosciences, University of Calgary,

Calgary, Canada

Introduction and objective: The study’s objective was twofold: seek

behavioral (study 1) and neuroimaging (study 2) evidence for the

claim that ADHD is associated with a deficiency in activation/effort

allocation systems.

Method 1: A slow (7 s) and fast (1.5 s) event rate Go/NoGo task in

47 children with ADHD (31 ADHD-C; 16 ADHD-PI; 9.3 years) and

39 controls (9.1 years).

Method 2: A slow (7 s) and fast (1.5 s) event rate Go/NoGo task in

10 young adults with ADHD (21.5 years) and 10 controls

(22.3 years), administered in a 3-T scanner.

Results 1: Children’s Go/NoGo performance was event rate depen-

dent, with the ADHD-C group being affected in the slow and the

ADHD-PI group in the fast condition.

Results 2: Accurate inhibition in the ADHD group in the slow con-

dition was associated with widespread fronto-striatal activation,

including the thalamus. For correct Go trials only the ADHD group

showed substantial under-activation in the slow condition.

Conclusions: The abnormal RT and brain activation data in the slowcondition underline a presumed activation regulation deficit in ADHD.

References

1. Dibbets P, Evers L, Hurks P, Marchetta N, Jolles J (2009)

Differences in feedback-and inhibition-related neural activity in

ADHD. Brain Cogn 70(1):73–83

2. Sergeant JA (2005) Modeling attention-deficit/hyperactivity

disorder: a critical appraisal of the cognitive-energetic model.

Biol Psychiatry 57(11):1248–1255

3. van der Meere JJ (2005) State regulation and ADHD. In Gozal D,

Molfese D (eds) Attention deficit hyperactivity disorder: from

genes to patients. Humana Press, New York, pp 413–433

ADHD and EEG-neurofeedback: a double-blind

randomized placebo-neurofeedback controlled

treatment study

M.M. Lansbergen1, M. van Dongen-Boomsma1,2,D. Slaats-Willemse1,2, J.K. Buitelaar2,3

1Radboud University Nijmegen Medical Centre, Donders Institute for

Brain, Cognition and Behaviour, Department of Psychiatry,

Nijmegen, The Netherlands; 2Karakter University Centre for Child

and Adolescent Psychiatry, Nijmegen, The Netherlands; 3Radboud

University Nijmegen, Donders Institute for Brain, Cognition and

Behaviour, Nijmegen, The Netherlands

Introduction and objective: Electroencephalography (EEG)-neuro-

feedback training may be a promising treatment for ADHD [1]. The

present double-blind, randomized, placebo controlled study examines

the effects of EEG neurofeedback in a scientific rigorously way,

because few studies corrected for unspecific therapeutic factors so far.

Methods: 15 children with ADHD (8–15 years) were randomly allocated

to 30 sessions of personalized EEG-neurofeedback or 30 sessions of sham

neurofeedback. Prior to and after 6, 10, 20, and 30 sessions of neurofeed-

back, ADHD symptoms were evaluated and side-effects were monitored.

Results: Eight children were assigned to group A and 6 children to

group B (since it is a double-blind study, results will be presented

without group identification). Preliminary analyses revealed a sig-

nificant improvement of DSM-IV symptoms of inattention and

hyperactivity/impulsivity over time, similar for both groups. No sig-

nificant side effects were reported.

Discussion: Preliminary results indicate that EEG-neurofeedback does

not outperform sham neurofeedback treatment in improvement of clini-

cal symptoms in ADHD children. However, sample size is small so far.

Conclusion: Although preliminary, these results are not promising

regarding the efficacy of EEG-neurofeedback in children with ADHD.

Reference

1. Heinrich H, Gevensleben H, Strehl U (2007) Annotation:

neurofeedback—train your brain to train behaviour. J Child

Psychol Psychiatry 48:3–16

Resting state EEG in children and adults with ADHD

compared to controls

M. Liechti1,2, R. Drechsler1, L. Valko1, M. Dohnert1, S. Maurizio1,H.-C. Steinhausen1, D. Brandeis1,3,4

1Department of Child and Adolescent Psychiatry, University of

Zurich, Zurich, Switzerland; 2Department of Neuropsychology,

Institute for Psychology, University of Zurich, Zurich, Switzerland;3Department of Child and Adolescent Psychiatry and Psychotherapy,

Central Institute of Mental Health, Mannheim, Germany; 4Center for

Integrative Human Physiology, University of Zurich, Zurich,

Switzerland

E-mail: [email protected]


123

Introduction and objectives: Recent work suggests that resting

Electroencephalogram (EEG) theta and theta/beta ratios at Cz are

consistently elevated in attention deficit hyperactivity disorder

(ADHD), applicable as diagnostic markers. We attempted a replica-

tion in a typical child psychiatric EEG research setting and explored

the topography of these presumed markers of ADHD.

Methods: Resting EEG from subjects with ADHD and healthy controls

was recorded for 3 min each with eyes closed and eyes open in children

(8–16 years) and adults (32–49 years). Standard FFT of the 48-channel

EEG (500 Hz/1,024 dp epochs) using average reference followed inde-

pendent component analysis-based eye-artefact correction and

semiautomatic artefact rejection. EEG was tested for increased theta, and

theta/beta ratios in ADHD. Group differences were explored with t-maps.

Results: No consistent theta and theta/beta increases were found in

ADHD (at p \ 0.05 uncorrected). Instead, some measures even ten-

ded to be reduced (e.g. relative theta).

Discussion and conclusions: Our failure to replicate consistent

resting EEG abnormalities in ADHD casts doubt upon neurometric

approaches towards EEG-based ADHD classification. These results

demonstrate that ‘‘classical’’ quantitative EEG markers cannot be

used for ADHD diagnostics in typical child psychiatry settings.

Keywords: Attention deficit hyperactivity disorder (ADHD) classi-

fication, Resting electroencephalogram (EEG), Quantitative EEG,

Frequency bands, Theta/beta

Supported by the SNF project ‘‘MFAA’’ (32-109591).

Divided spatial attention in ADHD: Behavioral

and ERP findings

Vladimir Lopez, Rodrigo Ortega, Francisco Aboitiz

Pontificia Universidad Catolica de Chile, Santiago, Chile

Introduction: It has been reported that ADHD can perform even

better than controls in divided attention tasks.

Methods: We designed a cued spatial attention task in which subjects

are asked to perform a visual search restricted to one or two (out of

four) cued locations. These effects were assessed through behavioral

and EEG/ERP measures in an ADHD and a control matched group.

Results: Reaction times were significantly longer and the performance

poorer for ADHD in all conditions, including divided attention. The

visual P1 and N1 were larger in controls than in ADHD. There was a clear

effect of valid versus invalid cues in both groups although it was larger in

controls. This effect was not present in the control group in the divided

attention condition but it was preserved in the ADHD group.

Discussion/conclusion: Behavioral and electrophysiological data

suggests that ADHD implies a differential strategy of spatial selection

when attention is divided.

Fondecyt 1080219-1090610.

A bifactor model of attention-deficit/hyperactivity

disorder (ADHD): external validation and examination

of developmental change

Michelle M. Martel1, Joel T. Nigg2

1Psychology Department, University of New Orleans, New Orleans,

USA; 2Psychiatry Department, Oregon Health and Sciences

University, Portland, USA

Objective: The current project evaluates whether a bifactor model of

ADHD can account for neuropsychological and temperamental het-

erogeneity and developmental change.

Methods: 548 children (321 boys; 302 with ADHD), 6–18 years, and

406 adults (220 men; 173 with ADHD), 18–37 years old completed a

multi-stage diagnostic assessment. Mothers completed the Early

Adolescent Temperament Questionnaire and California Q-Sort.

Children completed the Stop and Trail-Making Tasks.

Results: Correlations between latent ADHD factor scores and traits/

cognitive control indicated specific inattention was associated with low

extraversion (r = -0.24), high agreeableness (r = 0.14), and high

reactive control (r = 0.18; all p \ 0.01); specific hyperactivity-impul-

sivity was associated with high extraversion (r = 0.29), low

agreeableness (r = -0.46), and low reactive control (r = -0.54).

Latent profile analysis (BIC = 1,709.59) indicated children high in

specific inattention exhibited slower performance; children high in spe-

cific hyperactivity and general ADHD exhibited more set-shifting errors,

worse response inhibition, and more variable response times (F[16,

1,716] = 4.56; all p \ 0.01). Two-group modeling in children and adults

indicated significant differences in factor loadings (v2[133] = 758.82,

p \ 0.01; CFI = 0.97; RMSEA = 0.075).

Conclusion: A bifactor model of ADHD explains heterogeneity and

suggests developmental change in the importance of specific symp-

toms, but not the overall structure.

Event-related brain dynamics in ADHD

Grainne McLoughlin1, Fruhling Rijskdijk1, Jonna Kuntsi1,Philip Asherson1, Nima Bigdely Shamlo2, Jason Palmer2,Scott Makeig2

1MRC SGDP Centre, Institute of Psychiatry, King’s College, London,

UK; 2Institute for Neural Computation, University of California San

Diego, San Diego, USA

Introduction and objective: Independent component analysis (ICA)

(Delorme and Makeig 2004) exploits the temporal resolution of EEG

to provide a richer characterisation of macroscopic neural differences

associated with ADHD. In this study, we investigate the inter-trial

variability in EEG indices of ADHD.

Methods: 68 twin pairs were recruited from the Twins Early

Development Study (TEDS). EEG data was recorded during the fast

task (Andreou et al. 2007). Using ICA, neural event-related activity

was identified in both conditions of the fast task.

Results: We observed that activities of the component processes

varied with time and conditions in several frequency bands.

Discussion: The use of ICA can reveal the dynamics of brain source

activation and synchronization phenomena in ADHD not revealed by

standard scalp data averaging methods. The increased variability of

these parameters in ADHD suggests that there is not an attentional

deficit, per se, in ADHD but an inability to maintain consistent per-

formance over time.

Conclusion: These findings will aid in the characterisation of intra-

individual variability in ADHD, both at the level of cortical pro-

cessing and at the level of behavior.

References

1. Andreou P, Chen W, Christiansen H, Gabriels I, Heise A, Meidad

S, Muller UC, Uebel H, Banaschewski T, Manor I, Neale B,

Oades R, Roeyers H, Rothenberger A, Sham P, Steinhausen H-C,

Asherson P, Kuntsi J (2007). Reaction time performance in

ADHD: improvement under fast-incentive condition and familial

effects. Psychol Med 37:1703–1716

2. Delorme A, Makeig S (2004) EEGLAB: an open source toolbox

for analysis of single-trial EEG dynamics including independent

component analysis. J Neurosci Methods 134(1):9. http://sccn.

ucsd.edu/eeglab

3. Kuntsi J, McLoughlin G, Asherson P (2006) Attention deficit

hyperactivity disorder. Neuromol Med 8:461–484


123

http://sccn.ucsd.edu/eeglab

http://sccn.ucsd.edu/eeglab

fMRI investigation of sustained attention

and sensorimotor synchronization in children

and adults with autistic spectrum disorder.

C.M. Murphy1, A. Christakou2, E. Daly1, P. Johnston1,V. Giampietro3, A. Smith2, D. Spain1, D.G.M. Murphy1*, K. Rubia2

1King’s College London, Institute of Psychiatry, Department of

Forensic and Neurodevelopmental Sciences, London, UK; 2King’s

College London, Institute of Psychiatry, Department of Child

Psychiatry, London, UK; 3King’s College London, Institute of

Psychiatry, Department of Biostatistics, London, UK; * and the M.R.C.

A.I.M.S Network; 4King’s College London, Institute of Psychiatry,

London; University of Oxford; University of Cambridge, UK

Introduction and objective: People with autistic spectrum disorder

(ASD) have deficits in sustained attention [1] and sensorimotor syn-

chronization [2]. We investigated brain function in individuals with

ASD and healthy controls on a sustained attention/vigilance and

sensorimotor synchronization task.

Methods: 46 males (11–35 years) with ASD and 44 age/IQ matched

healthy controls performed an event-related parametric Psychomotor

Vigilance Task that required a motor response to different temporal delays

(3 T MRI scanner): (1) long/unpredictable (2, 5, 8 s) (sustained attention)

and (2) short/predictable delays (500 ms) (sensorimotor synchronization).

Data were analysed using non-parametric FMRI analyses (XBAM) [3].

Results: Individuals with ASD had:

1. slower and variable reaction times to all delays, but there was no

group by delay effect.

2. reduced activation during sustained attention in bilateral inferior/

dorsolateral prefrontal, parietal, striato-thalamic and cerebellar

regions and during sensorimotor synchronisation in cingulate,

parietal, occipital and caudate areas.

Discussion: Individuals with ASD showed reduced recruitment of task-

relevant fronto-parieto-striato-cerebellar and cingulo-striatal networks

during sustained attention and sensorimotor synchronisation, respectively.

Conclusion: The neurofunctional deficits may underlie difficulties of

individuals with ASD with both sustained attention and sensorimotor

synchronization.

References

1. Corbett BA, Constantine LJ (2006) Autism and attention deficit

hyperactivity disorder: assessing attention and response control

with the integrated visual and auditory continuous performance

test. Child Neuropsychol 12(4–5):335–348

2. Jansiewicz EM et al (2006) Motor signs distinguish children with

high functioning autism and Asperger’s syndrome from controls.

J Autism Dev Disord 36(5):613–621

3. Brammer M et al (1997). Generic brain activation mapping in

fMRI. Magn Reson Imaging 15:763–770

Role of feedback in decision making of adolescents

with ADHD

Yehuda Pollak1,2, Varda Gross-Tsur1, Rachel Shoham2, Orit Rabi2,Naama Kroyzer1,2

1Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem,

Israel; 2Department of Psychology, the Hebrew University of

Jerusalem, Jerusalem, Israel

Introduction and objective: Among adolescents with ADHD risk

taking is common, suggesting compromised decision making (DM)

under uncertainty. Using a modified version of the Cambridge

Gambling Task (MCGT), we have recently demonstrated that com-

pared to controls, adolescents with ADHD chose the unlikely

outcome more frequently. The present study aimed to explore the role

of feedback processing in the nature of this peculiar DM.

Methods and results: In the first experiment, adolescents with

ADHD and a control group underwent the MCGT either with or

without serial immediate feedback. Under the feedback condition,

subjects with ADHD tend to choose the unlikely outcome more fre-

quently. However, when feedback was not provided no differences in

DM were observed. On a second experiment, subjects had to choose

between pairs of monetary gambles and no feedback was provided. It

was demonstrated again that ADHD was associated with similar

levels of risk preference and aversion to ambiguity.

Discussion and conclusions: These findings suggest that the unusual

tendency of adolescents with ADHD to choose the unlikely outcome

is limited to DM tasks where feedback is provided.

Structural alteration of substantia nigra in ADHD

Romanos Marcel1, Weise David2, Schecklmann Martin1,Warnke Andreas1, Gerlach Manfred1, Classen Joseph2,Mehler-Wex Claudia3

1University Hospital of Wurzburg, Department of Child and

Adolescent Psychiatry, Wurzburg, Germany; 2University Hospital of

Leipzig, Department of Neurology, Leipzig, Germany; 3University

Hospital of Ulm, Department of Child and Adolescent Psychiatry/

Psychotherapy, Ulm, Germany

Introduction and objectives: Increased echogenicity of the substantia

nigra (SN) is considered as a structural vulnerability marker of the

nigrostriatal dopaminergic system. Alterations of SN echogenicity have

previously been found in Parkinson’s disease and restless-legs-syndrome.

Methods: SN echogenicity was measured in a blinded design bilaterally

by transcranial sonography in 22 children with attention-deficit/hyper-

activity disorder (ADHD) and 22 healthy controls matched for age and sex.

Results: The area of echogenic SN was significantly larger in ADHD

patients compared to healthy controls (p = 0.004; effect size 0.92).

No effects of age, sex or side were found.

Discussion: For the first time increased SN echogenicity is reported in

children with ADHD. Explanations for this finding include a delay of

a developmental SN echogenicity decrease possibly related to dis-

turbance of iron metabolism.

Conclusion: Our results support the notion of a disturbed striatal

dopaminergic system in ADHD and indicate that SN hyperechoge-

nicity might be a general trait marker for dopaminergic vulnerability.

Reference

1. Romanos M, Weise D, Schliesser M, Schecklmann M, Loffler J,

Warnke A, Gerlach M, Classen J, Mehler-Wex C (2010)

Structural abnormality of substantia nigra in attention-deficit/

hyperactivity disorder. J Psychiatry Neurosci 35:55–58

‘‘Jumping to conclusions’’: a new paradigm

for decision-making bias in ADHD

M.D. Salcedo-Marın1, M.L. Barrigon-Estevez2, J.L. Rubio-Gomez1,J.M. Granados-Moreno1, M. Ruiz-Veguilla1, M.S. Centeno-Collado1,A.B. Ramırez-Gonzalez1, M. Ferrin1,2

1Neuropsychiatry Research Unit (NPD), Jaen, Spain; 2Institute of

Psychiatry, London, UK

Corresponding author: [email protected]


123

Introduction: Iowa gambling task have been used in ADHD to study

problems associated with real-life decision making [1, 2].

Method: The aim is to explore this cognitive bias in a sample of 118

children and adolescents with ADHD (DSM-IV) criteria (n = 86

combined; n = 32 inattentive) using a new paradigm (‘‘jumping to

conclusion’’). This task consists of drawings of common objects dis-

played on a computer screen in decreasing degrees of fragmentation.

Results: Five parameters were calculated: Jumping-To-Conclusions

at first stage (JTC-1), Plausibility Rating at first stage (PR-1), Draws-

To-Decision (DTD), Time-Response at first stage (TR-1) and Time-

Response for Draw to Decision (TR-DTD). In comparison with the

inattentive type, significantly more of the combined type patients

made a definitive decision at the first stage (JTC-1: 44.2 vs. 15.6%,

p = 0.004), showed higher levels of conviction when making a

decision (higher Plausibility Rating PR-1), and needed fewer stages

(lower DTD) when making a decision than the inattentive subgroup

(4.54 ± 2.22 vs. 5.62 ± 1.84; p = 0.016).

Conclusions: ADHD combined children make quicker decisions with

a higher level of conviction and may manifest a data-gathering bias

when compared to the inattentive subtype.

References

1. Garon N, Moore C, Waschbusch DA (2006) Decision making in

children with ADHD only, ADHD-anxious/depressed, and con-

trol children using a child version of the Iowa Gambling Task. J

Atten Disord 9(4):607–619

2. Geurts HM, van der Oord S, Crone EA (2006) Hot and cool

aspects of cognitive control in children with ADHD: decision-

making and inhibition. J Abnorm Child Psychol 34(6):813–824

Self-reports, parent-reports and neuropsychological

measures: are they interchangeable when measuring

effortful control?

Vicky Samyn1, Herbert Roeyers1, Patricia Bijttebier2

1Ghent University, Ghent, Belgium; 2University of Louvain, Louvain,

Belgium

Introduction and objectives: Different studies use different mea-

sures to tap EC but it remains unclear whether all these measures are

interchangeable. In the present study we included self- and parent-

reports as well as neuropsychological measures. The main objective

of this study was to investigate the interrelationship between all

measures.

Methods: Participants. 27 children with ADHD and 27 TD controls

(10–15 years). Instruments. EC was measured by means of the ECS,

the ACS and the EATQ-R. The Attention Network Test, a Stroop task

and a go/no-go task were included to assess executive attention,

interference control and inhibitory control, respectively.

Results:

(1) Children with ADHD scored lower than TD children on all

scales. Based on neuropsychological measures, the two groups

could only be differentiated by means of the go/no go task.

(2) All questionnaires were positively interrelated. We found no

relationship between EC total scales and neuropsychological

measures.

Conclusions: Findings suggest that reports on EC are useful when

differentiating between children with ADHD and TD children.

Overall, questionnaires and neuropsychological measures may be

complementary, rather than interchangeable when measuring (aspects

of) EC.

On the stability of instability: psychometric

characteristics of intra-subject variability of reaction

times

Chris Saville1, David Daley1, James Intriligator1, Christoph Klein1,2

1School of Psychology, Bangor University, Bangor, UK; 2University

Hospital for Child and Adolescent Psychiatry, University of Freiburg,

Freiburg, Germany

Introduction and objective: Intra-subject variability of reaction

times (ISV) is a putative endophenotype for several disorders

including attention-deficit hyperactivity disorder (ADHD). Despite

interest in the topic, proper assessment of the psychometric charac-

teristics of ISV is lacking. The present study assesses test–retest

reliability and redundancy of various indices of ISV.

Methods: Sixty-five healthy participants completed a battery of tasks

on two occasions 1 week apart. Test–retest reliability coefficients

were computed for several metrics of ISV.

Results: The data suggest that it is possible to obtain reliable mea-

surements of ISV using certain metrics, including standard deviations,

mean absolute residuals and tau. Reliability was however also shown

to be dependent on number of trials. Many measures were also largely

statistically redundant with regard to one another.

Discussion: Reliably calculating higher moments of reaction time

distributions requires more trials than are needed for measures of

central tendency, a fact that is underappreciated in ISV research and a

possible pitfall for clinical research.

Conclusion: Researchers should consider reliability when measuring

ISV, using sufficient trials and stable measures.

Keywords: Reaction time variability, Reliability, Psychometrics,

Endophenotypes, Ex-Gaussian

Lost in the average: overcoming ERP latency jitter

in populations with highly variable reaction times

Chris Saville1, David Daley1, James Intriligator1, Stephan Boehm1,Christoph Klein1,2

1School of Psychology, Bangor University, Bangor, UK; 2University

Hospital for Child and Adolescent Psychiatry, University of Freiburg,

Freiburg, Germany

Introduction and objective: Research suggests increased intra-

subject variability of reaction times (ISV) is a common feature of

attention-deficit hyperactivity disorder (ADHD). Increased ISV is asso-

ciated with reduced P3 amplitude in event-related potentials (ERPs);

however, as the P3 is partially response-locked, latency jitter represents a

serious confounding variable when comparing groups differing on ISV.

We present data assessing the contribution of latency jitter to P3 reduction

associated with high ISV.

Methods: High and low ISV participants performed an ERP oddball

task. To assess the contribution of latency jitter to P3 reduction, data

were analysed using stimulus-locking, response-locking, a quartile-

based approach, and single-trial analysis.

Results: Averaged ERPs showed reduced P3 amplitude in high ISV

participants. Quartile-wise and single-trial analyses, however, sug-

gested greater variability in the ERPs of high ISV participants.

Discussion: Increased behavioural variability in high ISV participants

is paralleled by increased variability in their ERPs, a characteristic

lost in averaged ERPs.

Conclusion: When investigating populations exhibiting increased

ISV, signal-processing approaches that are not confounded by latency

jitter should be considered.


123

Keywords: Reaction time variability, ERP, P3, Latency jitter, Single-

trial analysis

Deficit in interval timing may be a candidate

endophenotype for attention-deficit hyperactivity

disorder

Susan Shur-Fen Gau1,2, Shoou-Lian Hwang3,4

1Department of Psychiatry, National Taiwan University Hospital,

Taipei, Taiwan; 2Department of Psychiatry, College of Medicine,

National Taiwan University, Taipei, Taiwan; 3Department of

Psychology, National Chengchi University, Taipei Taiwan;4Department of Applied Psychology, Hsuan Chuang University,

Hsinchu, Taiwan

Introduction and objective: Limited attention capacity may be the

underlying mechanism for deficit in interval timing in ADHD. We

tested whether attention capacity related to the time reproduction and

temporal processing without motor processing can be an endophe-

notypes of ADHD.

Methods: We assessed 223 patients with ADHD, 112 unaffected

siblings, and 84 unaffected controls (ages 8–17) by using the time

estimation task and the time reproduction tasks (single and dual tasks)

at 5-, 12-, and 17-s intervals. Gender, age, IQ and comorbidities were

controlled in data analysis.

Results: Patients with ADHD were less precise in all tasks except for

5 s in the time reproduction single task. Unaffected siblings per-

formed at the intermediate between the other two groups in the time

reproduction dual tasks and time estimation tasks. Increased group

difference was associated with increased time intervals.

Discussions: Although unaffected siblings only showed subtle

impairment on dual tasks, their performance was at the intermediate

position in other tasks.

Conclusion: Findings suggest that inadequate attention capacity

measured by the time reproduction paradigm with dual tasks may be

an endophenotype of ADHD.

References

1. Rommelse NN et al (2007) Time reproduction in children with

ADHD and their nonaffected siblings. J Am Acad Child Adolesc


2. Hwang SL, Gau SS, Hsu WY, Wu YY (2010) Deficits in interval

timing measured by the dual-task paradigm among children and

adolescents with attention-deficit/hyperactivity disorder. J Child


Does a shortage of working memory capacity cause

attentional control problems in adolescents

with attention-deficit/hyperactivity disorder:

an ERP study

M. Spronk1, L.M. Jonkman1

1Section of Developmental Cognitive Neuroscience, Faculty of

Psychology and Neuroscience, Maastricht University, Maastricht,

The Netherlands

Introduction and objective: Several studies have indicated that a

lack of attentional control to successfully ignore distracting stimuli

(often seen in ADHD) might be related to a shortage in working

memory capacity (WMC) (Vogel et al. 2005; Burgess et al. 2010).

Since the development of attentional control functions mediated by

the frontal lobe shows continued maturation into adolescence, this

study compares effects of manipulation of WM-load and distraction

(within one paradigm) on behavior and brain measures in adolescents

with and without ADHD.

Methods: Adolescents with ADHD and controls perform a visuo-

spatial WM task manipulating WM-load and presence of distractors.

Effects on RT and accuracy will be studied as well as effects on

specific event-related potential measures that are thought to reflect

neural correlates of maintenance of information in WM (Vogel et al.

2005).

Results/conclusions: We expect to find worse behavioral perfor-

mance and enhanced ERP amplitudes representing maintenance of

more items in memory. Furthermore, distracting stimuli are expected

to affect measures at the behavioral and ERP level to a larger extent in

adolescents with ADHD compared to healthy adolescents, especially

in situations requiring high WMC.

References

1. Vogel EK, McCollough AW, Machizawa MG (2005) Neural

measures reveal individual differences in controlling access to

working memory. Nature 438(7067):500–503

2. Burgess GC, Depue BE, Ruziz L, Willcutt EG, Du YP, Banich

MT (2010) Attentional control activation relates to working

memory in attention-deficit/hyperactivity disorder. Biol Psychi-

atry 67(7):632–640

The bifactor model as a working framework

for understanding the symptom presentation of ADHD

Maggie E. Toplak, Ashley Pitch, David B. Flora, Linda Iwenofu,Karen Ghelani, Umesh Jain, Rosemary Tannock

Department of Psychology, York University, Toronto, Canada

Corresponding author: Maggie Toplak; e-mail: [email protected]

The conceptualization of the symptom structure in ADHD has

implications for research and clinical conceptualizations of ADHD.

The most recent conceptualization in factor analytic studies has

separated inattention from hyperactivity and impulsivity. Our group

examined the bifactor model as a framework for examining the

factor analytic structure of ADHD (Toplak, Pitch, Flora, Iwenofu,

Ghelani, Jain, and Tannock 2009). The bifactor model involves

considering a general factor first, that includes the commonality

among all symptoms, followed by specific factors that include the

remaining variance after the general factor has been taken into

account. We tested correlated and bifactor models in a sample of 201

adolescents referred for ADHD. A bifactor model with two specific

factors best accounted for adolescent ADHD symptoms, according

to both parent and adolescent interview data, and also in parent and

teacher questionnaire data. The idea of a general factor is consistent

with models that acknowledge the integral associations between

inattention, hyperactivity, and impulsivity. This is also consistent

with theoretical models that recognize the multiple pathways that

interact synergistically to give rise to the phenotypic presentation of

ADHD.


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Development of connectivity in the cognitive control

network

Janna van Belle, Tamar van Raalten, Martijn Mulder, Sarah Durston

NICHE Lab, Department of Child and Adolescent Psychiatry, Rudolf

Magnus Institute of Neuroscience, University Medical Centre

Utrecht, Utrecht, The Netherlands

Development of brain activity associated with cognitive control is

characterized by a shift from diffuse to more focal activity (Durston

et al. 2006). The development of the default mode network (DMN)

appears to follow a similar pattern (Fair et al. 2008). In this study

we aimed to map the development of both networks using functional

MR scanning in the same individuals during a cognitive control task

and during rest. Rest and cognitive control regions were used to find

brain areas where activity correlated with these seed regions. Pre-

liminary analyses show that developmental changes in connectivity

of the cognitive control network are characterized by increased

connectivity during cognitive control, paralleled by decreases during

rest. Developmental changes in connectivity of the default mode

show a similar pattern with increased connectivity during rest. The

Default Mode Hypothesis (Sonuga-Barke and Castellanos 2007)

suggests that performance deficits on cognitive control tasks in

ADHD are related to insufficient suppression of the DMN. Indeed,

impaired performance on such tasks has been linked to failure to

suppress activity in the DMN in children with ADHD (Weissman

et al. 2006). Understanding the development of this network and its

relation to development of the cognitive control network is therefore

important for our understanding of ADHD as a developmental

disorder.

References

1. Durston S, Davidson MC, Tottenham N, Galvan A, Spicer J,

Fossella JA, Casey BJ (2006) A shift from diffuse to focal

cortical activity with development. Dev Sci 9(1):1–8

2. Fair DA, Cohen AL, Dosenbach NU, Church JA, Miezin FM,

Barch DM, Raichle ME, Petersen SE, Schlaggar BL (2008) The

maturing architecture of the brain’s default network. Proc Natl

Acad Sci USA 105(10):4028–4032

3. Sonuga-Barke EJS, Castellanos FX (2007) Spontaneous atten-

tional fluctuations in impaired states and pathological conditions:

a neurobiological hypothesis. Neurosci Biobehav Rev

4. Weissman DH et al (2006) The neural bases of momentary lapses

in attention. Nat Neurosci 9(7):971–978

The effect of feedback and dimensional shifts

on set-shifting performance in ADHD and autism

Catharina S. van Meel1,2, Hilde M. Geurts3, Marjolein Luman4

1Institute for Psychological Research, Leiden University, Leiden, The

Netherlands; 2Institute for Psychology, Erasmus University

Rotterdam, Rotterdam, The Netherlands; 3Department of

Psychonomics, University of Amsterdam, Amsterdam, The

Netherlands; 4Department of Clinical Neuropsychology, VU

University Amsterdam, Amsterdam, The Netherlands

Introduction and objective: Research on set-shifting in ADHD

suggests impaired cognitive flexibility. However, it remains unclear

which underlying processes account for this deficit and whether it is

specific to ADHD, or also occurs in other disorders, such as autism-

spectrum disorders (ASD).

Methods: Boys with ADHD and ASD and typically developing boys

(TD) performed a two-dimensional set-shifting task in which they

used visual performance feedback to correctly apply one of two

possible sorting principles.

Results: Although children with ADHD and ASD performed more

poorly than TD children, they effectively used the feedback to figure

out the correct rule. However, while the TD group responded more

accurately when the perceptual dimension of the prior sorting rule

was repeated (intra-dimensional shifts) as opposed to changed (extra-

dimensional shifts), both clinical groups failed to benefit from such

repetitions.

Discussion and conclusion: The high error rates typically observed

during set-shifting may partly arise from a diminished sensitivity to

the task context instead of poor set-shifting or feedback utilization.

Disturbed modulation of working memory representations in pre-

frontal cortex by the midbrain dopamine system may underlie this

deficit.

Keywords: Autism-spectrum disorder, Cognitive flexibility, Intra-

dimensional/extradimensional set-shifting, Task switching, Feedback

learning

References

1. Monsell S (2003) Task switching. Trends Cogn Sci 7:134–140

2. Sergeant JA, Geurts H, Oosterlaan J (2002) How specific is a

deficit of executive functioning for attention-deficit/hyperactivity

disorder? Behav Brain Res 130:3–28

3. Geurts HM, Corbett B, Solomon M (2009) The paradox of

cognitive flexibility in autism. Trends Cogn Sci 13:74–82

ERP correlates and time-frequency analyses of error

monitoring in adults with ADHD

Roeljan Wiersema

Ghent University, Ghent, Belgium

Introduction and objective: Event-related potential (ERP) studies on

error monitoring in adults with ADHD are scarce. In the current

study, error monitoring in adults with ADHD was evaluated by means

of performance measures, ERPs, and wavelet analyses.

Methods: A flanker task was used. Performance measures (including

adaptation measures), error-related ERPs (ERN, Pe), and wavelets,

were compared between adults with and without ADHD.

Results: Overall, adults with ADHD responded slower and more

variably than controls. No difference in congruency effect or post-

error slowing was found. ERP analyses revealed a smaller Pe and

normal ERN in adults with ADHD. Delta band electro-encephalo-

gram (EEG) activity was found to underlie the Pe.

Discussion: Our findings of a smaller Pe in adults with ADHD,

replicates earlier findings (Wiersema et al. 2009), indicating persist-

ing impairment in error awareness. Wavelet analyses supported the

hypothesis that the Pe may reflect a P3-like wave related to errors.

Conclusion: Error awareness is impaired in adults with ADHD and is

related to decreased delta activity in EEG.

Reference

1. Wiersema JR, van der Meere JJ, Roeyers H (2009) ERP

correlates of error monitoring in adult ADHD. J Neural Transm

116:371–379


123

Poster Sessions C: Endophenotypes andGenetic Factors

Methylphenidate administration to adolescent rats

determines enduring plastic changes on striatal gene

expression, and neuronal morphology

W. Adriani1, D. Leo2, U. di Porzio2, G. Laviola1,C. Perrone-Capano2,3

1Istituto Superiore di Sanita, Rome, Italy; 2IGB ‘‘A: Buzzati

Traverso’’, CNR, Naples, Italy; 3Universita degli Studi di Napoli

‘‘Federico II’’, Naples, Italy

Introduction: Methylphenidate (MPH) interacts with brain reward

pathways where it could cause molecular and structural modifications.

It is known that adolescent MPH exposure modulates self-control

behaviour in rats.

Methods: After a 2-week MPH treatment on adolescent rats, we

analyzed striatal transcripts by a genome-wide approach. Then, RT-

PCR and immuno-histochemical experiments were performed to

validate the results. In vitro experiments probed the morphological

alteration following Htr7 stimulation in cultured neurons.

Results: More than 700 striatal genes were up-regulated after MPH

treatment during rat adolescence. RT-PCR validation confirmed more

than 50 genes, encoding for: Post-synaptic Density Proteins, Tran-

scription Factors, Trophic Factors, Extra-Cellular Matrix Proteins,

Synaptic-Vescicle Release Proteins and Neuro-transmitter Receptors.

The 5-hydroxy-tryptamine receptor 7 (Htr7) was strongly and per-

sistently increased in adult MPH-treated rats, together with alterations

of synaptic number and morphology. In vitro, treatment of striatal

neurons with a Htr7 agonist induced ERK phosphorylation and sig-

nificantly increased neurite length, compared to untreated cultures, an

effects blocked by a Htr7 antagonist.

Conclusions: MPH exposure during adolescence produces enduring

plastic changes of reward-related forebrain circuits via the activation

of Htr7.

Keywords: Genome-wide expression profiling, Htr7, Impulsive

behaviour

Dopamine D4 receptor gene: protective and risk alleles

for ADHD in Brazilian population

G.C. Akutagava-Martins1, G. Ferraz1, J.P. Genro1,A.P.M. Guimaraes1, G. Polanczyk2, C. Zeni2, M. Schmitz2,R. Chazan2, L.A.P. Rohde2, M.H. Hutz1, T. Roman1

1Department of Genetics, Federal University of Rio Grande do Sul,

Porto Alegre, Brazil; 2Attention-Deficit/Hyperactivity Disorder

Program (ProDAH), Federal University of Rio Grande do Sul, Porto

Alegre, Brazil

Dopamine D4 receptor gene (DRD4) is considered an ADHD suscepti-

bility gene, being the 7R allele of exon 3 VNTR the putative risk allele.

Here we investigated a possible association between this gene and

ADHD in Brazilian population. 478 DSM-IV ADHD children and/or

adolescents were genotyped for the VNTR, 120 bp tandem duplication,

rs747302 and rs1800955 polymorphisms. Association hypothesis for

isolated polymorphisms and haplotypes was verified through family-

based and dimensional approaches. Associations were observed only for

the VNTR. Using Transmit, undertransmission of 2R (P = 0.031) and

overtransmission of 4R (P = 0.017) alleles were detected in combined

subtype patients. The overtransmission of 4R allele was also seen in

patients with comorbid CD/ODD (P = 0.036). FBAT analyses sup-

ported the 2R finding (P = 0.032). According to the literature, our results

are plausible, especially due to the marked complexity of DRD4 genetic

structure, its high variability among populations and the lack of agree-

ment regarding functional significance of the VNTR. DRD4 complexity

allied to ADHD heterogeneity might be responsible for divergent results.

Its association with ADHD needs further research considering structure

and function of this locus and different ADHD phenotypes.

The dopamine receptor D4 7-repeat allele influences

neurocognitive functioning, but this effect is moderated

by age and ADHD status. An exploratory study

Marieke E. Altink1,3, Nanda N.J. Rommelse4,Dorine I.E. Slaats-Willemse3, Alejandro Arias Vasquez1,2,Barbara Franke1,2, Cathelijne J.M. Buschgens1, Ellen A. Fliers1,Stephen V. Faraone5, Joseph A. Sergeant4, Jaap Oosterlaan4,Jan K. Buitelaar1

1Department of Psychiatry, Radboud University Nijmegen Medical

Center, Donders Institute for Brain, Cognition and Behavior, HP 966,

P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; 2Department of

Human Genetics, Radboud University Nijmegen Medical Centre, HP

855, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; 3Karakter

Child and Adolescent University Centre Nijmegen, Reinier Postlaan

12, 6525 GC Nijmegen, The Netherlands; 4Department of Clinical

Neuropsychology, VU University Amsterdam, Van der

Boechorststraat 1, 1081 BT Amsterdam, The Netherlands;5Departments of Psychiatry and Neuroscience and Physiology, SUNY

Upstate Medical University, Weiskotten Hall 3285, Syracuse, NY

13210, USA

Introduction and objective: This study investigated the functional

consequences of the 7-repeat allele of DRD4 on neurocognitive

endophenotypes of ADHD in the Dutch subsample of the Interna-

tional Multicenter ADHD Genetics study.

Methods: Participants were 350 children (5–11.5 years) and adoles-

cents (11.6–19 years) with ADHD and their 195 unaffected siblings.

An overall measure of neuropsychological functioning was derived

from five neurocognitive and five motor tasks.

Results: The results might indicate that the effect of the DRD4 7-

repeat allele on neuropsychological functioning is dependent on age

and ADHD status. In addition, the 7-repeat allele of DRD4 was

related to a significantly worse performance on verbal working

memory in unaffected siblings, independent of age.

Discussion: Differences in the weight of genetic influences over age on

neurocognitive performance might explain why DRD4 effects are restric-

ted to adolescents in our study. DRD4 may serve as a modifying gene,

acting against a background of other genetic and environmental etiological

factors, rather than as a gene merely increasing the risk for ADHD.

Conclusion: This exploratory study provides new insights into the

functional consequences of the DRD4 7-repeat allele for neuropsy-

chological endophenotypes of ADHD.

References

1. Boonstra AM, Kooij JJ, Buitelaar JK, Oosterlaan J, Sergeant JA,

Heister JG, Franke B (2008) An exploratory study of the

relationship between four candidate genes and neurocognitive

performance in adult ADHD. Am J Med Genet Part B Neuro-

psychiatr Genet 147:397–402

2. Polderman TJ, Posthuma D, De Sonneville LM, Stins JF,

Verhulst FC, Boomsma DI (2007) Genetic analyses of the

stability of executive functioning during childhood. Biol Psychol

76:11–20


123

3. Thompson JL, Pogue-Geile MF, Grace AA (2004) Developmen-

tal pathology, dopamine, and stress: a model for the age of onset

of schizophrenia symptoms. Schizophrenia Bull 30:875–900

Influence of functional dopaminergic polymorphisms

(DAT1 and COMT) on short term memory traces

Stephan Bender1, Tobias Banaschewski2, Franz Resch3,Manfred Laucht4

1University of Frankfurt, Germany, Frankfurt, Germany; 2Central

Institute of Mental Health, Mannheim, Germany; 3University of

Heidelberg, Heidelberg, Germany; 4Central Institute of Mental

Health, Mannheim, Germany

Introduction and objective: Dopaminergic neurotransmission and

working memory are key components in ADHD. We examined the

genetic influences of polymorphisms related to dopamine inactivation

[1] on visual and motor modality-dependent post-processing, i.e. short

term memory encoding.

Methods: From a community-based sample, 64-channel EEG-record-

ings in a continuous performance task (A-X-version) was obtained for

197 healthy subjects and 48 subjects with an ADHD lifetime diagnosis.

Slow negative waves (N700) over the occipito-temporal and contralat-

eral primary motor areas [2, 3] served as target parameters.

Results: Polymorphisms related to dopamine inactivation (10R-6R

DAT1 haplotype, COMT Val158Met polymorphism) influenced the

N700 amplitude in the visual as well as the motor modality. The post-

processing interval was specifically affected. In ADHD subjects,

N700 amplitude was increased and the genetic effects on N700

amplitude were reduced.

Discussion: The reduced effects of the examined functional poly-

morphisms in ADHD subjects may result from a ceiling effect. In

ADHD subjects, dopaminergic neurotransmission may be altered

either by influences from DAT or COMT or other ADHD risk genes.

Conclusion: Motor and visual N700 are endophenotypes which allow

the genomic imaging of the effects of dopamine inactivation during

short term memory encoding.

References

1. Bertolino A (2006) Additive effects of genetic variation in

dopamine regulating genes on working memory cortical activity

in human brain. J Neurosci 26(5):3918–3922

2. Bender S (2008) The topography of the scalp-recorded visual

N700. Clin Neurophysiol 119:587–604

3. Bender S (2006) Cortical motor areas are activated early in a

characteristic sequence during post-movement processing. Neu-

roImage 32:333–351

Gene–environment interactions and attention deficit

hyperactivity disorder: study of small for gestational

age (SGA) children

C.M. Cornforth1,6, D. Turic1,6, J.M.D. Thompson2,6, A.R. Morgan3,4,6,K.E. Waldie5,6, L. Ferguson3,4,6, E.J.S. Sonuga-Barke1,5,6,E.A. Mitchell2,6

1Institute for Disorders of Impulse and Attention, School of

Psychology, The University of Southampton, Southampton, UK; 2The

Department of Paediatrics, The University of Auckland, Auckland,

New Zealand; 3The Department of Nutrition, The University of

Auckland, Auckland, New Zealand; 4Nutrigenomics New Zealand,

Auckland, New Zealand; 5The Department of Psychology, The

University of Auckland, Auckland, New Zealand; 6The Department

of Experimental Clinical and Health Psychology, Ghent University,

Ghent, Belgium

Introduction: SGA is a marker of prenatal adversity and has been

associated with disorders such as ADHD. It has been established that

ADHD is caused by genetic and environmental factors such as

smoking and alcohol consumption during pregnancy.

Aim: To explore gene–environment interactions on ADHD symptoms

in a large sample of SGA children.

Methods: The study is based on data collected by the Auckland

Birthweight Collaborative study. All study children were born at full

term with half of the sample being SGA: the remainder were appropriate

for gestational age (AGA). Extensive data were collected at birth, 1, 3.5,

7 and 11 years. ADHD symptoms were measured using the Conners

Rating Scale and the Strengths and Difficulties Questionnaire.

Results: The results of this study include the independent and com-

bined effects of prenatal environmental adversity and genetic risk

(including the investigation of SNPs for DRD4, DAT1, COMT and

MAO) on ADHD phenotypes.

Discussion: The findings presented suggest that genetic factors

moderate the effects of SGA and that this moderating effect is further

impacted by other environmental risk factors such as maternal stress

and maternal smoking during pregnancy.

A genome-wide association study of motor coordination

problems in children with ADHD identifies genes

involved in brain and muscle function

Ellen A. Fliers1,2*�, Alejandro Arias Vasquez3�, Geert Poelmans1�,Nanda Rommelse1,4, Marieke Altink1,4, Cathelijne Buschgens1,Philip Asherson5, Tobias Banaschewski6, Richard Ebstein7,Ana Miranda8, Robert D. Oades9, Herbert Roeyers10, AribertRothenberger11, Joseph Sergeant12, Edmund Sonuga-Barke5,13,14,Hans Christoph Steinhausen15,16,17, Stephen V. Faraone18,19,Jan K. Buitelaar20, Barbara Franke1,3


Behavior, Radboud University Nijmegen Medical Center, Nijmegen,

The Netherlands; 2Lucertis Child and Youth Psychiatry,

ParnassiaBavo Group, Rotterdam, The Netherlands; 3Department of

Human Genetics, Radboud University Nijmegen Medical Center,

Nijmegen, The Netherlands; 4Karakter Child Psychiatry, Radboud

University Nijmegen Medical Center, Nijmegen, The Netherlands;5Social, Genetic, and Developmental Psychiatry Centre, Institute of

Psychiatry, King’s College London, London, UK; 6Department of

Child and Adolescent Psychiatry and Psychotherapy, Central Institute

of Mental Health, University of Heidelberg, Mannheim, Germany; 7S.

Herzog Memorial Hospital, Research Department, Jerusalem, Israel;8Department of Developmental and Educational Psychology,

University of Valencia, Valencia, Spain; 9University Clinic for Child

and Adolescent Psychiatry, Essen, Germany; 10Department of

Experimental Clinical and Health Psychology, Ghent University,

Ghent, Belgium; 11Child and Adolescent Psychiatry, University of

Gottingen, Gottingen, Germany; 12Department of Clinical

Neuropsychology, Vrije Universiteit, Amsterdam, The Netherlands;13School of Psychology, Institute for Disorder on Impulse and

Attention, University of Southampton, Southampton, UK; 14Child

Study Center, New York University, New York, NY, USA;15Department of Child and Adolescent Psychiatry, University of


123

Zurich, Zurich, Switzerland; 16Child and Adolescent Clinical

Psychology, Institute of Psychology, University of Basel,

Switzerland; 17Child and Adolescent Psychiatry-Region Nordjylland

Aalborg Psychiatric Hospital Aarhus, University Hospital Aalborg,

Aalborg, Denmark; 18Department of Neuroscience, SUNY Upstate

Medical University, Syracuse, New York, USA; 19Department of

Psychiatry, SUNY Upstate Medical University, Syracuse, New York,

USA; 20Department of Cognitive Neuroscience, Donders Institute for

Brain, Cognition and Behavior, Radboud University Nijmegen

Medical Center, Nijmegen, The Netherlands

*To whom correspondence should be addressed.�The first, second and third author should be regarded as joint First

Authors.

Introduction, objectives: Developmental Coordination Disorder

(DCD) and ADHD share etiological background. A genome-wide

association study (GWAS) of motor coordination problems was per-

formed in a sample of children with ADHD.

Methods: 890 children participating in the IMAGE study were

evaluated by means of the PACS interview and motor questionnaires

(DCD-Q). Genetic association testing was performed in PLINK.

Results: Although none of the findings reached genome-wide sig-

nificance, bioinformatics analysis of the 97 gene-based top findings

revealed enrichment of genes involved in motor neuropathy, Amyo-

trophic Lateral Sclerosis (ALS), long term synaptic depression and

nervous system development and function. Eight out of the nine top

genes formed a network involved in both neurite outgrowth and basic

muscle function. Among the top findings was MAP2K5, a gene for

Restless Legs Syndrome. Twenty-four of 59 top-SNPs tested also

showed nominal association with DCD-Q (sub-)scales, allowing

further delineation of the etiologic mechanisms.

Conclusion: This first GWAS of motor coordination problems

detected interesting new candidate genes for further analysis,

including genes known to be involved in other movement disorders.

The findings may give additional clues about the etiology of motor

coordination problems.

Differential expression of the serotonin transporter

(SERT) and the dopamine transporter (DAT)

on developing platelets

Sarah Hohmann1, Nina Schweinfurth2, Tobias Banaschewski1,Patrick Schloss2

1Department of Child and Adolescent Psychiatry and Psychotherapy,

Central Institute of Mental Health, Mannheim, Germany;2Biochemistry Lab, Department of Psychiatry and Psychotherapy,

Central Institute of Mental Health, Mannheim, Germany

Introduction and objective: Many psychopharmacological drugs

(e.g. methylphenidate) target monoaminergic transporters as the

serotonin- and the dopamine-transporter and lead to an alteration in

the cell-surface expression of those proteins. As correlations between

the expression of transporters on neuronal cells and on blood platelets

were reported, we consider blood platelets an easy accessible system

for studying the regulation of expression-density of monoamine-

transporters due to medication. As platelets are not able to perform

protein-synthesis, we were interested in the expression of SERT and

DAT on megakaryocytes during thrombopoiesis.

Methods: We established an in-vitro cell system by using a human

megakaryoblastic cell-line (MEG01) and studied the influence of

several differentiation-supplements on platelet development and cell

surface expression of SERT and DAT. As methods we used immu-

nocytochemistry, flow-cytometry and a transcriptome analysis

concerning SERT and DAT.

Results/discussion: We report the impact of several differentiation-

supplements on thrombopoiesis as well as on cell-surface expression

the transporter molecules. Our now well characterized system enables

us to study the influence of methylphenidate on cell surface expres-

sion of transporter molecules on platelets and megakaryocytes as well

as on the synthesis of the different transporter proteins on a cellular

level, respectively.

Keywords: Monoaminergic transporters, Blood platelets, Methyl-

phenidate, Thrombopoiesis, Flow cytometry

Parental history of substance abuse moderates

the impact of stimulant treatment for ADHD on later

substance use

Iliyan Ivanov1, Seth C. Harty2,3, Carlin J. Miller4, Robyn Powers2,Dana Barowsky3, Jeffrey H. Newcorn1, Jeffrey M. Halperin1,2,3

1Division of Child and Adolescent Psychiatry, Mount Sinai School of

Medicine, New York, USA; 2Queens College of the City University

of New York, Department of Psychology, New York, USA; 3CUNY

Graduate Center, Neuropsychology Doctoral Program, New York,

USA; 4University of Windsor, Department of Psychology, Windsor,

Canada

Introduction and objective: To examine the extent to which psy-

chostimulant treatment in childhood interacts with parental history of

substance use in respect to adolescent substance use outcome in urban

youth with attention-deficit/hyperactivity disorder (ADHD).

Methods: Eighty adolescents were evaluated during childhood and

followed 9.30 (SD = 1.65) years later. Medication treatment history

was coded dichotomously as a function of stimulant use and subdi-

vided the sample in two groups: stimulant treated for more than

1 year (n = 52), and never treated (n = 28). Parent history of sub-

stance abuse was included as predictor variable to determine whether

the presence/absence of this factor differentially affected the outcome

of treated and untreated children.

Results: There were no significant differences in SUD or severity of

substance use as a function of medication history. However, there was

a significant parental history-by-medication status interaction such

that youth with ADHD + parental history who received stimulants

exhibited higher scores on measures of substance abuse severity in

adolescence.

Conclusion: Results indicate that parental history of substance use/

abuse may moderate the relationship between medication treatment

and substance use outcomes in youth with ADHD.

References

1. Barkley RA, Fischer M, Smallish L, Fletcher K (2003) Does the

treatment of attention-deficit/hyperactivity disorder with stimu-

lants contribute to drug use/abuse? A 13-year prospective study.

Pediatrics 111:97–109

2. Elkins IJ, McGue M, Iacono WG (2007a, b) Prospective effects

of attention-deficit/hyperactivity disorder, conduct disorder, and

sex on adolescent substance use and abuse. Arch Gen Psychiatry

64:1145–1152

3. Kendler KS, Schmitt E, Aggen SH, Prescott CA (2008) Genetic

and environmental influences on alcohol, caffeine, cannabis, and

nicotine use from early adolescence to middle adulthood. Arch

Gen Psychiatry 65:674–682


123

DISC1 copy number variation in ADHD

K.K. Jacobsen1,2, S. Johansson1,2, P.M. Knappskog2, J. Haavik1

1Department of Biomedicine, University of Bergen, Bergen, Norway;2Center for Medical Genetics and Molecular Medicine, Haukeland

University Hospital, Bergen, Norway

Introduction: At least 50% of children with ADHD continue to show

symptoms as adults, possibly representing a more severe phenotype.

Recently, it has been shown that submicroscopic copy number vari-

ations (CNVs) are important causes of genetic variation between

individuals [1]. 18 samples from our case–control study were previ-

ously genotyped on microarrays. One individual had a duplication in

DISC1, a gene known from other neuropsychiatric disorders such as

schizophrenia and biopolar disorder [2]. We wanted to determine the

frequency of this deletion in our material.

Materials and methods: A total number of 552 cases and 674 con-

trols were genotyped using a real time CNV assay targeted to DISC1.

Results: The frequency was 8/552 in cases and 14/674 in controls,

yielding a p value of 0.52 (OR 0.70, 95% CI 0.30–1.64).

Discussion: Although no significant difference was found between

cases and controls, DISC1 is still an interesting gene in neuropsy-

chiatry, as it has been shown to be important for neurodevelopment.

Studies of known DISC1 mutations have shown deficit in sustained

attention and patients with ADHD-like symptoms.

Conclusion: Further studies of DISC1 in ADHD are needed.

References

1. Tam et al (2009) The role of DNA copy number variation in

schizophrenia. Biol Psychiatry 66(11):1005–1012

2. Chubb et al (2008) The DISC locus in psychiatric illness. Mol


Genotype link with extreme antisocial behavior:

the contribution of cognitive pathways

Kate Langley1,2, Jon Heron3, Michael C. O’Donovan1,2,Michael J. Owen1,2, Anita Thapar1,2

1Department of Psychological Medicine and Neurology, School of

Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK;2MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff

University, Cardiff, UK; 3ALSPAC, Department of Social Medicine,

University of Bristol, Bristol, UK

As genes associated with neuropsychiatric disorders are increasingly

identified, we need to progress from observing associations to identi-

fying risk pathways. Investigating intermediate phenotypes, such as

cognitive performance, might elucidate such pathways. However there

is a need to show that genotype, intermediate phenotype and clinical

outcome lie on the same risk pathway [1]. The high activity COMTgenotype, in the presence of ADHD is associated with extreme anti-

social behavior [2] and in a cohort of 4365 children we test whether two

putative intermediate phenotypes, social understanding and executive

control lie on the risk pathway. We replicate the COMT high activity

genotype association with extreme antisocial behavior (OR = 2.82,

95% CI 2.02, 3.94, p \ 0.001 for the most severe antisocial behavior).

Of the putative intermediate phenotypes, impaired social understanding

but not executive control lies on the risk pathway from genotype to

antisocial behavior. The findings demonstrate the importance of testing

links between genotype, intermediate phenotype and clinical outcome in

the same sample to identify potential risk pathways.

References

1. Walters JTR, Owen MJ (2007) Endophenotypes in psychiatric

genetics. Molecular Psychiatry 12(10):886–890

2. Caspi A, Langley K, Milne B, Moffitt TE, O’Donovan M C,

Owen MJ et al (2008) A replicated molecular genetic basis for

subtyping antisocial behavior in children with attention-deficit/

hyperactivity disorder. Arch Gen Psychiatry 65(2):203–210

Is there a relation between 2D:4D fetal testosterone

marker and multidimensional attentional abilities

in children with ADHD?

Jurgen Lemiere1, Bart Boets2, Marina Danckaerts1

1Child and Adolescent Psychiatry, UPC-KULeuven, Leuven,

Belgium; 2Centre for Parenting, Child Welfare and Disabilities-

ExpORL, Department of Neurosciences KULeuven, Leuven, Belgium

Introduction and objective: This study examined the hypothesis that

prenatal testosterone exposure is implied in the aetiology of ADHD.

Our study is the first one that examined the association between

2D:4D digit ratio (a marker of fetal testosterone exposure) and the

presence of ADHD-related cognitive and behavioural problems in

children with ADHD and typically developing controls.

Methods: Sixty-four children with ADHD (mean age 8.8, SD 1.8) and

46 normal controls (mean age 9.2, SD 1.10) were included. Digit ratios

were measured twice by two independent raters. The Child BehaviourChecklist and the Test of Everyday Attention for Children were used to

assess behavioural problems and different aspects of attention.

Results: Digit ratio did not show the postulated relation with cogni-

tive and behavioural aspects of ADHD. Moreover, no group

differences in 2D:4D were observed between children with (a specific

subtype of) ADHD and control children.

Discussion and conclusion: Our findings contradict previous studies

that found evidence for masculinized digit ratios in children with

ADHD and therefore, challenge the hypothesis that fetal testosterone

exposure plays a prominent role in the aetiology of ADHD.

References

1. de Bruin EI, Verheij F, Wiegman T, Ferdinand RF (2006)

Differences in finger length ratio between males with autism,

pervasive developmental disorder-not otherwise specified, ADHD,

and anxiety disorders. Dev Med Child Neurol 48:962–965

2. Martel MM, Gobrogge KL, Breedlove SM, Nigg JT (2008)

Masculinized finger-length ratios of boys, but not girls, are

associated with attention-deficit/hyperactivity disorder. Behav

Neurosci 122:273–281

3. McFadden D, Westhafer JG, Pasanen EG, Carlson CL, Tucker

DM (2005) Physiological evidence of hypermasculinization in

boys with the inattentive type of attention-deficit/hyperactivity

disorder (ADHD). Clin Neurosci Res 5:233–245

Perinatal risk factors interacting with catechol

O-methyltransferase and the serotonin transporter gene

predict ASD symptoms in children with ADHD

Judith S. Nijmeijer1, Catharina A. Hartman1, Nanda N.J.Rommelse2,3, Marieke E. Altink2,4, Cathelijne J.M. Buschgens2,Ellen A. Fliers2,5, Barbara Franke2,6, Ruud B. Minderaa1,Johan Ormel1, Joseph A. Sergeant3, Frank C. Verhulst7,Jan K. Buitelaar2,4, Pieter J. Hoekstra1


123

Abstract: Given the previously found familiality of ASD symptoms

in children with ADHD, addressing ASD symptoms may be useful for

genetic association studies. We therefore studied the association of

the catechol O-methyltransferase (COMT) Val158Met and the sero-

tonin transporter (SLC6A4/SERT/5-HTT) 5-HTTLPR insertion/

deletion polymorphisms with ASD symptoms as measured by the

Children’s Social Behavior Questionnaire (CSBQ) in children with

ADHD, and the interaction of these polymorphisms with maternal

smoking during pregnancy and low birth weight. Analyzes were

performed on 207 Dutch participants of the International Multicenter

ADHD Genetics (IMAGE) study, and repeated in an independent

ADHD sample (n = 439) selected from the TRracking Adolescents’

Individual Lives Survey (TRAILS). No significant main effects of

COMT Val158Met, 5-HTTLPR, maternal smoking during pregnancy

and low birth weight were found. The COMT Val/Val genotype

interacted with maternal smoking during pregnancy in increasing

stereotyped behavior in the IMAGE sample (p = 0.008). This inter-

action reached significance in the TRAILS sample after correction for

confounders (p = 0.02). In the IMAGE sample, the 5-HTTLPR S/S

genotype interacted with maternal smoking during pregnancy,

increasing problems in social interaction (p = 0.02), and also inter-

acted with low birth weight, increasing rigid behavior (p = 0.03).

Findings for 5-HTTLPR in the TRAILS sample were similar. These

findings suggest gene–environment interaction effects on ASD

symptoms in children with ADHD.

Keywords: Attention-deficit/hyperactivity disorder, Autism spectrum

disorder, Gene environment, 5-HTT, COMTSubmitted at JCPP.

Identifying loci for the overlap between ADHD

and ASD using a genome-wide QTL linkage approach

J.S. Nijmeijer, Alejandro Arias-Vasquez, Nanda N.J. Rommelse,Marieke E. Altink, Richard J.L. Anney, Philip Asherson,Tobias Banaschewski, Cathelijne J.M. Buschgens, Ellen A. Fliers,Michael Gill, Ruud B. Minderaa, Luise Poustka, Joseph A. Sergeant,Jan K. Buitelaar, Barbara Franke, Richard P. Ebstein, Ana Miranda,Fernando Mulas, Robert D. Oades, Herbert Roeyers,Aribert Rothenberger, Edmund J.S. Sonuga-Barke,Hans-Christoph Steinhausen, Stephen. V. Faraone,Catharina A. Hartman, Pieter J. Hoekstra

Objective: The genetic basis for autism spectrum disorder (ASD)

symptoms in children with attention-deficit hyperactivity disorder

(ADHD) was addressed using a genome-wide linkage approach.

Method: Participants of the International Multi-Center ADHD Genetics

study comprising 1,143 probands with ADHD and 1,453 siblings were

analyzed. The total and subscale scores of the Social Communication

Questionnaire (SCQ) were used as quantitative traits for multipoint

regression-based linkage analyses on 5,407 autosomal single-nucleotide

polymorphisms applying MERLIN-regress software, both without and

with inclusion of ADHD symptom scores as covariates.

Results: The analyses without ADHD symptom scores as covariates

resulted in three suggestive linkage signals, i.e., on chromosomes

15q24, 16p13, and 18p11. Inclusion of ADHD symptom scores as

covariates resulted in additional suggestive loci on chromosomes

7q36 and 12q24, whereas the LOD score of the locus on chromosome

15q decreased below the threshold for suggestive linkage. The loci on

7q, 16p, and 18p were found for the SCQ restricted and repetitive

subscale, that on 15q was found for the SCQ communication subscale,

and that on 12q for the SCQ total score.

Conclusions: Our findings suggest that QTLs identified in this study

are ASD specific, although the 15q QTL potentially has pleiotropic

effects for ADHD and ASD. This study confirms that genetic factors

influence ASD traits along a continuum of severity, as loci potentially

underlying ASD symptoms in children with ADHD were identified

even though subjects with autism had been excluded from the

IMAGE sample, and supports the hypothesis that differential genetic

factors underlie the three ASD dimensions.

Keywords: ADHD, ASD, Linkage, Comorbidity

Submitted at JAACAP.

ADHD in adults: brain morphology and cognitive

testing as intermediate phenotypes for use in genetic

studies

Marten Onnink, Martine Hoogman, Cees C. Kan,Dorine I.E. Slaats-Willemse, Roshan Cools, Esther Aarts,Marcel Zwiers, Jan K. Buitelaar, Barbara Franke

Department of Psychiatry, Radboud University Nijmegen Medical

Centre, Nijmegen, The Netherlands

Introduction and objectives: There is clear evidence that ADHD is

frequent in adulthood. Our hypothesis is that adult ADHD is the most

genetic form of ADHD and is genetically more homogeneous than

ADHD in children. The aims of this research program are to identify

the genes involved in persistent ADHD, and to delineate their mode of

action by studying their association with cognitive functions and brain

morphology in adults with ADHD.

Methods: The following cognitive domains are investigated: IQ,

executive functioning (fMRI task), response inhibition, attentional

control, working memory (fMRI task), delay aversion, temporal

processing and reward anticipation (fMRI task). In addition, we

obtain anatomical scans for measuring brain volumes (T1-weighted

MRI) and brain connectivity (DTI).

Results: Currently, we have enrolled 100 adult ADHD subjects and

[50 healthy controls.

Discussion: Despite the increasing recognition of adult ADHD, little

is known about cognitive deficits, brain anomalies and the genes

involved. In our studies we will investigate neurotransmission-related

genes (such as DRD4 and DAT1) but also new candidates (such as

CDH13 and LPHN3).

Conclusion: Our large, well-characterized sample of adult ADHD

patients in combination with our intermediate phenotype approach

has great potential for increasing knowledge of persistent ADHD.

Keywords: Adult ADHD, Genetics, Intermediate phenotype, Neu-

ropsychology, Neuroimaging, Connectivity

Attention-deficit/hyperactivity disorder (ADHD)

phenotype is influenced by catechol-O-

methyltransferase (COMT) and psychosocial risk

factors

H. Palmason1,4, D. Moser1, J. Sigmund1, C. Vogler1, S. Hanig2,A. Schneider2, C. Seitz2, A. Marcus3, J. Meyer1, C. Freitag2

1Graduate School of Psychobiology, Department of Neuro-Behavioral

Genetics, University of Trier, Trier, Germany; 2Department of Child

and Adolescent Psychiatry and Psychotherapy, Saarland University

Hospital, Homburg, Germany; 3Department of Child and Adolescent

Psychiatry, Das Mutterhaus der Borromaerinnen, Trier, Germany;4Department of Child and Adolescent Psychiatry, Landspitali

National Hospital, Reykjavik, Iceland


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Introduction and objective: The COMT gene plays a crucial role in

the metabolism of catecholamines in the frontal cortex [1]. A single

nucleotide polymorphism (Val158Met SNP) leads to either methionine

(Met) or valine (Val) at codon 158, resulting in a three- to fourfold

reduction in COMT activity [2]. The aim of the present study was to

look at gene–environment interaction in ADHD.

Methods: Assess the COMT Val158Met SNP as a risk factor for

ADHD, ADHD symptom severity and co-morbid conduct disorder

(CD) in 166 children with ADHD.

Results: The Met allele of the COMT Val158Met SNP was associated

with ADHD and increased ADHD symptom severity. No association

with co-morbid CD was observed. In addition, ADHD symptom

severity and early adverse familial environment were positive pre-

dictors of lifetime CD.

Discussion: These findings support previous results implicating

COMT in ADHD symptom severity and early adverse familial

environment as risk factors for co-morbid CD.

Conclusion: These results emphasize the need for early intervention

to prevent aggressive and maladaptive behaviour progressing into

CD, reducing the overall severity of the disease burden in children

with ADHD.

References

1. Grossman M, Emanuel B, Budarf M (1992) Chromosomal

mapping of the human catechol-O-methyltransferase gene to

22q11.1-q11.2. Genomics 12:822–825

2. Weinshilboum R, Otterness D, Szumlanski C (1999) Methylation

pharmacogenetics: catechol-O-methyltransferase, thiopurine

methyltransferase, and histamine N-methyltransferase. Annu

Rev Pharmacol Toxicol 9:19–52

Integrated genome-wide association findings implicate

a neurodevelopmental network involved in neurite

outgrowth in attention deficit hyperactivity disorder

(ADHD)

Geert Poelmans1*, David L. Pauls2, Jan K. Buitelaar3,Barbara Franke1,4


Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen,

The Netherlands; 2Psychiatric and Neurodevelopmental Genetics

Unit, Center for Human Genetic Research, Massachusetts General

Hospital, Harvard Medical School, Boston, USA; 3Department of

Cognitive Neurosciences, Donders Institute for Brain, Cognition and


The Netherlands; 4Department of Human Genetics, Radboud

University Nijmegen Medical Centre, Nijmegen, The Netherlands

*Presenting author

Introduction and objectives: Attention deficit hyperactivity disorder

(ADHD) is a common and highly heritable neuropsychiatric disorder

observed in children and adults. We have investigated the presence of

genomic convergence in the top findings of the five published gen-

ome-wide association studies (GWAS) of ADHD.

Methods: We conducted bioinformatics analyses and a systematic

literature analysis of 85 ADHD candidate genes from the five GWAS

that contained at least one single nucleotide polymorphism (SNP)

yielding an association P value \ 1.00E-04.

Results and discussion: We found that 44 of the 85 top ADHD

candidate genes fit into a network that links several neuronal cell

membrane proteins with downstream-acting adaptor proteins and

neuronal cytoskeleton/extracellular matrix associated proteins. Acting

together, these proteins are involved in directed neurite outgrowth.

Moreover, a number of proteins in the identified network are directly

modulated by stimulants, the most commonly used psychopharma-

cological treatment for ADHD.

Conclusion: We have identified a protein network that may provide

an important contribution to our understanding of the molecular basis

of ADHD and give clues to specific genes that should be tested in

future studies.

Keywords: ADHD, Genome-wide association studies, Bioinformat-

ics, Neurite outgrowth, Stimulants

Genetic associations between ADHD symptoms

and cognitive measures

Tinca J.C. Polderman1,2, Anja C. Huizink2, Dorret I. Boomsma1,Frank C. Verhulst2, Meike Bartels1

1VU University, Department of Biological Psychology, Van de

Boechorststraat 1, 1081 BT Amsterdam, The Netherlands; 2Erasmus

Medical Center, Sophia Child Hospital, Department of Child and

Adolescent Psychiatry, Rotterdam, The Netherlands

Introduction: ADHD is a highly heritable disorder but gene finding

studies have been unsuccessful so far. Cognitive traits like executive

functions, IQ and academic achievement measures have been asso-

ciated to ADHD. These associations may direct to biological

mechanisms, and related genes, that are involved in ADHD.

Methods: The current study investigated the etiology of the relation

between ADHD related symptoms and educational achievement.

Subjects were 568 Dutch twin pairs. Maternal ratings on ADHD

symptoms were assessed at age 5 and at age 7. Academic achieve-

ment was measured with standardized tests on mathematics,

comprehension, reading and spelling in grade 2, 4 and 6.

Results: Results show that ADHD related symptoms correlated

around -0.20 with comprehension and mathematics, and around

-0.12 with reading and spelling on a phenotypic level. Phenotypic

correlations were predominantly determined by genetic factors;

environmental factors did not contribute to the association.

Discussion and conclusion: Previous studies reported genetic asso-

ciations between IQ and ADHD related symptoms. The genetic overlap

in ADHD and cognitive measures shows that cognitive abilities should

be taken into account regarding etiological factors of the disorder.

Keywords: ADHD symptoms, Cognition, Genetics, Twin study,

Children

Genetic variants of KCNJ6 influence activation

of the anterior cingulate cortex in ADHD

but not in healthy probands

T.J. Renner1*, A.C. Ehlis2*, C. Roser2, C. Jacob2, M. Gerlach1,A. Warnke1, K.P. Lesch2, A.J. Fallgatter2

1University of Wurzburg, Department of Child and Adolescent

Psychiatry, Psychosomatics and Psychotherapy, Wurzburg, Germany;2University of Wurzburg, Department of Psychiatry, Psychosomatics

and Psychotherapy, Wurzburg, Germany

*Presenting author

Introduction and objective: In imploring mutual genetics of sub-

stance use disorders and ADHD, KCNJ6, encoding the potassium

channel subunit 2, associated with nicotine abuse [1], is an interesting

candidate. We investigated the influence of two promoter


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polymorphisms on Anterior Cingulate Cortex (ACC) activation in an

adult German ADHD sample.

Methods: EEGs of 218 German adults affected by ADHD and 118

healthy probands were recorded during a cued Continuous Perfor-

mance Test. Centroid locations and NoGo-Anteriorization (NGA), as

well as genotypes of rs6517442 and rs7275707 were determined.

Statistical analysis comprised ANOVAs and post hoc t tests.

Results: Influence of rs6517442 and rs7275707 on both, Go and Nogo

centroids was found specifically in the ADHD-group.

Discussion: Influence of both investigated KCNJ6 promoter SNPs on

Go and Nogo centroids was found in adult ADHD patients, but not in

healthy probands. This result implies interplay of KCNJ6 and ADHD-

relevant factors, altering brain activation in ADHD.

Conclusion: The results implicate a role of KCNJ6, involved in

pathophysiologically relevant neurosystems [2], in ADHD. Our

findings may support efforts of identifying ADHD endophenotypes

modulated by KCNJ6 with respect to ACC activation [3].

References

1. Saccone SF, Hinrichs AL, Saccone NL, Chase GA, Konvicka K,

Madden PA, Breslau N, Johnson EO, Hatsukami D, Pomerleau O,

Swan GE, Goate AM, Rutter J, Bertelsen S, Fox L, Fugman D,

Martin NG, Montgomery GW, Wang JC, Ballinger DG, Rice JP,

Bierut LJ (2007) Cholinergic nicotinic receptor genes implicated

in a nicotine dependence association study targeting 348

candidate genes with 3713 SNPs. Hum Mol Genet 16(1):36–49

2. Cruz HG, Berton F, Sollini M, Blanchet C, Pravetoni M,

Wickman K, Luscher C (2008) Absence and rescue of morphine

withdrawal in GIRK/KIR3 knock-out mice. J Neurosci

28(15):4069–4077

3. Stippekohl B, Winkler M, Mucha RF, Pauli P, Walter B, Vaitl D, Stark

R (2010) Neural responses to begin- and end-stimuli of the smoking

ritual in nonsmokers, nondeprived smokers, and deprived smokers.

Neuropsychopharmacology. 2010 Jan 20. [Epub ahead of print]

The role of rare variants of DRD4 gene in ADHD:

Brazilian sample also suggests major effect of allelic

heterogeneity

L. Tovo-Rodrigues1, L.A. Rohde2, J.P. Genro1, C. Zeni2,G.V. Polanczyk3, T. Roman1, M. Schmitz2, F.Z.C. Marques1,V. Contini1, E.H. Grevet2, P. Belmonte-de-Abreu2, H.D. Bau1,M.H. Hutz1

1Department of Genetics, Instituto de Biociencias, Universidade

Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; 2ADHD

Outpatient Clinic, Hospital de Clınicas de Porto Alegre, Porto Alegre,

RS, Brazil; 3Department of Psychiatry, University of Sao Paulo

Medical School and National Institute for Developmental Psychiatry,

Sao Paulo, Brazil

The third exon of DRD4 gene contains a VNTR of 48 bp and dif-

ferences of single nucleotide polymorphism inside these repeats.

Seven repeat allele has been proposed as a susceptibility allele for

ADHD. However, association studies showed conflicting results.

Considering mutation sites into the VNTR, an excess of rare variants

has been observed in ADHD probands. The aim of this study was to

verify if ADHD patients were more variable than controls in the third

exon of DRD4. Sample is composed by 66 ADHD and 37 control

individuals homozygous for the 7R and 4R alleles. After sequencing,

a total of 17 haplotypes were observed. No difference for 4R distri-

bution was observed between groups while for 7R, ADHD patients

showed an excess of rare haplotypes when compared with controls

(P = 0.031). ADHD patients also showed more non-synonymous

mutations than controls considering 7R alleles (P = 0.043). These

results provide additional support for the hypothesis that allelic het-

erogeneity at the DRD4 VNTR is playing a role in the association

with ADHD. Considering 7R rare variants could be important to

determine ADHD risk.

COMT gene and ADHD: genetic susceptibility

and pharmacogenetics

A. Salatino-Oliveira1, J.P. Genro1, A.P. Guimaraes1, C. Zeni2,G. Polanczyk3, T. Roman1, L.A. Rohde2, M.H. Hutz1

1Department of Genetics, Federal University of Rio Grande do Sul,

Porto Alegre, Brazil; 2Department of Psychiatry, Federal University

of Rio Grande do Sul, Porto Alegre, Brazil; 3Department of

Psychiatry, University of Sao Paulo Medical School and National

Institute for Developmental Psychiatry, Sao Paulo, Brazil

The COMT enzyme catalyzes the degradation pathway of catechola-

mines. The Val158Met is a functional polymorphism and it consists of a

G to A mutation on MB-COMT resulting in a Valine to Methionine

substitution. This study tested whether COMT gene is associated with

the presence of DBDs in children with ADHD, and with clinical

improvement of oppositional symptoms with ADHD boys treated with

MPH. 473 Children were evaluated and boys whose data on response

to MPH for at least the first month of treatment were invited to join the

study. Val/Val genotype is more frequent (+16%) among children with

ADHD and DBDs than other children (p = 0.017). A significant

interaction effect between the COMT genotype and treatment over

time was observed (p = 0.021). Children with ADHD and Val/Val

genotype seem to be more susceptible to develop DBDs than Met

carriers. ADHD boys with Met allele treated with MPH have a higher

improvement on oppositional symptoms. Therefore, this study high-

lights the importance of genetic susceptibility on childhood-onset

antisocial behavior and emphasizes the role of the COMT gene in

clinical improvement in oppositional symptoms.

References

1. Thapar A, Langley K, Fowler T, Rice F, Turic D, Whittinger N,

Aggleton J, Van den Bree M, Owen M, O’Donovan M (2005)

Catechol O-methyltransferase gene variant and birth weight predict

early-onset antisocial behavior in children with attention-deficit/


2. Caspi A, Langley K, Milne B, Moffitt TE, O’Donovan M, Owen

MJ, Polo Tomas M, Poulton R, Rutter M, Taylor A, Williams B,

Thapar A (2008) A replicated molecular genetic basis for

subtyping antisocial behavior in children with attention-deficit/


3. Fowler T, Langley K, Rice F, van den Bree MB, Ross K,

Wilkinson LS, Owen MJ, O’Donovan MC, Thapar A (2009)

Psychopathy trait scores in adolescents with childhood ADHD:

the contribution of genotypes affecting MAOA, 5HTT and

COMT activity. Psychiatr Genet 19(6):312–319

Association between the DAT1 gene and the inattentive

subtype of attention deficit hyperactivity disorder

Chi-Yung Shang1,2, Susan Shur-Fen Gau1,2

1Department of Psychiatry, College of Medicine, National Taiwan

University, Taipei, Taiwan; 2Department of Psychiatry, National

Taiwan University Hospital, Taipei, Taiwan


123


(ADHD) is a common psychiatric disorder with a large genetic

component [1]. We tested the hypothesis that the dopamine trans-

porter gene (DAT1) was associated with ADHD.

Methods: In this family based study, we recruited 273 Chinese pro-

bands diagnosed with ADHD by DSM-IV criteria, and their family

members. 14 single nucleotide polymorphism (SNP) markers across

this gene and the variable number of tandem repeat (VNTR) poly-

morphism in 30-untranslated region (30UTR) were genotyped.

Results: Calculations of pairwise linkage disequilibrium revealed

three main haplotype blocks (HB): HB1 (intron 2 through intron 6),

HB2 (intron 8 through intron 11), and HB3 (30UTR). The haplotype

rs27048 (C)/rs429699 (T) was significantly associated with the inat-

tentive subtype (P = 0.008).

Discussion: Our findings indicate that the haplotype rs27048 (C)/

rs429699 (T) is a novel genetic marker in the inattentive ADHD subtype.

Conclusion: These results suggest that variation in the DAT1 gene

may primarily affect the inattentive subtype of ADHD [2].

References

1. Faraone SV et al (2005) Molecular genetics of attention deficit

hyperactivity disorder. Biol Psychiatry 57:1313–1323

2. Krause KH et al (2003) The dopamine transporter and neuroim-

aging in attention deficit hyperactivity disorder. Neurosci

Biobehav Rev 27:605–613

Visual memory as an endophenotype in attention-deficit

hyperactivity disorder: evidence from the Cambridge

neuropsychological test battery

Susan Shur-Fen Gau, Chi-Yung Shang

Department of Psychiatry, National Taiwan University Hospital and

College of Medicine, Taipei, Taiwan

Introduction and objective: There is lack of data regarding visual

memory as and cognitive endophenotype for ADHD, which was

evaluated in this work.

Methods: We assessed the visual memory of 279 probands with

DSM-IV ADHD, aged 11–17 years old, 108 unaffected siblings, and

173 unaffected school controls (all IQ [ 80) by using the Delayed

Matching to Sample (DMS), Pattern Recognition Memory (PRM),

and Paired Associates Learning (PAL) of the CANTAB.

Results: Probands with ADHD and unaffected siblings performed

poorer in the DMS with increased magnitudes of group differences in

the DMS as the task difficulties increased even after controlling for

IQ, comorbidity, use of methylphenidate, and demographics. Pro-

bands with ADHD but not unaffected siblings performed worse than

controls in the PRM and PAL tasks. Persistent ADHD and use of

methylphenidate were associated with more severe visual memory

deficits.

Discussion: Children and adolescents with ADHD may have impaired

visual memory that is associated with the persistence of current

ADHD symptoms.

Conclusion: The finding indicates that visual memory measured by

the DMS may be a useful endophenotype for genetic studies of

ADHD.

References

1. Doyle AE, Willcutt EG, Seidman LJ et al (2005) Attention-

deficit/hyperactivity disorder endophenotypes. Biol Psychiatry

57:1324–1335

2. Gau SS, Shang CY (2010) Executive functions as endophenotypes in

ADHD: evidence from the Cambridge Neuropsychological Test

Battery (CANTAB). J Child Psychol Psychiatry 2010 Jan 18. [Epub

ahead of print]

Poster Sessions D: Reward Processing

Cognitive control under reward and non-reward

conditions in children and adolescents with ADHD:

an fMRI-study

D.Baeyens1,2,3, M.J. Mulder1, H. Roeyers2, H. van Engeland1,S. Durston1,4

1Rudolf Magnus Institute of Neuroscience, Department of Child and

Adolescent Psychiatry, Neuroimaging Lab, HP A 01.468, University

Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht,

The Netherlands; 2Department of Psychology, Developmental

Disorders, Faculty of Psychology and Educational Sciences, Ghent

University, Henri Dunantlaan 2, 9000 Ghent, Belgium; 3CODE

Lessius, Research group Developmental Disorders, Lessius

University College, Katholieke Universiteit Leuven Association,

Sanderusstraat 45, 2018 Antwerp, Belgium; 4Sackler Institute for

Developmental Psychobiology, Weill Medical College of Cornell

University, 1300 York Avenue, Box 140, New York, NY 10021, USA

Introduction and objective: Cognitive deficits in ADHD may be

ameliorated by manipulating motivation using reward. We investi-

gated whether reward interacts with cognitive control in ADHD.

Methods: We used a go/no-go task where reward was parametrically

manipulated in a sample of 39 individuals with ADHD and 21 con-

trols, as well as in an event-related, rapid mixed-trial fMRI

experiment with 15 boys with ADHD and 15 controls.

Results: Behaviourally, on no-go trials, accuracy was significantly

lower for individuals with ADHD than for controls. There were no

group 9 reward interactions. FMRI results showed reduced IFG

activation in ADHD on no-go trials. ROI analyses showed increasing

activation in left caudate nucleus with reward for controls, but not for

boys with ADHD. No interaction between reward and cognitive

control was found.

Discussion: These findings replicate earlier work on cognitive

control deficits and decreased striatal response to reward cues in

ADHD. However, we found no interaction between reward and

inhibition.

Conclusion: These results suggest that deficits in cognitive control

remain a prominent feature of ADHD and cannot be (fully) com-

pensated by manipulating motivation.

Adult ADHD patients show reduced implicit attention

to positive stimuli: an examination of the early posterior

negativity

S.C. Biehl1, T. Schreppel, C. Jacob1, M. Heine1,A. Boreatti-Hummer1, A. Muhlberger2, A.J. Fallgatter1,M.J. Herrmann1,2

1Department of Psychiatry, Psychosomatics, and Psychotherapy,

University of Wurzburg, Wurzburg, Germany; 2Department of

Psychology, University of Wurzburg, Wurzburg, Germany

Introduction and objective: It is yet unclear whether deficits in

facial emotion processing in ADHD extend to the processing of

positive and negative stimuli that do not directly depict emotions. The


123

early posterior negativity (EPN) provides the possibility to analyse

emotional processing at a neurophysiological level.

Methods: Thirty-two adult patients with ADHD who were without

medication for 3 days before testing and 32 healthy controls mat-

ched for age and gender passively viewed 120 pictures (positive,

negative, neutral) from the International Affective Picture System

(IAPS). EEG was recorded from 21 electrodes placed according to

the extended international 10–20 system and the EPN was

calculated.

Results: We found significantly smaller EPNs in the group with

ADHD compared to healthy controls during the presentation of

positive stimuli.

Discussion: The results point to a deficit in the processing of positive

emotional stimuli and are unlikely to be caused by long-term medi-

cation or withdrawal.

Conclusion: The reduced EPN indicates a lack of implicit selective

attention to positive emotional stimuli and might further implicate a

deficient reward system in the aetiology of ADHD symptoms.

References

1. Da Fonseca D, Seguier V, Santos A, Poinso F, Deruelle C (2009)

Emotion understanding in children with ADHD. Child Psychiatry

Hum Dev 40(1):111–121

2. Schupp HT, Junghofer M, Weike AI, Hamm AO (2003)

Emotional facilitation of sensory processing in the visual cortex.

Psychol Sci 14(1):7–13

3. Sonuga-Barke EJ (2003) The dual pathway model of AD/HD: an

elaboration of neuro-developmental characteristics. Neurosci

Biobehav Rev 27(7):593–604

Measuring reward sensitivity in ADHD

Patrick de Zeeuw1, Sarah Durston1

1Department of Child and Adolescent Psychiatry, Rudolf Magnus

Institute of Neuroscience, University Medical Centre Utrecht,

Utrecht, The Netherlands

Introduction and objective: ADHD has been associated with

changes in reward sensitivity, but it is unclear which aspects

of reward processing are affected [1]. We aimed to investigate the

utility of response time distributions as a measure of reward

sensitivity.

Methods: A two-choice reaction time task was designed, rigged so

that rewarded trials were predetermined in two high reward frequency

(80%) and two low reward frequency (20%) blocks. Three trial types

were used: no reward, 5 cents (low) or 15 cents (high) reward. Sub-

jects guessed which of two SpongeBob characters was hiding a

wallet. The outcome measure was the shift of the response time

distribution between the reward conditions and the no-reward con-

dition for both frequencies.

Results: Children with ADHD showed a more prominent shift of the

response time distribution in the high frequency blocks, regardless of

the magnitude of reward (5 or 15 cents). Controls showed a shift in

both the high and low reward frequency blocks.

Discussion: Our results show that reward frequency is an important

factor in reward effectiveness in ADHD.

Conclusion: The shift of the response time distribution in high versus

low reward trials may be a useful measure of reward sensitivity in ADHD.

Reference




Temporal reward discounting in ADHD and ASD

Ellen Demurie1, Herbert Roeyers1, Edmund Sonuga-Barke1,2,Dieter Baeyens3

1Ghent University, Ghent, Belgium; 2University of Southampton,

Southampton, UK; 3Lessius University College, Antwerp, Belgium

Introduction and objective: As children with ADHD are aversive to

delayed reinforcement, steeper temporal discounting (TD) of delayed

rewards is hypothesized and found in this group. The current study

investigated whether discounting functions are disorder specific and

differ according to reward type.

Methods: Participants: 39 children (8–16 years) with ADHD, 34 chil-

dren with ASD, 46 controls. TD tasks: a monetary and an alternative

reward TD task (activities, food, material or social reinforcement) with

repeated choices between immediate (hypothetical) small variable

rewards and large constant rewards delivered after a variable delay.

Results: Monetary AUC in the ADHD group was significantly lower

than that of controls and the ASD group. Social reward AUC was

higher for controls compared to the ADHD group. AUC for money

was significantly higher compared to activities and edible rewards.

Conclusion: The group difference in hypothetical monetary rewards TD

suggests that children with ADHD have some insight into their delay

aversion behaviour. Furthermore, directly consumable reinforcers show

steeper TD than the conditioned reinforcer money. TD is probably not

only dependent on reward magnitude but also on specific reward nature.

Modulation of working memory in ADHD, effects

of reinforcement intensity and form

Sebastiaan Dovis1*, Saskia van der Oord1, Reinout Wiers2,Pier Prins1

1Department of Clinical Psychology, University of Amsterdam,

Amsterdam, The Netherlands; 2Department of Developmental

Psychology, University of Amsterdam, Amsterdam, The Netherlands

*Corresponding author: S. Dovis, Department of Clinical Psychology,

University of Amsterdam, Roetersstraat 15, 1018 WB Amsterdam,

The Netherlands. Tel.: +31-205256298; E-mail: [email protected]

Problems children with ADHD experience are thought to be the result of

deficits in executive functioning (EF). Spatial central executive working

memory (SCE WM) has been demonstrated to be the most impaired EF in

these children. Reinforcement models suggest that the poor performance

of children with ADHD on EF measures is not due to an underlying EF

deficit, but is caused by an altered reinforcement sensitivity. However,

studies that examine this altered reinforcement sensitivity in children with

ADHD show inconsistent results. These inconsistent findings may be

related to the heterogeneity in the reinforcement conditions of these studies

(different intensities and forms of reinforcement) [1, 2]. The present study

investigates the effects of different intensities and forms of reinforcement

on the SCE WM of 48 ADHD children and 48 controls aged 9–12 years.

For this we use a new SCE WM task in four reinforcement conditions

(feedback-only, a small amount of money (1 €), a large amount of money

(10 €], and a computer game version of the task). Preliminary results of

this study will be presented and implications will be discussed.

References




2. Luman M, Tripp G, Scheres A (2010) Identifying the neurobi-

ology of altered reinforcement sensitivity in ADHD: a review and

research agenda. Neurosci Biobehav Rev (in press)


123

The influence of cognitive control on reward choice

in ADHD

Catherine Fassbender1, Samuel M. McClure2, J. Faye Dixon1,Danielle Mizuiri1, Meghan Miller3, Dorothy Yip1,Julie B. Schweitzer1

1M.I.N.D. Institute, University of California Davis, Sacramento, CA,

USA; 2Department of Psychology, Stanford University, Stanford, CA,

USA; 3Department of Psychology, University of California Berkeley,

Berkeley, CA, USA

The ADHD is a heterogeneous disorder [1] with disruption in cognitive

control and reward processing, including preferences for small imme-

diate rewards [2]. We examined the relationship between delay

discounting (DD; k) measures of impulsivity and cognitive control in

ADHD. Participants, 11 ADHD and 8 controls (mean age 14.63 yrs),

completed processing speed (PS) and achievement measures, Parent’s

Conners’ Rating scale, a DD task (measure of k); acquired fMRI data on a

subset of ten participants (7 ADHD) on a cued flanker paradigm.

Regression tested predictors of impulsivity (k). Results suggest a rela-

tionship between reward sensitivity and cognitive control. Predictors of kdisplaying a negative relationship included Calculation ability, PS and

correct responses to cued incongruents. Hyperactivity/impulsivity rat-

ings and cued incongruent BOLD response positively predicted k; larger

k (greater impulsivity) associated with increased activation in left basal

ganglia, left occipital lobe, right precuneus and the cerebellar vermis.

Substrates of attention and reward valuation appear to be linked; ado-

lescents who engaged areas previously associated with ADHD and

methylphenidate administration [3], chose the immediate reward.

Reward-related and cognitive control impairments in ADHD are

synergistic.

References

1. Nigg JT et al (2005) Causal heterogeneity in attention-deficit/

hyperactivity disorder: do we need neuropsychologically

impaired subtypes? Biol Psychiatry 57(11):1224–1230



appraisal. Clin Psychol Rev 25(2):183–213

3. Schweitzer JB et al (2004) Effect of methylphenidate on

executive functioning in adults with attention-deficit/hyperactiv-

ity disorder: normalization of behavior but not related brain

activity. Biol Psychiatry 56(8):597–606

Cross-cultural considerations in conducting research

on reinforcement sensitivity and ADHD

E. Furukawa1, G. Tripp1, E. Caparelli-Daquer2, P. Mattos3

1Okinawa Institute of Science and Technology, Okinawa, Japan;2State University of Rio de Janeiro, Rio de Janeiro, Brazil; 3Federal

University of Rio de Janeiro, Rio de Janeiro, Brazil


(ADHD) affects children and adults across cultures. If ADHD is

biological in origin the disorder should be largely free of environ-

mental variances. However, cultural traditions and practices influence

how the disorder is perceived, assessed, expressed and treated. There

may also be cultural differences in the expectations of reward and

punishment influencing behavior and ADHD symptoms. Few studies

have been conducted using the same experimental paradigms across

multiple countries.

Method: We are currently examining sensitivity to reinforcement in

children with ADHD in Japan, Brazil and New Zealand.

Results: Technical and theoretical training in psychology and psy-

chiatry varies widely across the participating countries. Availability

of equivalent appropriate assessment tools is limited in Japan and

Brazil. Limited professional expertise/understanding contributes to

increased stigma. We have observed differences in use and perception

of positive reinforcement in Japan.

Discussion and conclusions: We believe that cross-cultural research

can contribute significantly to the advancement of knowledge in the

assessment and treatment of ADHD. It may also provide important insight

into the neurobiological and environmental contributors to ADHD.

Keywords: ADHD, Reinforcement sensitivity, Cross-cultural

comparisons

Cultural contributions to reinforcement sensitivity

E. Furukawa1, C. McAlpine2, B. Alsop2, K. Ito1, G. Tripp1,2

1Okinawa Institute of Science and Technology, Okinawa, Japan;2University of Otago, Wellington, New Zealand

Introduction: The neurobiology of reinforcement has been subject to

intense scientific study in recent years. In contrast, relatively little

attention has been paid to environmental and cultural influences.

Objective: To compare the sensitivity of normally developing Japanese

and New Zealand school children to changes in reward frequency.

Method: We are currently collecting data from Japanese elementary

school children using a signal detection task in which correct iden-

tification of one of two possible stimuli is reinforced more frequently

(4:1). The response alternative associated with the higher rate of

reinforcement changes twice during the task, each time after the

delivery of 20 reinforcers.

Results: Existing data from NZ children demonstrates response bias

(preference for the better alternative) tracks the changes in response

alternative offering the higher rate of reinforcement. We hypothesize

the performance of Japanese children on the same task will demon-

strate similar sensitivity to changing reinforcement contingencies.

Discussion and conclusions: Sensitivity to reinforcement contin-

gencies is assumed to be largely free of cultural influences. Findings

from the current study will indicate if this assumption holds true for

Japanese children.

Keywords: Signal detection, Reinforcement, Culture, Children

The effect of social motivation on interference control

in boys with ADHD and autism

Hilde M. Geurts1, Mariolein Luman2, Catharina S. van Meel3,4

1Department of Psychonomics, Universiteit van Amsterdam,

Amsterdam, The Netherlands; 2Department of Clinical

Neuropsychology, Vrije Universiteit, Amsterdam, The Netherlands;3Leiden Institute for Psychological Research, Leiden University,

Leiden, The Netherlands; 4Leiden Institute for Brain and Cognition,

Leiden University, Leiden, The Netherlands

Introduction and objective: Cognitive control deficits in children

with ADHD and with autism spectrum disorders (ASD) can be

reduced when motivation is increased through tangible reinforcers.

However, whether these deficits can also be modulated by non-tan-

gible reinforcers has hardly been studied.

Methods: The effect of social motivation (a simulated competition

with peers) on the ability to suppress irrelevant information (i.e.,


123

interference control) was investigated in 22 ADHD, 22 ASD, and 33

typically developing (TD) boys.

Results: All groups benefited from the motivation manipulation, i.e.,

their performance increased when they thought they were competing

with peers. Although the boys with ADHD were still slower than TD

boys when motivated, they performed as accurately as TD boys.

Children with ASD also improved slightly in accuracy and response

speed, but this was not significant.

Discussion and conclusion: Children with ADHD are able to exert

sufficient cognitive control when they are motivated, which is in line

with the current models of ADHD. However, motivation seems to

have a general effect on performance and is not solely related to

cognitive control abilities. In contrast, this effect was not obtained in

children with ASD.

Keywords: Autism, ADHD, Motivation, Cognitive control

Influence of candidate ADHD genes on reward

processing and working memory in adult ADHD

patients and healthy subjects

M. Hoogman1, E. Aarts1,2, M. Zwiers1,2, D. Slaats-Willemse1,3,R. Cools1,2, C. Kan1, J. Buitelaar1, B. Franke1,4



The Netherlands; 2Donders Institute (RU/DI-BCB), Radboud

University Nijmegen, Nijmegen, The Netherlands; 3Karakter Child

and Adolescent University Centre, Nijmegen, The Netherlands;4Department of Human Genetics, Radboud University Nijmegen

Medical Centre, Nijmegen, The Netherlands

Introduction and objectives: ADHD is a highly heritable disorder,

which is attributable to multiple genes of small effect size. Understanding

the modes of action of those genes already known can aid in unraveling

biological mechanisms underlying ADHD. For that goal we built a large

database of adult ADHD patients and controls extensively characterized

using cognitive testing and functional imaging.

Methods: We are currently focusing on functional genetic variants in

two ADHD genes, NOS1 and DRD4, and their effects on cognitive

and motivational functioning in ADHD.

Results: Reward-related impulsivity and striatal activity are influ-

enced by the NOS1 gene in ADHD patients (n = 69) and controls

(n = 29). Working memory performance was not affected by DRD4

genotype, but prefrontal cortex activity was.

Discussion: Our findings fit into a model in which ADHD genes act

via glutamatergic and dopaminergic/serotonergic systems (NOS1)

and signaling downstream of dopamine (DRD4) to affect brain

function in subcortical and cortical areas.

Conclusion: Functional effects of ADHD genes were more readily

observed when analyzing the activity of relevant brain structures than

at a behavioral level. We think this approach is an efficient way to

elucidate ADHDs biological mechanisms.

Keywords: Reward, Working memory, NOS1, DRD4, fMRI

Brain activation in preadolescent with low versus high

risk for subsequent substance abuse

Iliyan Ivanov1, Xun Liu1, Kurt Schulz1, Jin Fan1, Suzanne Clerkin1,Jeffrey M. Halperin1, Jeffrey H. Newcorn1

1Mount Sinai School of Medicine, New York, NY, USA

Introduction and objective: To evaluate the neurobiological basis

for addiction vulnerability using fMRI in drug naıve youth with

attention deficit/hyperactivity disorder (ADHD). We examined the

degree to which parental history of addiction contributes to BOLD

signal activation in the brain reward system.

Methods: Two groups of drug-naıve children with ADHD ages 8–

13 years were scanned while performing an event-related reward task.

High (N = 10) and low (N = 10) risk groups were established based

on the presence of parental history of addiction. The effects of

anticipation, conflict, and reward were tested by applying appropriate

linear contrasts, resulting in six contrast maps. A separate regressor

for parental history of addiction was added. Results are reported at an

uncorrected threshold p \ 0.01 and a cluster threshold j C 100

voxels.

Results: Reward cue/outcome trials activated anterior cingulate gyrus

(ACG), ventral striatum and insula in all subjects. The HR group

additionally exhibited increased activation in orbito-frontal cortex,

right insula and ACG during the same trials.

Discussion: These results suggest that parental history of addiction

may be associated with altered sensitivity to reward cues/outcomes,

evident by changes in activation of reward-related networks during

reward trials.

References

1. Knutson B, Westdorp A, Kaiser E, Hommer D (2000) FMRI

visualization of brain activity during a monetary incentive delay

task. Neuroimage 12(1):20–27

2. Galvan A, Hare TA, Parra CE, Penn J, Voss H, Glover G, Casey

BJ (2006) Earlier development of the accumbens relative to

orbitofrontal cortex might underlie risk-taking behavior in

adolescents. J Neurosci 26(25):6885–6892

3. Gatzke-Kopp LM, Beauchaine TP, Shannon KE, Chipman J,

Fleming AP, Crowell SE, Liang O, Johnson LC, Aylward E

(2009) Neurological correlates of reward responding in adoles-

cents with and without externalizing behavior disorders. J

Abnorm Psychol 118(1):203–213

Consistently inconsistent: effects of reward on patterns

of intraindividual variability

Sarah L. Karalunas1, Cynthia Huang-Pollock1

1The Pennsylvania State University, Pennsylvania, USA

Intra-individual variability in reaction times (IVR) has largely been

ignored as ‘‘noise’’ within data of interest when looking at cognitive

deficits associated ADHD. However, greater than expected IVR is now

recognized as one of the most prominent features of the disorder, with

particular emphasis on low-frequency patterns of IRV. Currently, it

remains unclear whether IRV in general, or specific IRV frequency

patterns, are a stable feature of cognitive processing or whether reward

modulates them. Fourier transform analyses were applied to RT time-

series from a go/no-go task with reward ($0.05/correct response) and

non-reward blocks. Preliminary data from the current study

(NADHD = 7) indicate that school-age children (xage = 9.5 years) with

ADHD show more low-frequency IRV in non-reward than reward blocks

(p = 0.09). High-frequency IRV is stable across reward and non-reward

blocks p = 0.38). Results from the full sample (NADHD = 25, NCon-

trol = 25) will be discussed in terms of stability of low-frequency IRV

across contexts, with particular emphasis on whether reward allows

children with ADHD to correct (i.e. reduce low-frequency IRV specifi-

cally) or merely compensate for (i.e. reduce IRV overall but not

specifically low-frequency IRV) initial deficits.

Keywords: ADHD, Intra-individual variability, Motivation, Reward,

Cognitive processing


123

Reward and methylphenidate modulate task-related

default mode network deactivation in ADHD

Elizabeth B. Liddle1, Chris Hollis1, Martin J. Batty1,Madeleine J. Groom1, John J. Totman2, Mario Liotti3, Gaia Scerif4,Peter F. Liddle1.

1University of Nottingham, Nottingham, UK; 2King’s College,

London, UK; 3Simon Fraser University, Burnaby, Canada;4University of Oxford, Oxford, UK

Introduction and objective: Lapses of attention-to-task are associ-

ated with intrusive default mode network (DMN) activity [1], a

distributed brain system normally deactivated during tasks requiring

attention to the external world [2]. Given the alleviation of attentional

impairments of ADHD by task engagement [3], we hypothesised that

performance-based rewards during an inhibitory control task would

enhance task-related DMN deactivation in ADHD, and that methyl-

phenidate, an indirect dopamine agonist, might lower the reward

threshold for DMN deactivation.

Methods: fMRI images were obtained from eighteen methylpheni-

date-responsive children with ADHD and 18 pairwise-matched

typically developing children aged 9–15 years, during a paced go/no-

go task. Motivational incentive and the medication status of the

ADHD children were manipulated.

Results: Both groups performed significantly better in the high-

incentive condition. However, unlike typically developing children,

children with ADHD, off-methylphenidate showed attenuated task-

related DMN deactivation in the low-incentive condition, an effect

abolished by methylphenidate.

Discussion: Reduced motivational salience of task-relevant stimuli

results in attenuated DMN deactivation in ADHD, and may reflect

intrusive DMN activity.

Conclusion: A raised reward threshold for task-related DMN deac-

tivation in ADHD is normalised by an indirect dopamine agonist.

References

1. Sonuga-Barke EJS, Castellanos FX (2007) Spontaneous atten-

tional fluctuations in impaired states and pathological conditions:

a neurobiological hypothesis. Neurosci Biobehav Rev 31:977–

986

2. Raichle ME et al (2001) A default mode of brain function. Proc

Natl Acad Sci USA 98:676–682

3. Sagvolden T, Sergeant JA (1998) Attention deficit/hyperactivity

disorder - from brain dysfunctions to behaviour. Behav Brain Res

94:1–10

Testing hypotheses of altered reinforcement sensitivity

in ADHD: a research agenda

Marjolein Luman1, Gail Tripp2, Anouk Scheres3,4

1Department of Clinical Neuropsychology, Vrije Universiteit

Amsterdam, Amsterdam, The Netherlands; 2Okinawa Institute of

Science and Technology, Okinawa, Japan; 3Department of

Psychology, University of Arizona, Tucson, USA; 4Behavioural

Science Institute, Radboud University Nijmegen, Nijmegen, The

Netherlands

Introduction and objective: ADHD is associated with altered rein-

forcement sensitivity, despite a number of inconsistent findings. To

date, one of the issues here is a gap between experimental findings

and theoretical models. To solve this gap, seven current models on

reinforcement sensitivity in ADHD and their predictions are

compared.

Methods: Fifteen predictions that are derived from the seven models

are presented and compared to experimental evidence.

Results: It becomes clear that many studies have focused on behav-

ioral changes in the face of reward and response cost over non-

reward, and on delay discounting. These are behavioral phenomena

that are predicted by most models. It is argued that in order to dis-

criminate between the models, there is a need to test some of the more

‘unique’ predictions. Additionally, there is a lack in studies that test

predictions regarding the underlying cognitive or neural mechanisms

of altered reinforcement sensitivity in ADHD.

Discussion and conclusion: It is believed that the 15 theoretically-

driven predictions could serve as a useful guide to the systematic

evaluation of altered reinforcement sensitivity in ADHD.

An investigation of DAT110/6 and COMTVal158Met effects

on reward-circuit responsiveness and impulsivity

in male adolescents with attention-deficit/hyperactivity

disorder combined subtype and controls

Y. Paloyelis1, M.A. Mehta2, S.V. Faraone3, P. Asherson1, J. Kuntsi1

1MRC SDGP Centre, Institute of Psychiatry, King’s College, London,

UK; 2Centre for Neuroimaging Sciences, Institute of Psychiatry,

King’s College, London, UK; 3Departments of Psychiatry and of

Neuroscience and Physiology, SUNY Upstate Medical University,

Syracuse, NY, USA

Introduction: Existing evidence links deficiencies in dopamine sig-

naling and abnormalities in dopamine-modulated fronto-striatal

circuits with ADHD and reward-related impulsivity, one of its key

characteristics [1, 2]. Yet relatively little research has investigated the

functional significance of variation in genes regulating dopamine

catabolism in fronto-striatal brain regions. Previously, we showed that

reward-related impulsivity can be predicted by DAT110/6 haplotype

dosage and the COMTVal158Met genotype in ADHD-CT and controls

[3].

Aim/objectives: We aim to understand the functional significance of

the DAT110/6 haplotype, which has been associated with ADHD in

children and adolescents, and of COMTVal158Met, with respect to brain

function during reward anticipation/loss avoidance and outcome

presentation, which provides one possible mechanism through which

dopamine gene variation may be linked to behavioural impulsivity, a

key characteristic of ADHD.

Method: We measured behavioural impulsivity and collected fMRI

data during reward anticipation/loss avoidance and outcome presen-

tation from a sample of 30 boys with ADHD-CT and 30 age-matched

controls, selected on the basis of the DAT110/6 haplotype and geno-

typed for COMTVal158Met. Data are currently under analysis and

findings will be presented at the meeting.

References

1. Paloyelis Y, Asherson P, Kuntsi J (2009) Are ADHD symptoms

associated with delay aversion or choice impulsivity? A general

population study. J Am Acad Child Adolesc Psychiatry

48(8):837–846

2. Luman M, Tripp G, Scheres A (2010) Identifying the neurobi-

ology of altered reinforcement sensitivity in ADHD: a review and

research agenda. Neurosci Biobehav Rev 34(5):744–754

3. Paloyelis Y, Asherson P, Mehta MA, Faraone SV, Kuntsi J

(2010) DAT1 and COMT effects on delay discounting and trait

impulsivity in male adolescents with attention deficit/hyperac-

tivity disorder and healthy controls (in review)


123

Measuring inhibitory control in motivational contexts

in ADHD

Anouk Scheres1

1Behavioural Science Institute, Radboud University Nijmegen,


Single causal pathway models of attention-deficit/hyperactivity dis-

order (ADHD) have emphasized deficits in executive function,

primarily inhibitory control. However, accumulating evidence of

considerable inter-individual differences in executive function deficits

in this disorder challenges this view—our current understanding of

the heterogeneous nature of ADHD has caused a shift towards iden-

tifying multiple causal pathways. Although recent theoretical models

have prompted ADHD researchers to study motivational processes in

addition to executive functions, there is a relative lack of research that

examines the conjunction of these two important pathways. Here, I

will present an original approach to study the interaction between

motivation and executive function in ADHD, specifically bottom-up

effects of motivation on inhibitory control. Bottom-up effects of

motivation are defined here as disruptions of motivational states on

inhibitory control. We hypothesize that more variance in ADHD

symptoms can be explained by performance on motivational inhibi-

tion tasks than inhibition tasks with no motivational contexts. Task

designs will be presented and preliminary data in healthy groups and

groups with ADHD will be discussed.

Reinforcement-related behaviour in monetary incentive

tasks: different fMRI approaches to investigate brain

reward circuitry

Sabina Steiner1, Frauke Nees2, Sabine Vollstadt-Klein3, Karl Mann3,Herta Flor2, Marcella Rietschel4, Gunter Schumann5,Tobias Banaschewski1, Luise Poustka1

1Klinik fur Psychiatrie und Psychotherapie des Kindes- und

Jugendalters, ZI, Mannheim, Germany; 2Abteilung fur

Neuropsychologie und Klinische Psychologie, Ruprechts-Karls-

Universitat Heidelberg, ZI, Mannheim, Germany; 3Klinik fur

Abhangiges Verhalten und Suchtmedizin, ZI, Mannheim, Germany;4Abteilung fur Genetische Epidemiologie in der Psychiatrie, ZI,

Mannheim, Germany; 5Interdisciplinary Research Group Addiction

MRC-SGDP Centre, Institute of Psychiatry at King’s College,

London, UK

Introduction: Functional neuroimaging of the brain reward system

revealed several neural networks involved in reward processing. Still,

the specificity of neural responses to reward stimuli or their magni-

tude remains still unclear.

Method: Using a reward-fMRI paradigm (MID task [1]) on a sample

of 150 healthy adolescents aged 13–14 years, we aimed at identifying

how different reward magnitudes activate mesolimbic brain structures

during the anticipation phase, with specific focus on gender differ-

ences. The study is part of a large European multicentre study

(IMAGEN), designed to identify the impact of brain function on

reinforcement-sensitivity in healthy adolescents.

Results: Different activation patterns were found in mesolimbic brain

structures depending on the magnitude of the reward. While this

effect was present in both boys and girls, only boys showed additional

activation in the ACC and insula.

Discussion: Like in study 1a, we found ventral striatal brain activa-

tion during reward processing for anticipation of win. Expected

reward size had significant effect on reward related brain structures,

with motivational differences in boys compared to girls.

Conclusions: Activation of reward related brain structures seem to be

age-independent, except for the NAcc, were we found preliminary

evidence for decreased activation in adolescents.

Reference

1. Knutson B et al (2001) Anticipation of increasing monetary

reward selectivity recruits nucleus accumbens. J Neurosci 21:1–5

Two different reward paradigms: a comparison

of the results in 14-year-old healthy adolescents

Sabina Steiner1*, Frauke Nees2*, Sabine Vollstadt-Klein3,Luise Poustka1, Marcella Rietschel4, Karl Mann3, Gunter Schumann5,Tobias Banaschewski1, Herta Flor2


Central Institute of Mental Health, Mannheim, Germany;2Department of Cognitive and Clinical Neuroscience, Central

Institute of Mental Health, University of Heidelberg, Mannheim,

Germany; 3Department of Addictive Behaviour and Addiction

Medicine, Central Institute of Mental Health, Mannheim, Germany;4Department of Genetic Epidemiology in Psychiatry, Central Institute

of Mental Health, Mannheim, Germany; 5Interdisciplinary Research

Group, Department of Addiction Biology, Addiction MRC-SGDP

Centre, Institute of Psychiatry at King’s College, London, UK

*Joint first authors

Introduction and objective: To identify brain regions involved in the

processing of monetary reward versus a simple guessing task, two

different paradigms were compared.

Method: During fMRI, 40 healthy adolescents completed a guessing

task. In each trial, the backsides of two playing cards were presented;

subjects were asked to guess the card with the red king. In addition,

subjects completed a monetary incentive delay (MID) task.

Results: Analyses focused on changes in blood oxygen level depen-

dent (BOLD) contrasts during reward (MID) and during reward and

punishment processing (guessing task) in both anticipation and

feedback phases. Preliminary results showed a clear differentiation in

reward-related brain regions such as the striatum in response to

reward magnitudes (high vs. low win) in the MID task only.

Conclusion/discussion: Our findings suggest MID task to be more

adequate in assessing reward processing in adolescence compared to a

simple guessing task, at least in respect to the differentiation of

reward magnitudes.

IMAGEN receives research funding from the European Community’s

Sixth Framework Program (LSHM-CT-2007-037286).

References

1. Yacubian J, Glascher J, Schroeder K, Sommer T, Braus DF,

Buchel C (2006) Dissociable systems for gain- and loss-related

value predictions and errors of prediction in the human brain. J

Neurosci 26(37):9530–9537

2. Knutson B, Westdorp A, Kaiser E, HommerD (2000) FMRI

visualization of brain activity during a monetary incentive delay

task. Neuroimage 12:20–27

3. Knutson B, Fong GW, Adams CM, Varner JL, Hommer D (2001)

Dissociation of reward anticipation and outcome with event-

related fMRI. Neuroreport 12:3683–3687


123

Neural substrates underlying reward anticipation

and evaluation in children with ADHD

Catharina S. van Meel1,2

1Institute for Psychology, Erasmus University, Rotterdam, The

Netherlands; 2Leiden University Institute for Psychological Research,

Leiden University, Leiden, The Netherlands

Introduction and objective: Several neurobiological models of

ADHD propose that a disturbance in the meso-limbic branch of the

midbrain dopamine system causes abnormal response to reinforce-

ment. The present study investigated ERPs related to the anticipation

and evaluation of financial rewards and penalties in children with

ADHD and controls during guessing.

Methods: During a passive slot-machine task, children watched three

pictures appearing successively on a screen. Picture sequences

included either three different pictures, two identical and one different

picture, or three identical pictures. Depending on the condition, par-

ticipants were told that they would either gain or lose money

whenever all pictures were identical.

Results: When anticipating outcomes, children with ADHD failed to

adjust their levels of attention to the chance of obtaining rewards or

penalties, as indicated by shallow stimulus-preceding negativities.

Reduced feedback negativity and P300 suggest that both the rapid

detection of omitted rewards and omitted penalties and more elabo-

rate cognitive–affective evaluation is abnormal.

Discussion and conclusion: Children with ADHD may be controlled

by immediate prospects rather than longer-term goals due to a lack of

motivational guidance.

Keywords: ERP, Feedback processing, Reinforcement, Reward,

Punishment

References

1. Nigg JT, Casey BJ (2005) An integrative theory of attention-

deficit/hyperactivity disorder based on the cognitive and affective

neurosciences. Dev Psychopathol 17:785–806

2. Sagvolden T, Johansen EB, Aase H, Russell VA (2005) A

dynamic developmental theory of attention-deficit/hyperactivity

disorder (ADHD) predominantly hyperactive/impulsive and

combined subtypes. Behav Brain Sci 28:397–419

3. Tripp G, Wickens J (2008) Research review: dopamine transfer

deficit: a neurobiological theory of altered reinforcement mech-

anisms in ADHD. J Child Psychol Psychiatry 49:691–704

Neural correlates of valence, salience and feedback-

delay in a monetary incentive task: finding the best

fMRI approach to investigate brain reward circuitry.

Isabella Wolf1, Karina Kochendorfer1, Traute Demirakca2,Matthias Ruf2, Martin Holtmann3, Daniel Brandeis1,Tobias Banaschewski1


CIMH, Mannheim, Germany; 2Department Neuroimaging, CIMH,

Mannheim, Germany; 3LWL-Hospital for Child and Adolescent

Psychiatry, Ruhr-University Bochum, Bochum, Germany

Introduction: We compared effects of valence, salience and delayed

feedback on reward associated brain areas of 30 young healthy stu-

dents (20–30 years). The aim of the study was to evaluate three fMRI

paradigms to find out which one activates the ventral striatum most

strongly, and thus represents the best candidate for a later study on

altered reward processing in patients.

Methods: FMRI data from 30 participants (healthy young adults) was

acquired in a 3T MRI Siemens scanner to quantify brain activation in

the reward system in all three event-related tasks.

Results: In the reward system, activation was higher in reward than in

neutral conditions. Anticipation of reward led to higher ventral stri-

atum activation than anticipation of avoiding loss (valence), and the

expected reward size had significant effect on reward related activa-

tion (salience). Delayed feedback revealed no significant brain

activity in reward system.

Conclusions: The study identified optimal conditions for the second,

clinical phase of our study. We will investigate the reward system of

ADHD patients using the best fMRI-paradigm combining positive

valence and high salience.

Poster Sessions E: NeuropsychologicalIssues

A continuous attention tracking task

for the comprehensive assessment of attention processes

in ADHD and non-ADHD subjects

Lourdes Anllo-Vento1,2, Benjamin N. Cipollini3,Vladimir Lopez-Hernandez4, David L. Woods5

1Department of Psychology, University of Granada, Granada, Spain;2F. Oloriz Institute of Neurosciences, University of Granada,

Granada, Spain; 3Department of Cognitive Sciences, University of

California, San Diego, USA; 4Department of Psychology, Catholic

University of Chile, Santiago, Chile; 5Department of Neurology,

University of California at Davis, USA

Introduction and objectives: Despite the usefulness of CPTs [1] in

the assessment of attention impairments, current computer-based CPT

versions are limited in their ability to detect and profile the multiple

cognitive operations that constitute attention. Here, we present a

continuous attention tracking task with 30+ measures of attention in a

3D video-game environment with sub-second temporal resolution.

Methods: Twelve ADHD and 12 non-ADHD adults participated. EEG

was recorded while subjects engaged in the game for 20 min. We

recorded event-related potentials and responses to targets and non-tar-

gets, tracking accuracy, and latency of stop-signal responses at 60 Hz.

Results: Overall tracking accuracy was comparable for ADHD and

non-ADHD subjects, but inhibition of tracking during a stop-signal was

greater in the non-ADHD group. Similarly, non-ADHD subjects stop-

ped tracking faster, and responded to targets faster and more accurately

than ADHD subjects. ERPs evoked by target and non-target signals

showed that only the brain activity of non-ADHD subjects appeared to

be selectively modulated starting at 180 ms post-stimulus onset.

Discussion and conclusions: This video-game replicates and extends

prior CPT [2] and stop-signal task [2, 3] findings in an ecologically

valid and clinically useful setup.

References

1. Rosvold HE, Mirsky AF et al (1956) A continuous performance

test of brain damage. J Consult Psychol 20:343–350

2. Pollak Y, Weiss PL, Rizzo AA, Weizer M, Shriki L, Shalev RS,

Gross-Tsur V (2009) The utility of a continuous performance test

embedded in virtual reality in measuring ADHD-related deficits.

J Dev Behav Pediatr 30:2–6

3. Soreni N, Crosbie J, Ickowicz A, Schachar R (2009) Stop signal

and Conners’ continuous performance tasks: test–retest reliability

of two inhibition measures in ADHD children. J Atten Disord

13:137–143


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Effects of auditory spatial attention on behavioral

performance and intra-subject variability in ADHD

and non-ADHD adults

L. Anllo-Vento1,2, V. Lopez-Hernandez3, B.N.Cipollini4,W.A. Teder-Salejarvi5, S.A. Hillyard6

1Department of Psychology, University of Granada, Granada, Spain;2F. Oloriz Institute of Neurosciences, University of Granada,

Granada, Spain; 3Department of Psychology, Catholic University of

Chile, Santiago, Chile; 4Department of Cognitive Sciences,

University of California, San Diego, USA; 5Department of

Psychology, North Dakota State University, Fargo, USA,6Department of Neurosciences, University of California, San Diego,

USA

Introduction and objectives: We used a selective listening task [1]

that requires subjects to discriminate between similar sounds coming

from a single, attended location within a multi-speaker array. Objectives

were: (1) to compare ADHD and non-ADHD adults in their ability to

selectively focus on one sound source and ignore irrelevant, competing

sounds; and (2) to examine whether spatial auditory attention affected

intra-subject variability [2] differently in these two groups.

Methods: Participants were 20 ADHD and 20 matched non-ADHD

adults. They discriminated infrequent targets from frequent non-target

sounds at one of two speaker locations (center vs. right), separated by

90�. We calculated rates of hits and false alarms, and their reaction

times, as well as ex-Gaussian parameters [3] measuring average

performance, variability, and extreme responses or attentional lapses.

Results: Non-ADHD subjects had slower RTs at unattended locations

and were generally more accurate than ADHD adults. For both

groups, attention decreased RT averages and reduced intra-subject

variability, but ADHD subjects had more extreme values or lapses of

attention at the attended location than their non-ADHD counterparts.

Discussion and conclusions: ADHD adults are less able than non-

ADHD subjects to focus auditory attention in a noisy environment.

References

1. Teder-Salejarvi WA, Hillyard SA, Roder B, Neville HJ (1999)

Spatial attention to central and peripheral auditory stimuli as

indexed by event-related potentials. Cogn Brain Res 8:213–227

2. Geurts HM, Grasman RPPP, Verte S, Oosterlaan J, Roeyers H,

van Kammen SM, Sergeant JA (2008) Intra-individual variability

in ADHD, autism spectrum disorders and Tourette’s syndrome.

Neuropsychologia 46:3030–3041

3. Van Zandt T (2002) Analysis of response time distributions. In:

Wixted JT (ed) Stevens’ handbook of experimental psychology,

3rd edn, vol 4. Methodology in experimental psychology. Wiley,

New York, pp 461–516

The relationship of motor coordination and ADHD

A.B. Ayaz1, M. Ayaz1, Y. Yazgan2

1Adapazari State Hospital Child Psychiatry Clinic, Adapazari,

Turkey; 2Marmara University Hospital Child Psychiatry Clinic,

Istanbul, Turkey

Introduction and objective: The aim of this study was to investigate

motor performance of children with ADHD in contrast to age- and

gender-matched normal control children.

Method: Sixty-four ADHD subjects ascertained according to DSM-

IV criteria and 69 controls participated. Purdue pegboard test (PPT)

including four subtests; dominant hand (DH), non-dominant hand

(nDH), both hands (BH), and assembly (Ass) were used for assess-

ment of motor coordination of children. ADHD group had

significantly lower IQ scores, so prorating using covariant analysis

was performed.

Results: Children with ADHD had significantly more motor coordi-

nation problems than controls in all subtests. However, after the

prorating of IQ scores, the difference between groups was restricted to

DH and nDH subtests (p = 0.03 and 0.04, respectively). Girls with

ADHD had more motor coordination problems than control girls in

DH, nDH and Ass subtests (p = 0.00, 0.00 and 0.03, respectively).

When the analysis was restricted to the right handed children, there

was significant difference in PPT scores between the ADHD and

control groups.

Discussion: Our results confirm previous findings of an association

between ADHD diagnosis and poor motor performance [1].

Reference

1. Fliers E, Rommelse N, Vermeulen SHHM et al (2008) Motor

coordination problems in children and adolescents with ADHD

rated by parents and teachers: effects of age and gender. J Neural

Transm 115:211–220

Neuropsychological functioning and clinical symptoms

in adult ADHD: a multidimensional analysis

Livia Balogh1, Pal Czobor1,2, Viktoria Simon1, Istvan Bitter1

1Department of Psychiatry and Psychotherapy Semmelweis

University, Budapest, Hungary; 2Nathan Kline Institute for

Psychiatric Research, Orangeburg, NY, USA

Introduction and objective: comparisons of neuropsychological

functioning in adult ADHD and healthy control groups typically yield

only a modest difference, which may result from the insufficiency of

the current categorical DSM-IV classification system. Many

researchers advocate replacing the categorical approach with a

dimensional one, treating the basic underlying symptoms of ADHD as

continua. The objective was to investigate multivariate associations

between ADHD symptoms and neuropsychological variables adopt-

ing a dimensional approach.

Methods: Data were obtained in an epidemiological study of preva-

lence, neuropsychology and genetics of adult ADHD in a sample from

GP practices in Hungary (n = 3,529). Neuropsychological assess-

ments were conducted in positively screened subjects (n = 161).

Associations between symptoms (4 subscales of CAARS [1],

including inattention/memory problems, hyperactivity/restlessness,

impulsivity/emotional lability problem with self-concept) and neu-

ropsychological factors based on variables in the attention, memory,

executive functions and fluency domains were examined via canon-

ical component analysis (CCA).

Results: CCA yielded two significant canonical factors (CF)

[R1 = 0.6 (p = 0.00019) and R2 = 0.5 (p = 0.021), respectively].

Discussion and conclusion: CFs indicated that symptoms of ADHD

and indices of execution functions, memory and fluency, respectively,

are closely related.

Reference

1. Conners CK, Erhardt D, Sparrow EP (1999) Conners’ adult

ADHD rating scales (CAARS). Multi-Health Systems Inc.


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Spelling errors in ADHD children: not just

an attentional issue

Cesare Cornoldi1, Francesco Sella2, Anna M. Re2

1General Psychology Department, University of Padova, Padua, Italy;2Developmental Psychology Department, University of Padova,

Padua, Italy

Many studies have explored the relationship between ADHD and

basic learning skills but very little information is available about the

writing skills of ADHD children. This research examined the per-

formance of children described by their teachers as showing ADHD

symptoms on two writing tasks, a dictation and a copy of texts [2],

compared to a control matched group. ADHD children made more

errors than controls in both the dictation and the copy task. Further-

more, the two groups also showed different patterns of errors. In the

dictation children with ADHD symptoms made more errors with

accents and geminates, supporting previous results [1], and confirm-

ing that this type of error mainly involves sophisticated use of both

phonological and non-phonological indices. In the copy task, they

made a high percentage of phonological errors (absence of correct

correspondence between grapheme and phoneme). This result might

be due to both attentional problems, because, according to the liter-

ature, this of error disappears easily with learning and development.

References

1. Re AM, Pedron M, Cornoldi C (2007) Expressive writing in

children described by their teachers as exhibiting ADHD

symptoms. J Learn Disabil 40:244–255

2. Tressoldi PE, Cornoldi C (1991) Batteria per la valutazione della

scrittura e della competenza ortografica nella scuola dell’obbligo

(BVSCO, Battery for the assessment of writing skills of children

from 7 to 13 years old). Organizzazioni Speciali, Florence, Italy

Fronto-striatal brain dysfunction in adults

with childhood ADHD and persistent hyperactive/

inattentive behaviours during sustained attention

and reward

Ana Cubillo1, Rozmin Halari1, Eric Taylor1, Katya Rubia1

1Department of Child and Adolescent Psychiatry, Institute of

Psychiatry, King’s College, London, UK

Introduction and objective(s): Children with ADHD have fronto-

striatal and temporo-parietal deficits during tasks of attention and

reward [1, 2]. No fMRI study, however, has investigated neurofunc-

tional correlates of sustained attention and the effects of reward on

this function in medication-naıve adults with ADHD.

Methods: fMRI comparison between 11 medication-naıve adults with

childhood ADHD and persistent inattentive/hyperactive behaviours

and 15 age-matched controls during an event-related rewarded con-

tinuous performance task.

Results: During sustained attention trials, adults with childhood

ADHD showed decreased activation in inferior prefrontal, cingulate,

striatal, and temporal regions, but increased activation in cerebellum,

precuneus, and occipito-parietal regions. During rewarded compared

to non-rewarded trials, patients showed reduced ventromedial pre-

frontal and caudate activation.

Discussion: The findings demonstrate that adults with ADHD who

persist in their symptoms from childhood ADHD show task-relevant

lateral and ventromedial fronto-striatal dysfunctions compared to

healthy controls during attention and reward, respectively. Further-

more, during sustained attention, adults with ADHD seemed to

compensate with alternative occipital-cerebellar activation, leading to

comparable task performance.

Conclusions: Adults with ADHD have impairments in both ‘‘cool’’

and ‘‘hot’’ lateral and ventromedial fronto-striatal networks.

References

1. Rubia K, Smith A, Halari R, Matukura F, Mohammad M, Taylor

E, Brammer M (2009) Disorder-specific dissociation of orbito-

frontal dysfunction in boys with pure Conduct disorder during

reward and ventrolateral prefrontal dysfunction in boys with pure

attention-deficit/hyperactivity disorder during sustained attention.

Am J Psychiatry 166:83–94

2. Rubia K, Halari R, Cubillo A, Mohammad M, Taylor E (2009)

Methylphenidate normalises activation and functional connectiv-

ity deficits in attention and motivation networks in medication-

naıve children with ADHD during a rewarded continuous

performance task. Neuropharmacology 57(7–8):640–652

Neuropsychological differences among subtypes

of adult ADHD

Pal Czobor1,2, Viktoria Simon1, Livia Balogh1, Istvan Bitter1

1Department of Psychiatry and Psychotherapy, Semmelweis

University, Budapest, Hungary; 2Nathan Kline Institute for

Psychiatric Research, Orangeburg, NY, USA

Introduction and objective: The few studies that investigated neu-

ropsychological differences among subtypes of adult ADHD yielded

inconsistent results, which may be due to the heterogeneity in

underlying clinical symptom presentation over the course of illness.

Our objective was to delineate differences in neuropsychological

profiles among developmentally stable ADHD subtypes.

Methods: Data were collected in an epidemiological study examining

the prevalence, neuropsychology and genetics of adult ADHD in

Hungary using a sample from GP practices (n = 3,529). Neuropsy-

chological assessments focused on positively screened subjects

(n = 161), examining attention, memory, executive functions and

fluency. Subjects were classified into groups with developmentally

stable presentation of inattentive, hyperactive and combined subtypes,

respectively, if their subtype classification showed no change from

childhood to adulthood. Stable subtypes were compared with each

other and with subjects with subthreshold symptom presentation.

Results: Significant (p \ 0.05) differences were found between the

stable subtypes and the ‘‘subthreshold symptom’’ group in memory,

executive functions and fluency.

Discussion and conclusion: The combined and inattentive subtypes

display the worst performance in tests of memory, and the inattentive

and hyperactive groups display more deficits in executive functioning.

ADHD preschoolers and visuospatial working memory

Valentina De Franchis1, Cesare Cornoldi2

1University of Genova, Genova, Italy; 2University of Padova, Padua,

Italy

Introduction and objective: Some studies report deficits in WM [2]

whereas others report no association between WM and preschool

ADHD symptoms [1]. The aim of this study was to examine the


123

hypothesis that a working memory deficit is also found in children

with attention deficit/hyperactivity disorder (ADHD) symptoms as

young as 5 years and is related to the control of interfering

information.

Methods: One group of 23 kindergarten children identified by the

presence of ADHD symptoms and one group of 23 children matched

for gender, age, and socioeconomic status were administered a vis-

uospatial working memory task, the dual request selective task

(DSRT), that required the selective recall of information.

Results: A 2 9 2 ANOVA (error types 9 groups) on the corrected

scores showed that children with ADHD symptoms performed more

poorly than controls and were affected to a particularly high extent by

intrusion errors.

Discussion: The study provides further evidence for the observation

that children with ADHD symptoms present difficulties in WM tasks

and demonstrates that this also applies at the early age of 5 years.

Conclusion: The study suggests that WM control may be an early

neuropsychological index of ADHD problems.

References

1. Sonuga-Barke EJS, Dalen L, Daley D, Remington B (2002) Are

planning, working memory, and inhibition associated with

individual differences in preschool ADHD symptoms? Dev

Neuropsychol 21(3):255–272

2. Thorell LB, Wahlstedt C (2006) Executive functioning deficits in

relation to symptoms of ADHD and/ or ODD in preschool

children. Infant Child Dev 15:503–518

Executive function and school achievement in children

at risk of ADHD: a longitudinal study

Valentina De Franchis1, Laura Traverso1, M. Carmen Usai1,Paola Viterbori1

1University of Genoa, Genoa, Italy

Introduction and objective: ADHD children appear to be charac-

terized by an executive dysfunction [2]; ADHD symptoms have been

associated with poor school achievements [1]. The goals were to

examine the development of executive functions (EF) in children at

risk of ADHD from preschool to school entry and the relationship

between ADHD symptoms in the last year of kindergarten and school

achievements 1 year later.

Methods: Fifty-seven children in the last year of kindergarten were

divided into two groups on the basis of scores from a teachers’ rating

scale (SDAI) for ADHD symptoms. Children have been evaluated

individually on a comprehensive battery of seven tests assessing EF at

5 and 6 years old and on a battery assessing academic achievements.

Results: We compared performance of two groups in the last year of

kindergarten and again in the first year of primary school with Mann-

Whitney test.

Discussion: Children with ADHD risk showed significantly poorer

performance than controls in some EF tasks and in some academic

achievements, in particular writing under dictation.

Conclusion: Some EF measures assessed both in preschool and in

primary school were found to be associated with the risk of ADHD.

This condition of weakness regarding the EF involves also the aca-

demic achievements.

References

1. Barry TD, Lyman RD, Klinger LG (2002) Academic under-

achievement and attention-deficit/hyperactivity disorder: the

negative impact of symptom severity on school performance. J

Sch Psychol 40:259–283

2. Castellanos FX, Sonuga-Barke EJS, Milham MP, Tannock R

(2006) Characterizing cognition in ADHD: beyond executive

dysfunction. Trends Cogn Sci 10:117–123

ADHD symptoms, EF deficits, academic performance

and social functioning in children

Sara Folke1, Ann-Margret Rydell1

1Department of Psychology, Uppsala University, Uppsala, Sweden

ADHD symptoms and deficits in executive function (EF) are often

related, EF deficits seen as an underlying factor in the expression of

ADHD symptoms. Both of these phenomena in turn relate to poor

social functioning and poor academic performance, however the

joint effects of ADHD symptoms and EF deficits need further

investigation [1, 2]. This study examined the independent and

interactive effects of ADHD symptoms and EF deficits on social

functioning and academic performance. Eighty-six 10-year-olds

(57% girls) with a wide variation in ADHD symptoms participated.

ADHD-symptom ratings and social-functioning ratings were based

on parent and teacher reports. Children completed EF tests and

reported on peer relations. ADHD symptoms and EF deficits gave

independent contributions to academic performance, but only

ADHD symptoms contributed independently to social functioning.

There were no interaction effects. ADHD symptoms and EF deficits

related to a positive bias [3] regarding peer relations. ADHD

symptoms and EF deficits directly relate to school performance,

however, the effect of EF deficits on social functioning is mostly via

behavioral symptoms.

References

1. Biederman J, Monuteaux MC, Doyle AE, Seidman LJ, Wilens

TE, Ferrero F, Morgan CL et al (2004) Impact of executive

function deficits and attention-deficit/hyperactivity disorder

(ADHD) on academic outcomes in children. J Consult Clin

Psychol 72(5):10

2. Diamantopoulou S, Rydell AM, Thorell LB, Bohlin G (2007)

Impact of executive functioning and symptoms of attention

deficit hyperactivity disorder on children’s peer relations and

school performance. Dev Neuropsychol 32(1):521–542

3. Hoza B, Gerdes AC, Hinshaw SP, Arnold LE, Pelham WE Jr,

Molina BS, Abikoff HB et al (2004). Self-perceptions of

competence in children with ADHD and comparison children.

JJ Consult Clin Psychol 72:382–391

Time perception, executive function and phonological

skills in children with attention deficit hyperactivity

disorder (ADHD) and reading disorder (RD)

Debbie Gooch1, Maggie Snowling1, Charles Hulme1

1The University of York, York, UK

Introduction and objectives: This study aimed to determine whether

deficits in time perception are associated with ADHD and/or RD or

whether they are unique to children with comorbid ADHD + RD.

Methods: A 2 (ADHD yes/no) 9 2 (RD yes/no) factorial design

yielded four groups of children (17 with ADHD-only, 17 with RD-

only, 25 with comorbid ADHD + RD and 42 typically developing

controls) who were matched for age and non-verbal ability. The


123

children completed measures of phonological skills, executive func-

tion and time perception.

Results: The RD was associated with impairments in phonological

skills and duration discrimination (though deficits in duration dis-

crimination appeared to be attributable to symptoms of inattention in

this group). ADHD was associated with impairments in time per-

ception and executive function. Children with ADHD + RD showed

an additive combination of the deficits associated with ADHD-only

and RD-only.

Discussion: Findings are discussed in relation to theories of ADHD

and RD and current explanations of comorbidity are considered.

Conclusions: ADHD and RD appear to be separate disorders asso-

ciated with distinct patterns of cognitive deficit, which are present in

combination in the comorbid disorder.

Attention skills and executive function in pre-school

children at risk of dyslexia

Debbie Gooch1, Hannah Nash1, Maggie Snowling1, Charles Hulme1

1University of York, York, UK

Introduction and objective: This study aims to address the question

of whether there are signs of comorbid difficulties in attention and/or

hyperactivity/impulsivity in children at risk of dyslexia.

Methods: Two-hundred two children [79 at family risk for dyslexia

(FR), 41 language impaired (LI) and 81 typically developing (TD)],

aged 3–4 years, completed measures of complex inhibition, selective

attention, sustained attention, reaction time and memory.

Results: There was a clear step pattern of performance on measures

of inhibition and attention at T1 (TD [ FR [ LI); LI children

remained weak compared to TD controls at T2. A clear step pattern

on measures of sustained attention, reaction time and memory

(TD [ FR [ LI) was found at T2. Moderate correlations between

children’s language skills and their performance on measures of

executive function and attention were found.

Discussion: Results are discussed in relation to theories of ADHD.

Explanations of the comorbidity between ADHD and dyslexia are

considered.

Conclusions: Pre-school children at risk of dyslexia had weaknesses

in skills known to be impaired in ADHD. However, it is important to

consider the impact that language skills may have on children’s

performance.

The impact of ADHD on neuropsychological

development in early adolescence: a longitudinal

case–control study

D. Hayward1; S.M. Rhodes2; C. Grimmer1; K. Matthews3;D.R. Coghill3

1NHS Tayside, Dundee, Scotland, UK; 2Department of Psychology,

University of Strathclyde, Glasgow, Scotland, UK; 3Department of

Psychiatry, University of Dundee, Dundee, Scotland

Introduction and objective: there is little consensus on how neuro-

psychological impairments in ADHD change as individuals mature so

we conducted a longitudinal study of the development of neuropsy-

chological function (NF) from middle childhood to late adolescence.

Methods: Seventy boys with ADHD and 70 matched typically

developing boys (TYP) performed eight CANTAB tasks at Time 1 [1]

(mean age 10.08 years). 17 representative boys from each group were

re-tested 4.5 years later (Time 2). ADHD boys on medication had a 3-

day washout period. Data was analysed using repeated measures

ANCOVA.

Results: The NF improved in both groups on all but two tasks. TYP

boys maintained superior performance on three tasks. The perfor-

mance of ADHD boys caught up with TYP boys on two tasks.

Discussion: In ADHD, some aspects of NF are not affected, some

deficits disappear with maturity and some deficits persist.

Conclusion: There appears to be differences in the developmental

trajectories of discrete aspects of NF in those with and without

ADHD. These differences presumably reflect differences in brain

maturation but neuropsychological development in ADHD is not

exclusively delayed or abnormal [2].

References

1. Rhodes SM, Coghill DR, Matthews K (2005) Neuropsycholog-

ical functioning in stimulant-naive boys with hyperkinetic

disorder. Psychol Med 35(8):1109–1120

2. Shaw P, Eckstrand K, Sharp W, Blumenthal J, Lerch JP,

Greenstein D, Clasen L, Evans A, Giedd J, Rapoport JL (2007)

Attention-deficit/hyperactivity disorder is characterized by a

delay in cortical maturation. Proc Natl Acad Sci USA

104(49):19649–19654

Right-sided spatial difficulties in ADHD demonstrated

in continuous movement control

K.A. Johnson1,2, A. Daibhis1, C.T. Tobin1, R. Acheson1, A. Watchorn1,A. Mulligan3, E. Barry3, J.L. Bradshaw4, M. Gill3, I.H. Robertson1

1School of Psychology and Trinity College Institute of Neuroscience,

Trinity College Dublin, Dublin 2, Ireland; 2School of Psychology,

Queen’s University Belfast, Belfast BT7 1NN, Northern Ireland;3School of Medicine and Health Sciences and Trinity College

Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland;4School of Psychology, Psychiatry and Psychological Medicine,

Monash University, Clayton 3800, VIC, Australia

Introduction and objective: Children with ADHD often show spatial

attentional deficits, exhibiting a subtle rightwards bias. Approxi-

mately 50% of children with ADHD also show signs of movement

dysfunction. The nature of this movement dysfunction and possible

interactions with spatial attention difficulties has not been clearly

described.

Methods: Thirty-one children with and 31 without ADHD performed

a target-joining movement kinematic task. Constant error in the X and

Y planes, peak absolute velocity and acceleration, movement time,

the number of pauses and pause time were analysed.

Results: Children with ADHD were less accurate in the X plane when

moving towards the right-sided targets over the long distance. Greater

variability in target accuracy was shown when moving towards the

small target on the right side.

Discussion: Apart from a significantly increased rate of acceleration

across all conditions, the children with ADHD demonstrated no

temporal difficulties with the task; rather they showed subtle right-

sided spatial difficulties.

Conclusion: These results suggest that the subtle spatial bias towards

the right that has been demonstrated in ADHD in spatial attention also

extends into the continuous movement domain.

Reference

1. Johnson KA, Daibhis A, Tobin C, Acheson R, Watchorn A,

Mulligan A, Barry E, Bradshaw JL, Gill M, Robertson IH (2010)

Right-sided spatial difficulties in ADHD demonstrated in


123

continuous movement control. Neuropsychologia 48(5):1255–

1264

Why is ADHD so frequently associated with specific

language impairment?

Solveig Jonsdottir1,2

1Department of Neurology, Landspitali University Hospital,

Reykjavık, Iceland; 2Department of Medicine, University of Iceland,

Reykjavık, Iceland

Introduction and objective: Specific language impairment (SLI) is

frequently comorbid with ADHD and other neurodevelopmental

disorders, but the reason is not known. Phonemic verbal fluency is

believed to rely on prefrontal structures while semantic verbal fluency

is mediated by temporal structures. The objective of the study was to

examine the relationship between language ability and phonemic and

semantic verbal fluency in children with ADHD and other neurode-

velopmental disorders.

Methods: Participants were 68 children aged 8–12 years who were

referred to a tertiary ADHD clinic. Tests of language development,

phonemic and semantic verbal fluency, and nonverbal intelligence

were administered.

Results: The results show that language ability of the children was

significantly related to phonemic verbal fluency (p = 0.003), but no

relationship was found with semantic verbal fluency (p = 0.434).

Discussion: The findings of the study indicate that impaired language

ability may be related to prefrontal dysfunction which might help

explain why SLI so frequently co-occurs with ADHD and other

neurodevelopmental disorders.

Conclusion: It is concluded that the results of the study support the

procedural deficit hypothesis (PDH) which proposes that SLI is

caused by abnormalities of the frontostriatal network.

Reference

1. Ullman MT, Pierpont EI (2005) Specific language impairment is

not specific to language: the procedural deficit hypothesis. Cortex

41:399–433

Motor and balance deficits in ADHD: kinetic and EMG

data

Libbe Kooistra1,2, Barbara Ramage1, Susan Crawford2,Marja Cantell1,2

1Department of Pediatrics, University of Calgary, Calgary, AB,

Canada; 2Behavioural Research Unit, Alberta Children’s Hospital,

Calgary, AB, Canada

Introduction and objectives: Whether the high prevalence of motor

impairment in ADHD is attributable to specific underlying neuro-

motor processes is unknown. Some studies suggest that fine motor

performance in ADHD is characterized by timing, coordination, and

force deficits: signals of cerebellar dysfunction. Cerebellar integrity is

key to maintain postural stability. The present study examined bal-

ance features typically affected by cerebellar impairment.

Method: Psychodiagnostic data included the MABC and the COMPS.

Experimental data included force plate and EMG data collected

during static balance and balance perturbation. 47 children with

ADHD (9.3 years) and 39 controls (9.1 years) participated.

Results: The ADHD group performed worse than controls on the

MABC and the COMPS, and showed substantial postural sway during

static balance. Balance perturbation was characterized by early onset

latencies of the tibialis anterior muscles and increased amplitudes of

the gastrocnemius muscles.

Conclusion: Rather than suggesting a motor timing problem, the

early tibialis anterior latencies in children with ADHD suggest a

strategic adjustment secondary to their key deficit: the inability to

generate appropriate muscle force to counter destabilization sug-

gesting medial cerebellar involvement.

References

1. Pitcher TM, Piek JP, Barrett NC (2002) Timing and force control

in boys with attention deficit hyperactivity disorder: subtype

differences and the effect of comorbid developmental coordina-

tion disorder. Hum Mov Sci 21:919–945

2. Timmann D, Horak FB (1998) Perturbed step initiation in

cerebellar subjects. 1. Modifications of postural responses. Exp

Brain Res 119(1):73–84

Validating neuropsychological subtypes of ADHD:

how do children with and without an executive function

deficit differ?

Rikke Lambek1, Rosemary Tannock1, Soeren Dalsgaard1,Anegen Trillingsgaard1, Dorte Damm1, Per Hove Thomsen1

1University of Aarhus, Arhus, Denmark

Introduction and objective: Recent studies suggest that only around

30–50% of children and adolescents with ADHD have an executive

function deficit (EFD). If taken at face value, these findings imply that

in half of ADHD cases the disorder is mediated by something other

than EFD. The present study investigates behavioural, cognitive, and

motivational aspects of functioning in school-age children with

ADHD with and without an executive function deficit (EFD).

Methods: Children with ADHD-EFD (n = 22) and children with

ADHD + EFD (n = 26) were compared on aspects of ADHD

behaviour, general cognitive ability, intra-individual response vari-

ability, affective decision-making, and delay aversion.

Results: Children with ADHD-EFD and children with ADHD + EFD

were comparable in terms of ADHD symptomatology and affective

decision-making. However, children with ADHD + EFD had signif-

icantly lower IQ and more intra-individual response variability than

no EFD counterparts. Children with ADHD alone appeared more

delay averse on the C-DT task than children with ADHD + EFD.

Conclusions: Some children with ADHD were primarily character-

ised by problems with executive functions and variability others by

problems with delay aversion supporting multi-pathway models of

ADHD.

Comparison of children with ADHD predominantly

inattentive and combined subtypes in terms of aspects

of everyday attention

Jurgen Lemiere1, Heidi Wouters2, Caroline Sterken3, Lieven Lagae2,Edmund Sonuga-Barke4,5, Marina Danckaerts1

1Child and adolescent psychiatry, UPC-KULeuven, Leuven, Belgium;2Department of Pediatric Neurology, University of Leuven Medical

School, University Hospitals KULeuven, Leuven, Belgium;


123

3Intensive Care Medicine, University Hospitals KULeuven, Leuven,

Belgium; 4Developmental Brain and Behaviour Unit, School of

Psychology, University of Southampton, Southampton, UK;5Department of Experimental Clinical and Health Psychology,

University of Ghent, Ghent, Belgium

Introduction and objective: At behavioural level, attention problems

are a key feature of ADHD. Recently, a new neuropsychological

instrument was developed to assess aspects of everyday attention:

Test of Everyday Attention for Children (TEA-Ch). The aim of the

current study was to investigate whether children with ADHD are

impaired on domains of attention, as measured with the TEA-Ch and

whether this instrument can differentiate between combined (ADHD-

C) and inattentive subtype (ADHD-I) of ADHD.

Methods: Sixty-four children with a diagnosis of ADHD (38 with

ADHD-C; 26 with ADHD-I) and 76 comparison children were included.

Results: Seven differences on six subtests between ADHD and con-

trol groups were found. However, the results of the logistic regression

analysis demonstrated that there is little evidence that these subtests

made independent contributions to differentiating ADHD cases from

controls. There was a significant difference between ADHD-C and

ADHD-I for one subtest. Confirmatory factor analysis shows that the

three factor structure in our ADHD-group achieved a poor fit.

Discussion and conclusion: Children with ADHD, irrespective of

subtypes demonstrated some problems on the TEA-Ch. Our study

provides further evidence against the discriminant validity of ADHD-

C and ADHD-I subtypes as defined by DSM-IV-TR.

References


(2005) ADHD subtypes: do they differ in their executive

functioning profile? Arch Clin Neuropsychol 20:457–477

2. Heaton SC, Reader SK, Preston AS, Fennell EB, Puyana OE, Gill

N, Johnson JH (2001) The test of everyday attention for children

(TEA-Ch): patterns of performance in children with ADHD and

clinical controls. Child Neuropsychol 7:251–264

3. Manly T, Anderson V, Nimmo-Smith I, Turner A, Watson P,

Robertson IH (2001) The differential assessment of children’s

attention: the test of everyday attention for children (TEA-Ch),

normative sample and ADHD performance. J Child Psychol


Motor skills in adolescent attention deficit/hyperactivity

disorder (ADHD): gender specific profiles of fine

and gross motor performance

Emma McIlveen-Brown1, Rosemary Tannock1,2

1Ontario Institute for Studies in Education (OISE), University of

Toronto, Toronto, Canada; 2Ontario Institute for Studies in Education

(OISE), Hospital for Sick Children, Toronto, Canada

Introduction and objectives: Across a wide age range, questionnaire

measures indicate that motor coordination abnormalities are more

pronounced in girls than boys with ADHD [1]. The current study

investigates fine and gross motor coordination skills in an adolescent,

ADHD sample.

Methods: Ninety participants (24% female), aged 13–18 years, with a

confirmed, DSM-IV ADHD diagnosis completed fine (beads in a box,

nut and bolt) and gross (heel-toe walk, standing on one foot) motor

tasks from the McCarron Assessment of Neuromuscular Develop-

ment—Revised (MAND).

Results: Compared to standardized norms, males performed poorly

on fine motor tasks whereas females performed poorly on both fine

and gross motor tasks. While motor performance was unrelated to

ADHD symptoms in males, performance on the beads in a box task

predicted inattentive symptoms in females.

Discussion: ADHD-related motor pathology was wider-ranging in

females than in males and was differentially correlated with ADHD

symptoms.

Conclusion: Measures of motor coordination and their brain-based

correlates can be used to provide suggestive explanations of gender

differences in the ADHD clinical profile.

References

1. Fliers E, Rommelse N, Vermeulen SH, Altink M, Buschgens CJ,

Faraone SV et al (2008) Motor coordination problems in children

and adolescents with ADHD rated by parents and teachers:

effects of age and gender. J Neural Transm 115(2):211–220

2. McCarron L (1997) McCarron assessment of neuromuscular

development: fine and gross motor abilities, revised edn.

Common Market Press, Dallas

3. Rucklidge JJ, Tannock R (2001) Psychiatric, psychosocial, and

cognitive functioning of female adolescents with ADHD. J Am


Executive functions in attention-deficit/hyperactivity

disorder

Deny Menghini1,2, Michela Di Trani1, Mariapia Casini1,Carmen Napolitano1, Stefano Vicari1

1Children’s Hospital Bambino Gesu, Rome, Italy; 2European

University, Rome, Italy

Introduction and objectives: Studies on executive functions (EF)

have documented several deficits in ADHD, but the nature of

deficits remains elusive and findings heterogeneous [1, 2]. By

investigating several aspects of EF, the present study was aimed at

better understanding the neuropsychological profile of ADHD

children.

Methods: Twenty ADHD (5 females; 8.4 ± 1.5 years) and 15 typi-

cally developing children (5 females; 7.5 ± 0.9 years) underwent to a

neuropsychological battery tapping sustained and selective attention,

shifting, planning, working memory and inhibition.

Results: In ADHD children were documented deficits in selective and

sustained auditory attention, inhibition and planning. However, some

aspects of EF were preserved (i.e. selective and sustained visual-

spatial attention, shifting, categorization and working memory).

Discussion: Our results documented that EF were not homogenously

impaired in ADHD children and that only some abilities should be

considered as the ‘‘core deficit’’ of EF in ADHD children.

Conclusion: The specific profile of EF emerged in ADHD children

need to be taken into account during the diagnostic phase and the

rehabilitation phase.

References

1. Barkley RA (1997) Behavioral inhibition, sustained attention,

and executive functions: constructing a unifying theory of

ADHD. Psychol Bull 121:65–94

2. Sergeant JA, Oosterlaan J, Van der Meere J (1998) Hyperactivity:

passed the point of no return? A cognitive energetic analysis. In:

Quay HC, Hogan AE (eds) Handbook of disruptive behavior

disorders. Plenum Press, New York


123

Basic impairments in regulating the speed-accuracy

tradeoff predict symptoms of ADHD

Martijn J. Mulder1, Dienke Bos1, Juliette M. H. Weusten1,Janna van Belle1, Sarai C. van Dijk1, Patrick Simen2,Herman van Engeland1, Sarah Durston1,3


Institute of Neuroscience, University Medical Center Utrecht,

Utrecht, The Netherlands; 2Center for the Study of Brain, Mind and

Behavior, Princeton University, Princeton, NJ, USA; 3Sackler

Institute for Developmental Psychobiology, Weill Cornell Medical

College, New York, NY, USA

Introduction and objective: ADHD is characterized by poor opti-

mization of behavior in the face of changing demands. Theoretical

accounts of ADHD have often focused on higher-order cogni-

tive processes and typically assume that basic processes are

unaffected. It is an open question whether this is indeed the case.

Methods: We explored basic cognitive processing in 25 subjects with

ADHD and 30 typically developing children and adolescents using a

perceptual decision making paradigm. We investigated whether

individuals with ADHD were able to balance the speed and accuracy

of simple decisions.

Results: We found impairments in optimization of the speed-accu-

racy tradeoff. Furthermore, these impairments were directly related to

the hyperactive and impulsive symptoms that characterize the

ADHD-phenotype.

Discussion and conclusion: These data suggests that impairments in

basic cognitive processing are central to the disorder. This calls into

question conceptualizations of ADHD as a ‘higher-order’ deficit, as

such simple decision processes are at the core of almost every para-

digm used in ADHD research.

ADHD children do have problems with grammar

Esther Parigger1, Anne Baker1, Jan de Jong1

1UvA/ACLC, Amsterdam, The Netherlands

Introduction and objective: The aim of the current study is to shed

more light on morpho-syntactic language problems of children with

ADHD.

Methods: Children with ADHD (n = 26) were compared to SLI

(n = 14) and TD children (n = 22). Four different measures of

morpho-syntactic performance were selected.

Results: The scores of the ADHD group fall in between the scores of

the SLI and TD groups on two of four variables and are not signifi-

cantly different from the TD group on two other variables. However,

a more in-depth analysis shows that nearly 8% of the children with

ADHD score above cut-off on all four morpho-syntactic measures, as

opposed to only 0% of the children with TD.

Discussion: Morpho-syntactic problems of ADHD children are not

always visible if group differences are considered, probably due to the

large variation in scores. However, some ADHD children do have

problems with grammar.

Conclusion: The quite robust morpho-syntactic language problems of

these ADHD children should be registered more often. Such problems

can, for example, have a large effect on school performance.

References

1. Geurts H, Verte S, Oosterlaan J, Roeyers H, Hartman CA, Mulder

EJ et al (2004) Can the children’s communication checklist

differentiate between children with autism, children with ADHD

and normal controls? J Child Psychol Psychiatry 45(8):1437–

1453

2. Redmond SM (2005) Differentiating SLI from ADHD using

children’s sentence recall and production of past tense morphol-

ogy. Clin Linguist Phon 19:109–127

3. Tannock R, Schachar R (1996) Executive dysfunction as an

underlying mechanism of behavior and language problems in

attention deficit hyperactivity disorder. In: Beitchman JH, Cohen

NJ, Konstantareas MM, Tannock R (eds) Language, learning and

behavioral disorders. Developmental, biological and clinical

perspectives. Cambridge University Press, Cambridge, pp 128–

156

Intellectual ability in children with ADHD

Quintero Javier1, N. Garcia-Campos2, Mercedes Loro2,Isabel Miernau3, J.A. Herrera Pino4

1Hospital Infanta Leonor, Universidad Complutense de Madrid,

Madrid, Spain; 2Clınica Doctor Quintero, Madrid, Spain;3Neurobehavioral Institute of Madrid, Madrid, Spain;4Neurobehavioral Institute of Miami, Miami, FL, USA

Introduction and objective: Several studies point to the possibility

of a decreased level of global intellectual ability in patients with

ADHD.

Methods: Participants selected from outpatient facility during 2-year

period (n = 957); and divided in two groups; those diagnosed with

ADHD (n = 470; 376 males and 94 females) and those with other

diagnosis (n = 487; 258 males and 229 females). IQ was test with

WISC-IV.

Results: The mean full scale IQ found were:

ADHD Mean SD N

No ADHD 106.04 16.584 487

ADHD 103.09 14.367 470

Total 104.59 15.597 957

A comparison of the means of both samples a statistically sig-

nificant difference was found [F(df 1,955) = 8.635, p \ 0.01]. An

analysis by gender revealed that the statistical differences held for

boys with ADHD and without ADHD [F(df 1,632) = 11.083,

p \ 0.01], but no statistical significance was found amongst females

[F(df 1,321) = 2.867, p = 0.09].

Conclusion: The findings of this study suggest that children with

ADHD present a lower full scale IQ than children without ADHD.

However, the difference may be statically difference, the clinical

signification may be low.

References

1. Aylward GP (2002) Cognitive and neuropsychological outcomes:

more than IQ scores. Ment Retard Dev Disabil Res Rev 8(4):234–

240

2. Biederman J, Faraone SV (2005) Attention-deficit hyperactivity

disorder. Lancet 366(9481):237–248

3. Herrera Pino JA; Quintero Gutierrez del Alamo FJ, Garcia

Alvarez R (2009) Fundamentos Neuropsicologicos en TDAH; en


123

Trastorno por Deficit de Atencion a lo Largo de la Vida. Elsevier,

Barcelona

Planning function in ADHD; a comparison with early-

onset psychosis (EOP) and autistic spectrum disorder

(ASD)*

A.B. Ramırez-Gonzalez1, M.S. Centeno-Collado1, M. Ruiz-Veguilla1,J.M. Granados-Moreno1, M.D. Salcedo-Marın1,M.L. Barrigon-Estevez2, J.L. Rubio- Gomez1, M. Ferrin1,2.

1NeuroDevelopmental Psychiatry Research Unit (NPD), Jaen, Spain;2Institute of Psychiatry, London, UK

*Preliminary results presented during the Eunethydis conference,

Winchester 2009

Corresponding author: [email protected]

Introduction: Impairments in executive function are thought to play

a key role in a variety of developmental disorders including ADHD

[1].

Objective: To explore planning skills in children/adolescents with

different neurodevelopmental disorders (ADHD n = 42, early onset

psychosis n = 58, and ASD n = 37), and to compare them with a

control group (n = 31).

Methods: We used the Zoo Map task [2, 3]. The ZM assesses ability

to organize and implement a plan in both non-structured and struc-

tured conditions. We registered planning time, total time for

completing the task, and number of errors.

Results: ADHD group needed more time for planning when com-

pared to the rest of the groups (p \ 0.05) but only for the non-

structured condition. ASD made more commission errors when

compared to ADHD and controls in both the structured and non-

structured versions (p \ 0.05). EOP planning function was the

poorest in all variables when compared to the rest of the groups.

Discussion: ADHD subjects may present with deficits in planning

task, but especially in the non-structured situations. Neurodevelop-

mental disorders present differences in planning function when

compared between them.

References

1. Pennington BF, Ozonoff S (1996) Executive functions and

developmental psychopathology. J Child Psychol Psychiatry

37(1):51–87

2. Lawrence V, Houghton S, Tannock R, Douglas G, Durkin K,

Whiting K (2002) ADHD outside the laboratory: boys’ executive

function performance on tasks in videogame play and on a visit to

the zoo. J Abnorm Child Psychol 30(5):447–462

3. Lawrence V, Houghton S, Douglas G, Durkin K, Whiting K,

Tannock R (2004) Executive function and ADHD: a comparison

of children’s performance during neuropsychological testing and

real-world activities. J Atten Disord 7(3):137–149

Computer console use in children with ADHD

and ODD: relationship with WM

Sinead M Rhodes1*, Joanne Park2, Sarah Seth3, David R. Coghill3

1Department of Psychology, University of Strathclyde, Graham Hills

Building, 40 George Street, Glasgow G1 IQE, UK; 2Bute Medical

School, University of St Andrews, St Andrews, Fife, KY16 9TS, UK;3Division of Medical Sciences, Centre for Neuroscience (Psychiatry

and Behavioural Sciences), University of Dundee, Ninewells Hospital

and Medical School, Dundee DD1 9SY, UK

Introduction and objective: We investigated computer console use

and its relationship to working memory (WM) in children with

ADHD and ODD.

Methods: The groups comprised age-matched drug naıve boys with

(1) ADHD (N = 16), (2) ADHD + ODD (N = 22), (3) ODD

(N = 14), and (4) typically developing children (N = 20). Partici-

pants completed a self-report questionnaire which examined

frequency and type of console use and WM component tasks and

memory tasks from the CANTAB battery.

Results: All four groups reported spending similar time daily using

computer games and owned a similar number of consoles. Both

ADHD and ODD were characterised by a range of WM impairments

but the groups showed variations in their pattern of performance.

Children with ADHD showed a broader range of deficits within the

spatial domain while verbal deficits were more closely associated

with ODD. ADHD + ODD was characterised by an additive effect of

these deficits. In children with ADHD + ODD increased console

ownership was positively related to spatial span and executive spatial

WM.

Conclusion: Computer use may be positively related to WM in

combined ADHD + ODD.

Attentional and executive indexes of the Conners’

continuous performance test (CCPT) in a sample

of adolescents with ADHD. Can the CCPT be claimed

as a endophenotype of ADHD?

T.S. Rivero1, A.A.L. de Souza1, M.C. Miranda1, O.F.A. Bueno1

1Psychobiology Department, Universidade Federal de Sao Paulo, Sao

Paulo, Brazil

Introduction and objectives: This study investigated the perfor-

mance of a clinical sample of adolescents with ADHD in CCPT.

Methods: Twenty-eight subjects with ADHD (17 male) aged between

12 and 18 years. The results in each of the 15 measures of CCPT

were compared between the ADHD and control group. Besides the

analysis of each measure separately, a factor analysis proposed by

Egeland and Kovalick-Gran [1] was performed.

Results: The ADHD group showed deficit in 13 of the 15 measures

evaluated by CCPT when compared to the control group. The five

factors analysis shown that both subtypes of ADHD had poor per-

formance in relation to vigilance (p = 0.001), focused attention

(p = 0.001) and sustained attention (p = 0.001), when compared

with control subjects.

Discussion and conclusion: The analysis of 15 measures in the

ADHD group supports that the CCPT is a possible candidate endo-

phenotype test for the evaluation of attentional and executive deficits

in ADHD.

References

1. Egeland J, Kovalik-Gran I (2009) Validity of the factor structure

of Conners’CPT. J Atten Disord

2. Chen WJ, Hsiao CK, Hsiao LL, Hwu HG (1998) Performance of

the continuous performance test among community samples.

Schizophr Bull 24(1):163–167


123

Videogame and ADHD-like behavior in healthy

adolescents

T.S. Rivero1, A.A.L. de Souza1, M.C. Miranda1, O.F.A. Bueno1

1Psychobiology Department, Universidade Federal de Sao Paulo, Sao

Paulo, Brazil

Introduction and objectives: We evaluated the impact of videoga-

ming on five distinct domains of attention in healthy adolescents,

using the CCPT [2].

Methods: A total of 360 adolescents (199 females), aged between 12

and 17 years have been evaluated. 174 play videogame (VG) and 186

do not (NVG). The CCPT provide a range of 15 different measures

merged into five factors using the Egeland and Kovalik [1] model.

Results: Interactions among sex, age and use of videogame were not

found. However, differences between VG and NVG were found for

hyperactive/impulsive factor (VG -0.28 ± 0.79, NVG 0.27 ± 1.01;

F = 20,214; p \ 0.001) in which the VG showed an impaired pattern

in high speed performance, an increase in commission errors, and a

poorer speed/accuracy trade-off.

Discussion and conclusion: We conclude that videogame use is

associated with an increase of hyperactive and impulsivity measures

in adolescents. These results suggest that videogame use could elicit

an ADHD-like behavior in healthy adolescents. This finding presents

a potential clinical implication of video gaming as part of training

process to improve control skills in ADHD patients.

References

1. Egeland J, Kovalik-Gran I (2009) Validity of the factor structure

of Conners’CPT. J Atten Disord

2. Conners CK, Epstein JN, Angold A, Klaric J (2003) Continuous

performance test performance in a normative epidemiological

sample. J Abnorm Child Psychol 31:555–562

Is there an executive dysfunction subtype

within ADHD?

Bethan A. Roberts1, Monica Gremillion1, Michelle M. Martel1,Joel T. Nigg2

1Psychology Department, University of New Orleans, New Orleans,

USA; 2Psychiatry Department, Oregon Health and Sciences

University, Oregon, USA

Background: Although ADHD has often been defined by its exten-

sive associated executive function (EF) impairments, effect sizes of

EF association fall in only the medium range [1]. This suggests a key

question: Is there a subtype, or subgroup, of individuals within the

ADHD diagnostic category who are characterized by EF

impairments?

Methods: Participants were 373 children between the ages of 6 and

13 recruited through the community who completed a multi-stage,

diagnostic screening procedure. Children completed laboratory EF

tasks (Stop, Trails).

Results: K-means cluster analysis conducted in SPSS generated a

two-cluster solution. Cluster 1 (n = 128) was characterized by poor

EF. Cluster 2 (n = 245) was characterized by better EF. These

clusters were externally validated with inattentive, hyperactive-

impulsive, and ODD symptoms via MANOVA. The MANOVA was

significant [F(3,352) = 7.03, p \ 0.01], with effects for ODD

symptoms [F(1) = 13.88, p \ 0.01], but not for inattentive

(p = 0.07) or hyperactive-impulsive (p = 0.15) symptoms. The chi-

square statistic for subtype differences was significant [V2(3) = 9.43;

p = 0.02].

Conclusions: Children characterized by an executive dysfunction

subtype of ADHD are more likely to fall within the ADHD-C subtype

and exhibit more ODD symptoms.

References

1. Nigg JT, Willcutt EG, Doyle AE, Sonuga-Barker EJS (2005)

Causal heterogeneity in attention-deficit/hyperactivity disorder:

do we need neuropsychologically impaired subtypes? Biol


Father involvement in the learning of children

with and without attention-deficit hyperactivity

disorder

Maria A. Rogers1, Rosemary Tannock1, Judith Wiener2

1Hospital for Sick Children, Toronto, ON, Canada; 2University of

Toronto, Toronto, ON, Canada

Introduction and objectives: Fathers’ involvement in children’s

learning is associated with higher child achievement and more posi-

tive school attitudes. However, no studies to date have examined

fathers’ educational involvement in children with ADHD. Therefore,

this study sought to compare fathers and mothers of children with and

without ADHD regarding their school-focused interactions in the

home.

Method: Fathers and mothers of children with and without ADHD

were administered the Family-School Questionnaire (FSQ)—a self-

report Likert scale assessing mothers’ and fathers’ home-based aca-

demic involvement with their children.

Results: Results revealed that fathers of children with ADHD

reported being more disengaged from their children’s learning and

using more coercive and punitive interactions regarding their chil-

dren’s achievement. There were no significant differences for

mothers.

Discussion: This study suggests that fathers of children with ADHD

are disengaged from their children’s learning and their involvement in

characterized by controlling, ineffective interactions.

Conclusion: These findings underscore the challenges facing fathers

of children with ADHD in supporting their children’s learning. Cli-

nicians should be aware of these challenges and incorporate this

knowledge into assessment and treatment practices.

References

1. DuPaul GJ, Stoner G (2003) ADHD and learning difficulties:

what is the connection? In: DuPaul GJ, Stoner G (eds) ADHD in

the schools: assessment and intervention strategies. Guilford

Press, New York, pp 72–108

2. Fan X, Chen M (2001) Parental involvement and students’

achievement: a meta-analysis. Educ Psychol Rev 13(1):1–22

Executive functions in preschool children with ADHD

and disruptive behavior disorders

K. Schoemaker1,2, T. Bunte2, S.A. Wiebe3, K.A. Espy4, M. Dekovic1,W. Matthys1,2

1Department of Child and Adolescent Studies, Utrecht University,

Utrecht, The Netherlands; 2Child Psychiatry Department, University


123

Medical Center, Utrecht, The Netherlands; 3Department of

Psychology, University of Alberta, Edmonton, Canada; 4Psychology

Office of Research, University of Nebraska, Lincoln, USA

There is a body of research showing deficits in executive functions

(EF) in school aged children with attention-deficit/hyperactivity dis-

order (ADHD) and, to a lesser extent, in children with a disruptive

behavior disorder (DBD), i.e., oppositional defiant disorder or con-

duct disorder. Although these disorders emerge already during the

preschool years, few studies have been conducted on EF in preschool

children with ADHD and DBD. In this study, 205 children between

the age of 42 and 65 months participated: 61 were diagnosed with

ADHD, 34 with DBD, 52 with both ADHD and DBD, and there were

58 typically developing children. Five tasks that have been developed

to assess EF in preschool children were used [1]. Factor analysis

revealed an inhibition factor and a working memory factor. Children

from all three clinical groups performed significantly worse on the

inhibition factor than the NC group, also after covariation with IQ.

There were no significant differences on the WM factor. Preschool

children with ADHD, DBD and ADHD + DBD have deficits in EF in

the inhibition domain, but not in the WM domain.

Reference

1. Wiebe SA, Clark CAC, Chevalier N, Sheffield T, Nelson JM,

Espy KA (2010) Determining the structure of executive control in

3-year-old children: further evidence for unity. J Exp Child

Psychol (in review)

Neuropsychological heterogeneity attention deficit

hyperactivity: a broad brush approach

Sarah Seth1,2, Helen Smith1, Keith Matthews1, David Coghill1

1Division of Medical Sciences, Centre for Neuroscience, University

of Dundee, Dundee, Scotland, UK; 2NHS Tayside, Dundee, Scotland,

UK

Introduction and objective: Previous studies have attempted to

describe the neuropsychological heterogeneity inherent to ADHD

most of these have used fairly narrow batteries of neuropsychological

tasks. We measured performance on a broad based battery of tasks

that tap in to six key domains of neuropsychological functioning

Methods: Eight-six drug naive boys with ADHD were compared to

66 healthy controls on a battery of well-validated tasks measuring

working and non-working memory, delay aversion, response inhibi-

tion, temporal processing, and decision-making.

Results: Whilst deficits, with moderate effect sizes were found on

eight measures spanning all domains, except response inhibition. The

most common deficits were on the non-working memory (27%),

anticipation (28%) and tapping (30%) tasks. 19% of ADHD boys

having no deficits, 35% one deficit, 23% two and only 23% C3.

Discussion: Even though we have used a much broader battery of

tasks than has been used in previous studies the pattern of deficits is

strikingly similar to several previously reported datasets [1–3]. There

is minimal crossover between the different neuropsychological

domains.

Conclusions: A broad brush approach is essential to furthering our

understanding of ADHD.

References


TE, Ferrero F, Morgan CL, Faraone SV (2004) Impact of

executive function deficits and attention-deficit/hyperactivity

disorder (ADHD) on academic outcomes in children. J Consult

Clin Psychol 72(5):757–766

2. Coghill D (2010) Heterogeneity in hyperkinetic disorder. Uni-

versity of Dundee, Dundee.

3. Nigg JT, Willcutt EG, Doyle AE, Sonuga-Barke EJ (2005)

Causal heterogeneity in attention-deficit/hyperactivity disorder:

do we need neuropsychologically impaired subtypes? Biol

Psychiatry 57(11):1224–1230

Validation of computerized executive function tests:

with ADHD children

Min-Sup Shin1,*, Ryemi Do1, Su-Jin Kim1, Mi-Young Park1

1Division of Child and Adolescent Psychiatry, Seoul National

University Children’s Hospital, Seoul, South Korea

*E-mail: [email protected]

Introduction and objective: ADHD is described as a disorder of the

executive function. We have developed the computerized tests to

assess executive function (EF), including planning (P), cognitive

flexibility (CF), behavior inhibition (BI) and attention control (AC).

The aim of this study is to evaluate the construct validity of the tests

we had developed.

Methods: Normative sample was 1,350 healthy Korean children;

about 100 children for each age group from 4 to 12 years. We

compared the performances between 31 ADHD and 31 healthy

children.

Results: There was significant difference between ADHD and healthy

children in EF index [F(1,60) = 26.22, p \ 0.01]. ADHD children

showed lower scores than healthy children in P [F(1,60) = 20.54,

p \ 0.01], CF [F(1,60) = 8.30, p \ 0.01], BI [F(1,60) = 5.61,

p \ 0.05], and AC [F(1,60) = 11.64, p \ 0.01] tests.

Discussion: We found ADHD children to show poor performances in

EF tests than healthy children.

Conclusion: The computerized EF test could be valid and effective to

discriminate ADHD from healthy children.

Working memory and ADHD symptoms in preschool

children

Annette Holth Skogan1, Heidi Aase1,2, Pal Zeiner1,Anne-Grethe Urnes1, Jens Egeland3

1Oslo University Hospital Ulleval, Oslo, Norway; 2Division of Mental

Health, Norwegian Institute of Public Health, Oslo, Norway;3Vestfold Mental Health Care Trust, Tønsberg, Norway

Working memory (WM) functions are necessary for several higher-

order cognitive processes, and have been found to be compromised in

ADHD [1, 2]. The object of the present study is to examine whether

WM impairments are present in preschool children with significant

ADHD symptoms and how possible WM deficits are related to

behavioural symptoms of ADHD and intellectual ability. The present

study included 510 children aged 38–44 months, recruited from the

Norwegian Mother and child cohort study [3]. Measures of working

memory and intellectual ability from the Stanford-Binet 5 were

subjected to categorical analyses according to three groups (a group

with significant ADHD symptoms, a group with significant symptoms

of other clinical disorders, and a group without clinical symptoms);


123

and to dimensional analyses according to ratings of symptoms of

inattention, hyperactivity and impulsiveness. Preliminary analyses

show that children with elevated levels of ADHD symptoms scored

significantly poorer than children without ADHD symptoms on

measures of intellectual ability and working memory. The ADHD-

related reduction in WM scores were partly independent of variations

in intellectual ability.

References

1. Mahone EM, Hoffman J (2007) Behavior ratings of executive

function among preschoolers with ADHD. Clin Neuropsychol

21:569–586

2. Burgess GC, Depue BE, Ruzic L et al (2010) Attentional control

activation relates to working memory in attention deficit-hyper-

activity disorder. J Biol Psychiatry (in press)

3. Magnus P, Irgens LM, Haug K et al (2006) Cohort profile: the

Norwegian Mother and Child Cohort Study (MoBa). Int J

Epidemiol 35:1146–1150

Noise enhances sensory processing and cognition. The

dopamine hypothesis of the moderate brain arousal

model tested in a rat model of ADHD

Goran Soderlund2,4, Erik Palsson1, Daniel Klamer1, Filip Bergquist3

1Department of Pharmacology, Institute of Neuroscience and

Physiology, The Sahlgrenska Academy, University of Gothenburg,

Goteborg, Sweden; 2Department of Linguistics, Stockholm

University, Stockholm, Sweden; 3Department of Clinical

Neuroscience and Rehabilitation, Institute of Neuroscience and

Physiology, The Sahlgrenska Academy, University of Gothenburg,

Goteborg, Sweden; 4Department of Psychology, University of

Southampton, Southampton, UK

Introduction and objectives: Noise facilitation of cognitive func-

tions is consistent with stochastic resonance, where a certain amount

of noise improves performance. The moderate brain arousal model

(Sikstrom and Soderlund 2007) proposes that brain dopamine levels

influence the amount of noise required for maximal performance,

and predicts that ADHD subjects with ‘‘low’’ dopamine transmis-

sion, require more noise than control subjects for maximal

performance.

Methods: The effect of background acoustic noise on acoustic startle

and pre-pulse inhibition (PPI) was measured in the spontaneously

hypertensive (SH) rat model of ADHD and in control strains. The

relation between noise and dopamine transmission was evaluated with

microdialysis, methylphenidate treatment and 6-hydroxydopamine

lesions.

Results: Prefrontal dopamine release was blunted in SH rats

during the somatosensory gating task of PPI. Noise facilitated PPI

in all strains, but considerably more in SH rats. Interference with

dopamine transmission produced small or no effects on startle and

PPI.

Discussion: Dopamine transmission in the prefrontal cortex of SH

rats is characteristic for high dopamine re-uptake activity. Minor

influence of noise on dopamine transmission, and vice versa, suggest

that sensory noise and dopamine act independently on cognitive

processing.

Keywords: Startle reflex, Pre-pulse inhibition, White noise, Sto-

chastic resonance, Dopamine

Impaired working memory in ADHD: deficit or delay?

Paula Sowerby1, Simon Seal1, Brent Alsop1, Gail Tripp2

1University of Otago, Dunedin, New Zealand; 2Okinawa Institute of

Science and Technology, Okinawa, Japan

Objective: To further define the nature of working memory (WM)

impairments in children with combined-type attention deficit hyper-

activity disorder (ADHD).

Method: Children with ADHD (n = 40) and an age and gender-

matched control group completed two measures each of visuo-spatial

and verbal WM. The effects of age and learning/language difficulties

on performance were evaluated.

Results: Children with ADHD obtained significantly lower scores

than controls on measures of both visuo-spatial and verbal WM. The

impairments in verbal WM were age related. Removal of children

with comorbid learning/language difficulties and their matched con-

trols reduced group differences, but did not fully account for the WM

deficits.

Conclusions: Children with ADHD exhibit impaired visuo-spatial WM

performance. Younger (less than 8 years), but not older, children with

ADHD demonstrate impairments in verbal WM. This latter result may

explain the previously reported inconsistent performance of children

with ADHD on measures of verbal WM. The importance of taking a

developmental perspective in working memory research is stressed.

Keywords: ADHD, Working memory, Developmental perspective

Long-term cognitive outcome of hyperactive children:

results from the Newham longitudinal study

Mario Speranza1,2, Argyris Stringaris1, Eric Taylor1

1Centre Hospitalier de Versailles, Universite Paris-Sud, Universite

Paris Descartes, UMR-S0669, INSERM U669, Paris, France;2Institute of Psychiatry, King’s college, London, UK

Introduction and objective: Investigate, in a community-based

sample, the impact of executive function deficits on the long-term

cognitive outcome of hyperactive children.

Methods: A 20-year follow-up of hyperactive (N = 40) and control

(N = 24) children identified at age 7 as showing pervasive hyperac-

tivity (HA) and/or executive function deficits (EFDs). Cognitive

outcome at follow-up was investigated with the CANTAB battery.

Main and interactive effects of HA and EFDs were explored with a

two-way analysis of variance adjusting on IQ.

Results: At follow-up, there was a significant interactive effect of HA

and EFDs on the cognitive outcome of grown-up children. This effect

was unrelated to initial IQ level.

Discussion: Possible explanations: (1) EFDs exacerbate the expres-

sion of HA; (2) EFDs represent a marker for other risks affecting

hyperactive children; (3) Negative effects of EFDs in controls are

buffered by protective factors.

Conclusion: This study suggests that EFDs in hyperactive children

raise the risk of negative cognitive outcomes in adulthood. Further

research is needed to identify the specific pathways involved.

References

1. Taylor E, Chadwick O, Heptinstall E, Danckaerts M (1996)

Hyperactivity and conduct problems as risk factors for adolescent

development. J Am Acad Child Adolesc Psychiatry 35(9):1213–1226


123


TE, Ferrero F, Morgan CL, Faraone SV (2004) Impact of

executive function deficits and attention-deficit/hyperactivity

disorder (ADHD) on academic outcomes in children. J Consult

Clin Psychol 72(5):757–766

The influence of error processing on skill acquisition

in children with ADHD

Helen Tam1, Amy N. Moore1, Cynthia L. Huang-Pollock1

1Department of Psychology, The Pennsylvania State University,

Pennsylvania, USA

Introduction and objective: Error-monitoring processes, defined as

slowdown in reaction time on the first correct item following an error,

are important to skill acquisition and may be impaired in children

with ADHD [1, 2]. We sought to determine whether error related

processes may explain poor skill acquisition in ADHD.

Methods: Children with ADHD (n = 28), non-ADHD controls

(n = 38), and young adults (n = 37) completed 400 trials (5 blocks)

of a categorization learning paradigm [3].

Results: In the early stages of the task, children with and without

ADHD exhibited less post error slowing (PES) than adults

[F(2,100) = 3.53, p = 0.03, gp2 = 0.07]. PES predicted overall

accuracy for adults [F(1,35) = 10.78, p \ 0.01, R2 = 0.24] but not

for children [ADHD: F(1,24) = 0.00, p = 0.95, R2 = 0.00; control:

F(1,36) = 0.78, p = 0.38, R2 = 0.02]. PES predicted accuracy in the

final block of trials (i.e., when maximal learning was achieved) for

adults [F(1,35) = 10.24, p \ 0.01, R2 = 0.23] and controls

[F(1,36) = 6.41, p = 0.02, R2 = 0.15], but not for children with

ADHD [F(1,24) = 1.42, p = 0.25, R2 = 0.06].

Discussion/conclusion: The ability to utilize performance feedback is

not fully developed in school age children. Compared to controls,

children with ADHD show less behavioral responsiveness to error in a

learning task. These results have implications for the development of

psychoeducational programs for children with ADHD.

References

1. Sergeant J, Van der Meere J (1988) What happens after a

hyperactive child commits an error? Psychiatry Res 24(2):157–

164

2. Schachar RJ, Chen S, Logan GD, Ornstein TJ, Crosbie J,

Ickowicz A, Pakulak A (2004) Evidence for an error monitoring

deficit in attention deficit hyperactivity disorder. J Abnorm Child

Psychol 32(3):285–293

3. Maddox WT, Ashby FG, Bohil CJ (2003) Delayed feedback

effects on rule-based and information-integration category learn-

ing. J Exp Psychol Learn Mem Cogn 29(4):650–662

In Harm’s way: adults with attention-deficit/

hyperactivity disorder in high-risk situations

Mairin Taylor1,*, J. Rucklidge1, R. Kuijer1

Department of Psychology, University of Canterbury, Private Bag

4800, Christchurch, New Zealand

*E-mail: [email protected]

Introduction and objective: We investigated whether adults with

ADHD were more likely to engage in very high risk behaviours and

also more likely to have been victims of violence.

Methods: Thity-five adults with ADHD and 32 controls were

recruited. Participants were assessed on measures of high-risk

behaviours including: self harm, suicidal behaviours and carrying

weapons and engaging in physical fights; as well as victimisation.

Mediating variables were also assessed.

Results: This study is currently in progress. Of the cases analyzed so

far, significant differences were found between the ADHD and con-

trol groups on measures of life-time history of self-harm; suicidal

ideation; carrying a weapon; domestic violence victimisation and

experience of emotional abuse in childhood (all p \ 0.01).

Discussion: Large and significant results were found. Awareness of

the risks for adults with ADHD will enable clinicians to target

interventions. The mechanisms of these behaviours may assist

understanding of high risk behaviours in the general population.

Conclusion: ADHD in adulthood is gaining awareness as a disorder

that may contribute to an individual’s behaviours that may be unsafe

for themselves and for others, as supported by this research.

Exploring white matter integrity in children

with ADHD, as measured by diffusion tensor imaging

H. van Ewijk1

1Department of Clinical Neuropsychology, VU University


Introduction and objective: Magnetic resonance imaging (MRI) has

proven to be a useful tool in ADHD research. Converging evidence

suggests that abnormalities in brain structure and functioning might

play an important role in the pathophysiology of the disorder.

However, the role of white matter (WM) tracts is still underex-

plored. Diffusion tensor imaging (DTI) allows us to examine WM

integrity at a microstructural level. Most commonly used measures

include fractional anisotropy (FA), mean diffusivity (MD) and

apparent diffusion coefficients (ADC). Altogether, these measures

represent the direction and extent of water diffusion in the brain,

indicative of the organization and orientation of WM tracts and

myelination.

Methods: A thorough literature search resulted in nine studies using

DTI to study WM integrity in children with ADHD.

Results: Preliminary findings suggest reduced fibre or myelination

density in several WM tracts throughout the brain in children ADHD,

as well as less diffusion restriction.

Discussion and conclusion: Altogether, these preliminary findings

suggest a disruption of the intactness and organization of WM tracts

throughout the brain, and put DTI forward as a promising technique in

ADHD research.

References

1. Bush G, Valera EM, Seidman LJ (2005) Functional neuroimaging

of attention-deficit/hyperactivity disorder: a review and suggested

future directions. Biol Psychiatry 57:1273–1284

2. Castellanos FX, Lee PP, Sharp W, Jeffries NO, Greenstein DK,

Clasen LS, Blumenthal JD, James RS, Ebens CL, Walter JM,

Zijdenbos A, Evans AC, Giedd JN, Rappoport JL (2002)

Developmental trajectories of brain volume abnormalities in

children and adolescents with attention-deficit/hyperactivity dis-

order. JAMA 228:1740–1748


123

A review on the predictive value of neuropsychological

measures on ADHD status

Marloes van Lieshout1

1Department of Clinical Neuropsychology, VU University


Background: In the few longitudinal studies performed is shown

that a substantial group of children with ADHD persists in prob-

lematic ADHD behavior. It is important to understand what

characterizes the remittent versus the persistent ADHD group.

Since more and more studies suggest neuropsychological dysfunc-

tioning as one of the underlying mechanisms leading to

problematic behavior, this review focuses on longitudinal studies

using neuropsychological measures at baseline as predictors for

later ADHD status.

Methods: A literature search resulted in a comparison of ten studies

that (1) represented longitudinal data, (2) used at least one neuro-

psychological measure at baseline that was related to later ADHD

status and (3) used DSM-III-R or DSM-IV criteria to diagnose

ADHD.

Results: Preliminary results show that most neuropsychological

measures at baseline were predictive of later ADHD status. In par-

ticular, errors on a CPT and on a go/no-go task as well as TIQ were

predictors for ADHD status replicated in several studies.

Conclusion: These findings support the idea that assessing neuro-

psychological functioning at early childhood may be fruitful to

establish a ‘risk profile’ for later ADHD status.

Keywords: Review, ADHD, Predictive value, Neuropsychological

functioning, Longitudinal studies

A novel perspective on interference control

and distraction in ADHD

Rosa van Mourik1

1Department of Clinical Neuropsychology, Vrije Universiteit


Introduction and objectives: Children with ADHD show enhanced

distractibility. The neural mechanisms that lead to these deficits are

poorly understood.

Methods: Interference control is measured with an auditory version

of the Stroop Color Word task, and distractibility with an eco-

logical valid distraction paradigm. ERPs are measured during both

tasks.

Results: Remarkably, children with ADHD show equal interference

as compared with controls. However, the neural process that is related

to resolve interference (the sustained potential) was frontal in ADHD,

and parietal in controls. Novel, irrelevant information can have ben-

eficial effects on performance: children react more accurate, an effect

that is most pronounced in the ADHD group. At the electrophysio-

logical level, a larger orienting reaction (late P3a) was found in

ADHD as compared with controls.

Discussion and conclusion: While children with ADHD are more

distracted at the electrophysiological level, this distraction has a

facilitating effect on maintaining task performance. Enhancement of

performance in children with ADHD might be the result of a more

optimal arousal, induced by novel sounds. Interference control may

not be disrupted at the behavioral level despite neurophysiological

differences.

Poster Sessions F: Pharmacological andNon-pharmacological Treatment

Cognitive rehabilitation of attention using Pay

Attention! Program: a case study

D.L.F. Barbosa1, M.C. Miranda1, M. Muzskat1, S. Rizzutti1,D.A. Dias1, K.P. Rodrigues1, L.F.S. Coelho1, O.F.A. Bueno1

1Federal University of Sao Paulo, Sao Paulo, Brazil

Introduction and objectives: In attention deficit and hyperactivity

disorder (ADHD)—that has great negative impact in the daily—

therapeutic intervention becomes necessary. Pay Attention!—a chil-

dren’s attention process training program intends to treat the

difficulties of sustained, selective, alternated and divided attention [1,

2]. Then, this case study described an intervention process in peculiar

aspects of the attention using Pay Attention!Method: G.F.S, 13 years old, male, was evaluated with neurological

and psychiatric procedures and neuropsychological battery in the first

phase. The second phase contained the training using Pay Attention!in 20 sessions using placebo. In the third phase, the efficacy of the

program was analyzed by comparing the evaluations results before

and after the intervention.

Results: The results showed improvement in some attention, working

memory and behavioral scales measures.

Discussion: the results indicate better speed and orientation of the

attention and smaller impulsiveness. Furthermore, behavioral adjust-

ment was improved too.

Conclusions: Basis on this case study is possible establishing that the

attentional training using Pay Attention! has possibility to show

efficiency for the ADHD treatment.

References

1. Sohlberg MM, Mateer CA (1989) Introduction to cognitive

rehabilitation: theory and practice. The Guillford Press, New York

2. Sohlberg MM, Mateer CA (2001) Cognitive rehabilitation. The

Guillford Press, New York

Effects of atomoxetine, desipramine, d-amphetamine,

methylphenidate and clonidine in a preclinical model

of attention deficit hyperactivity disorder:

the impulsive-related behaviour in juvenile wistar rats

Jean-Charles Bizot1, Sabrina David1, Fabrice Trovero1

1Key-Obs SAS, 3 allee du Titane, 45100 Orleans, France

Tel: +33-238646068; Fax: +33-238769497; E-mail:

[email protected]; website: http://www.key-obs.com

Introduction and objective: Impulsivity is a core symptom of

attention deficit/hyperactivity disorder (ADHD). A previous study

demonstrated that methylphenidate decreased impulsivity in juvenile

rats [1]. The aim of the present study was to confirm this observation

and to determine whether other drugs potentially effective for the

treatment of ADHD alter impulsivity in this experimental procedure.

Methods: Juvenile Wister rats were trained in a T-maze to choose

between a small-and-immediate food reward and a large-but-30 s-

delayed food reward. The effects of drugs were studied on the per-

formance of animals at 30–40 days of age.

Results: The number of choices of the large-but-delayed reward was

increased by methylphenidate (3 mg/kg), D-amphetamine (1, 2 mg/


123

kg), atomoxetine (1 mg/kg), desipramine (8, 16 mg/kg) and clonidine

(0.05 mg/kg).

Discussion: These results indicate that these five drugs improved

waiting ability, i.e. decreased impulsivity.

Conclusion: Given that these compounds are prescribed or potentially

effective for the treatment of ADHD [2], these data indicate that the

T-maze procedure in juvenile animals is suitable for testing the

therapeutic potential of drugs developed for the treatment of ADHD.

References

1. Bizot JC et al (2007) Psychopharmacology 193:215–223

2. Olfson M (2004) Am J Manage Care 10(4 Suppl):S117–S124

Effects of N-3 fatty acids (DHA and EPA) on cognitive

control and associated brain activity in ADHD:

a double-blind placebo controlled study

Dienke Bos1, Janna van Belle1, Juliette Weusten1, Marco Hoeksma2,Sheila Wiseman2, Sarah Durston1

1Neuroimaging lab, department of child- and adolescent psychiatry,

University Medical Centre Utrecht, Utrecht, The Netherlands;2Unilever Research and Development, Vlaardingen, The Netherlands

Introduction and objectives: Previous studies have shown that chil-

dren with attention deficit hyperactivity disorder (ADHD) may benefit

from dietary supplementation with omega-3 fatty acids (EPA and DHA).

The objective of this study is to determine the effects of EPA/DHA

supplementation on cognitive control and associated brain activity in

prefrontal and striatal areas.

Methods: Boys with ADHD (N = 40) and typically developing boys

(N = 40), aged 8–12 years, participate in a pre- and post treatment

fMRI session. Cognitive control will be assessed using a go/no-go

paradigm. During the intervention period children are randomised to

receive a supplement containing EPA/DHA or a placebo product on a

daily basis. Symptoms of ADHD will be assessed on a monthly basis.

Cheek cell and urine samples are collected for physiological analyses.

Results: At this point we are in the process of data acquisition and

researchers are blind to intervention group. Preliminary analysis of

the baseline scans to date (N = 4 typically developing, 5 ADHD)

shows decreases in activation for subjects in ADHD in cognitive

control regions, similar to other reports.

Keywords: ADHD, Omega-3, EPA/DHA, fMRI, Cognitive control

A cognitive behavioral planning and organization

treatment for adolescents with ADHD: a pilot study

investigating short-term effects

Bianca Boyer1, Marije Kuin2, Pier Prins1, Hilde M. Geurts1,Saskia van der Oord1,3

1University of Amsterdam, Amsterdam, The Netherlands; 2Lucertis

outpatient mental health clinic Zaandam, Zaandam, The Netherlands;3UVA-Virenze Academic Outpatient Mental Health Clinic,


In adolescents with ADHD problems with attention, planning and

organizing are more pronounced than in children with ADHD. How-

ever, at the same time, the parental control diminishes and greater

independence is demanded. This can cause enormous distress in

important areas of functioning such as school functioning, parent–

adolescent interaction and can even lead to mood or disruptive disorders

[1]. Since evidence-based psychosocial treatments for adolescents with

ADHD are lacking and positive results have been shown for a planning

and organizational training in adults with ADHD [3], we developed a

cognitive-behavioral treatment for adolescents with ADHD which

focuses on enhancing planning and organization skills. Restructuring of

negative cognitions and motivational interviewing techniques are also

included [2]. Ten adolescents, 12–16 years old, with an ADHD diag-

nosis and significant problems with planning and organizing participate

in this study. Pre-and posttest outcomes are assessed on three domains:

neuro-cognitive functioning, rating scales and ecologically valid out-

come measures. Preliminary results of this pilot study are presented.

Further, the design of the upcoming RCT (N = 250) is presented.

References

1. Barkley RA (2004) Adolescents with attention deficit/ hyperac-

tivity disorder: an overview of empirically based treatments. J

Psychiatr Pract 10:39–56

2. Kuin M, Boyer BE, and Van der Oord S (2010) Organisatie-

training: Werkboek plannen en organiseren voor jongeren met

ADHD op de middelbare school (Training organizational skills: a

manual to train planning and organisation skills of adolescents

with ADHD) Lucertis Kinder en Jeugd Psychiatrie/ Universiteit

van Amsterdam

3. Safren SA, Otto MW, Sprich S, Winett CL, Wilens TE,

Biederman J (2005) Cognitive-behavioral therapy for ADHD in

medication-treated adults with continued symptoms. Behav Res

Ther 43:831–842

ADHD: differences between responders

and nonresponders to stimulants

X. Carrasco1, V. Lopez1, D. Huerta1, P. Rothhammer1, F. Daiber1,J. Bustamante1, F. Zamorano1, H. Henrıquez1, E. Jeldres1,J.P. Figueroa1, K. Tirado1, K. Reinbach1, P. Perez1, M. Legue1,J. Lopez1, D. Cosmelli1, M. Devilat1, F. Rothhammer1, F. Aboitiz1

1Hospital Luis Calvo Mackenna, Universidad de Chile, Pontificia

Universidad Catolica de Chile, Santiago, Chile

Introduction: Not all ADHD subjects respond equally to stimulants

Methods: We analyzed the clinical response, CPT performance and

DAT1 polymorphism of 73 ADHD patients 8–14 years of age (13

girls) after 1 year of stimulant treatment.

Results: (1) A positive correlation between CPT performance and

clinical response; (2) clinical response depends on comorbidities while

CPT performance does not; (3) the clinically responding group shows a

higher IQ than the nonresponding group; (4) children displaying little

improvement in the CPT test after treatment have a higher frequency of

the DAT1 9R allele (v2 p 0.02); but clinical response is independent of

DAT1 polymorphism.

Conclusion: CPT and genetics are good predictors of stimulant response.

FONDECYT 1070761 and 1080219.

Efficacy of a psychoeducation intervention program

in families with ADD children and adolescents*

M.S. Centeno-Collado1, A.B. Ramırez-Gonzalez1, M. Ruiz-Veguilla1,M.D. Salcedo-Marın1, J.M. Granados-Moreno1,M.L. Barrigon-Estevez2, J.L. Rubio- Gomez1, M. Ferrin1,2

1Neurodevelopmental Psychiatry Research Unit (NPD), Jaen, Spain;2Institute of Psychiatry, London, UK, E-mail: [email protected]

*Preliminary results presented at the Eunethydis conference,

Winchester 2009


123

Introduction: Literature regarding efficacy of educational programs

in ADHD is scarce, with important methodological flaws [1–3].

Objectives: To evaluate clinical efficacy of a specific psychoeduca-

tional program on families with ADHD children/adolescents.

Methods: Double blind RCT; intervention-psychoeducation group

(n = 43), and active control-group (n = 37). Parents attended 12

weekly sessions, 90 min length in groups of 8–10 families and

received a structured-evidence-based psychoeducational program

(intervention), the controls attended supporting groups (active con-

trol). Families were evaluated after 6-month follow-up.

Results: Participant families did not differ in terms of age, gender,

diagnosis or comorbidities. Parents of ADHD children in the psy-

choeducation group presented improvement of ADHD symptoms

measured by Conners total scale and Conners index (p \ 0.028 and

0.001, respectively) and when compared to the control group

(ES = 0.60 and 0.89). Similar differences were found at 6-month

follow-up.

Conclusions: Psychoeducation intervention can be regarded as a good

alternative to standardized treatment on ADHD. Further studies are

required in order to disentangle which ADHD groups may be bene-

fited the most with this specific type of intervention.

References

1. Taylor E, Dopfner M, Sergeant J, Asherson P, Banaschewski T,

Buitelaar J et al (2004) European clinical guidelines for

hyperkinetic disorder – first upgrade. Eur Child Adolesc Psychi-

atry 13(Suppl 1):I7–I30

2. The MTA Cooperative Group (1999) Multimodal treatment study

of children with ADHD. a 14-month randomized clinical trial of

treatment strategies for attention-deficit/hyperactivity disorder.

Arch Gen Psychiatry 56(12):1073–1086

3. Montoya A, Colom F, Ferrin M (2010) Is psychoeducation for

children and adolescents with ADHD efficacious? A systematic

literature review (submitted)

Differential effects of methylphenidate and atomoxetine

in brain activation during a time discrimination task

in medication naıve children with ADHD

Ana Cubillo1, Anna Smith1, Nadia Barret1, Vincent Giampietro2,Eric Taylor1, Katya Rubia1

1Department of Child and Adolescent Psychiatry, Institute of

Psychiatry, King’s College, London, UK; 2Department of

Biostatistics, Institute of Psychiatry, King’s College, London, UK

Introduction and objective(s): Methylphenidate (MPH), a predom-

inant dopamine transporter blocker, enhances fronto-striatal

activation in ADHD during tasks of cognitive control and time esti-

mation [1, 2]. Atomoxetine (ATX), a predominant noradrenaline

transporter blocker, is used as an alternative treatment for ADHD.

However, no fMRI study has investigated its effects or compared its

effects on brain activation with that of Methylphenidate in ADHD.

Methods: After acute administration of MPH, ATX or placebo, eight

medication-naıve children with ADHD performed a time discrimi-

nation task in a double-blind randomized design. Within-group

repeated-measures ANOVA were conducted.

Results: ATX and MPH increased activation in anterior cingulate

during time estimation, but the effect was significantly stronger for

ATX over MPH. ATX only increased activation in the cerebellum.

Discussion: These preliminary results show that during time per-

ception, ATX has a shared, but more pronounced effect in ADHD

children on anterior cingulate activation and a drug-specific effect on

cerebellum activation.

Conclusion: ATX has stronger effects than MPH on anterior cingu-

late and cerebellum which is in line with the dense presence of

noradrenaline transporters in these regions [3].

References

1. Rubia K, Halari R, Christakou A, Taylor E (2009) Impulsiveness

as a timing disturbance: neurocognitive abnormalities in atten-

tion-deficit hyperactivity disorder during temporal processes and

normalization with methylphenidate. Philos Trans R Soc Lond B

Biol Sci 364:1919–1931

2. Vaidya CJ, Austin G, Kirkorian G, Ridlehuber HW, Desmond JE,

Glover GH, Gabrieli JDE (1998) Selective effects of methylpheni-

date in attention deficit hyperactivity disorder: a functional magnetic

resonance study. Proc Natl Acad Sci USA 95:14494–14499

3. Mazei MS, Pluto CP, Kirkbride B, Pehek EA (2002) Effects of

catecholamine uptake blockers in the caudate-putamen and

subregions of the medial prefrontal cortex of the rat. Brain Res

936:58–67

Supervision of the parent training observing

the evaluation of the behaviour at school in patients

affected by ADHD

F. D’Ambrosio1, R. Cascella1, L. Castaldo2, R. Maresca1,E. Sarnataro1, M. Marino1

1Neuropsychiatry Department, Second University of Naples, Naples,

Italy; 2Department of Pediatrics, University ‘‘Federico II’’, Naples,

Italy

Introduction and objective: For ADHD patients we organized ses-

sions of parent training. The aim of this study is monitoring the

efficacy of PT through the behavioural evaluation of ADHD-children,

at school.

Methods: We chose 36 couples of parents of 65 ADHD patients for a

program of PT (9 weekly individual meetings, 45-min long). All

received Conner’s teacher rating scales revised to be filled in by

teachers both during the diagnostic phase and after 6 months.

Results: The score obtained with CTRS-R during the diagnostic

phase was on average 73.66 (main score for patients out of PT was

74.24, main score for patients in PT was 75.41). After 6 months from

the diagnosis, the main score was 55.18 in patient processed in the

PT; while it was 59.44 in the other patients.

Discussion: in patients who had parents involved in the PT program,

after 6 months we noticed a most important improvement in the

behaviour of their children compared with the parents who were not

processed in PT.

Conclusion: We can state that the PT program improved the chil-

dren’s behaviour at school.


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A small-scale randomized controlled trial of the self-

help version of the new forest parent training

programme for children with ADHD

David Daley1, Michelle O’Brien1

1School of Psychology, Bangor University, Wales, UK

Introduction and objective(s): Despite the availability of effective

psychosocial interventions, the prevalence of ADHD creates a need

that far exceeds available personnel and resources. This study eval-

uates a self-help version of the new forest parent training programme

(NFPP-SH)

Methods: Forty-three parents of children aged 5–11 (mean

87 months) undergoing assessment for ADHD, were randomised to a

7 week self-help (N = 18) or waiting list control (N = 25) inter-

vention in this small trial. Measures were collected at baseline and

immediately after intervention.

Results: Self-help intervention was associated with significant

reductions in parent rated and clinical interview scores for ADHD

symptoms, and parental psychopathology, but not observed child

behaviour or parent–child interaction. Effect sizes were moderate but

clinical significant change scores were low.

Discussion: Self help intervention appears to offer a promising

alternative means of delivering parent training to reduce ADHD

symptoms, future studies should seek to investigate longer-term

outcomes, moderators of effect and combined medication manage-

ment and self-help intervention.

Conclusion: With the correct material parents can teach themselves

strategies to help their ADHD children.

References

1. Laver-Bradbury C, Weeks A, Thompson M, Daley D, Sonuga-

Barke EJS (2010) Step by step help for children with ADHD.

Jessica Kingsley, London

2. Sonuga-Barke EJS, Daley D, Thompson M, Laver-Bradbury C,

Weeks A (2001) Parent-based therapies for preschool attention-

deficit/hyperactivity disorder: a randomized, controlled trial with

a community sample. J Am Acad Child Adolesc Psychiatry

40:402–408

3. Thompson MJJ, Laver-Bradbury CL, Ayres M, Le Poidevin E,

Mead S, Dodds C, Psychogiou L, Bitsakou P, Daley D, Weeks A,

Miller-Brotman L, Abikoff H, Thompson P, Sonuga-Barke EJS

(2009) A small-scale randomized controlled trial of the revised

new forest parenting package for preschool children with

attention deficit hyperactivity disorder. Eur Child Adolesc


The effects of atomoxetine on cognitive control

in ADHD and RD

Christien de Jong1

1Department of Clinical Neuropsychology, VU University,


Objective: The effects of a promising pharmacological treatment for

attention-deficit hyperactivity disorder (ADHD), atomoxetine, were

studied on executive functions in both ADHD and reading disorder

(RD) since earlier research demonstrated an overlap in executive

functioning deficits in both disorders. In addition, the effects of ato-

moxetine were explored on lexical decision.

Methods: Sixteen children with ADHD, 20 children with

ADHD + RD, 21 children with RD and 26 normal controls were

enrolled in a randomized placebo-controlled cross-over study. Chil-

dren were measured on visuospatial working memory, inhibition and

lexical decision on the day of randomization and following two 28-

day medication periods.

Results: Children with ADHD + RD showed improved visuospatial

working memory performance and, to a lesser extent, improved

inhibition following atomoxetine treatment compared to placebo. No

differential effects of atomoxetine were found for lexical decision in

comparison to placebo. In addition, no effects of atomoxetine were

demonstrated in the ADHD and RD groups.

Conclusion: Atomoxetine improved visuospatial working memory

and to a lesser degree inhibition in children with ADHD + RD, which

suggest differential developmental pathways for comorbid

ADHD + RD as compared to ADHD and RD alone.

Keywords: Atomoxetine, ADHD, RD, Inhibition, Visuospatial

working memory

Assessment of medical treatment of adult ADHD

by repeated measures of ASRS in a prospective

observational clinical study

Mats Fredriksen1, Dawn E. Peleikis2

1Department of Psychiatry, Vestfold Mental Health Care Trust, 3103

Tønsberg, Norway; 2Department of Psychiatry, Oslo University

Hospital, Alna, 0585 Oslo, Norway

E-mail: [email protected]; [email protected]

Introduction and objective: This study explores the utility of the

Adult ADHD Self-Report Scale (ASRSv1.1) tracking outcome of

treatment with methylphenidate in medication naive adults with

ADHD [1]. In U.S. ASRSv1.1 has documented psychometric prop-

erties [2, 3].

Methods: Included patients are diagnosed according to the DSM-IV

criteria (N = 80), comorbidity examined by diagnostic interview

(M.I.N.I.). The outcome measured by changes in the ASRSv1.1

symptoms checklist, and compared with investigator’s assessment

(CGI), self-rating of symptom-checklist-90-revised (SCL-90-R), and

the Wender Utah rating scale (WURS); performed ANOVA statistics

(SPSS, v16.0).

Results: At baseline ASRSv1.1 sumscore correlated significant with

WURS25, and the general symptoms (GSI) of SCL-90R. Repeated

measurements demonstrated significant average reduction (39%) at

6 weeks sustaining at 3 months (p = 0.005) (effect size 0.72), as did

the ASRS-Screener, attained thresholds-values, constructs of atten-

tion-deficits and hyperactivity–impulsivity.

Discussion: ASRS is originally a screening-instrument, however in

our results scores correlated with other measures assessing outcome,

even subconstructs demonstrated change. Bias of self-ratings, repe-

ated performance and translation not cultural validated are discussed.

Conclusion: The ASRS-scores corresponded with other measures

of outcome, and demonstrated a significant improvement during

3-month treatment.

References

1. Murphy KR, Adler LA (2004) Assessing attention-deficit/

hyperactivity disorder in adults: focus on rating scales. J Clin

Psychiatry 65(Suppl 3):12–17

2. Kessler RC, Adler L, Ames M, Delmer O, Faraone S, Hiripi E,

Howes MJ, Jin R, Secnik K, Spencer T, Ustun TB, Walters EE

(2005) The World Health Organization Adult ADHD Self-Report


123

Scale (ASRS): a short screening scale for use in the general

population. Psychol Med 35:245–256

3. Kessler RC, Adler LA, Gruber MJ, Sarawate CA, Spencer T, Van

Brunt DL (2007) Validity of the World Health Organizational

adult ADHD self-report scale (ASRS) screener in a representative

sample of health plan members. Int J Methods Psychiatr Res

16:52–65

Methodological issues associated with clinical trials

in adult ADHD

A. Haege1, R.W. Dittmann1

1Research Unit for Paediatric Psychopharmacology, Department of

Child and Adolescent Psychiatry, Central Institute of Mental Health,

Medical Faculty Mannheim, University of Heidelberg, Heidelberg,

Germany

Objective: To review the literature with respect to relevant problems

and limitations of clinical trials in adult ADHD.

Methods: Systematic review of peer-reviewed and published double-

blind placebo-controlled medication trials in adult ADHD, with focus

on reported and discussed limitations.

Results: From 48 studies and 2 meta-analyses (1981–2009) most

commonly discussed limitations were: ‘‘too small samples’’ (n = 19;

40%) and possibly ‘‘too short period of treatment’’ (n = 19; 40%).

Also, authors reported issues such as ‘‘the exclusion of comorbidities’’

(n = 9; 19%), ‘‘self report only’’ (n = 9; 19%), ‘‘too low doses’’

(n = 8; 17%), ‘‘low percentage of enrolled patients from those

screened’’ (n = 8; 17%).

Discussion/conclusion: The observed limitations appear important

from both methodological and clinical perspectives. These issues

(apart from ‘‘comorbidities’’) will have impact on the assessments by

regulatory agencies during registration. In contrast, ‘‘feasibility’’

aspects have to be taken seriously, e.g., clinical reality, availability of

patients/study sites, time-lines, financial restrictions. The clinical

development for a certain compound, indication and specific patient

population will have to consider both perspectives.

Also, methodological limitations should be taken into account when

deriving recommendations/guidelines for the routine treatment of

broader patient populations.

References

1. Kolar et al (2008) Treatment of adults with attention-deficit/

hyperactivity disorder. Neuropsychiatr Dis Treat 4(2):389–403

2. Simpson et al (2004) Atomoxetine—a review of its use in adults

with attention deficit hyperactivity disorder. Drugs 64(2):206–

222

Any indication for bias due to participation?

Comparison of the effects of a parent management

training rated by participating and non-participating

parents

Christopher Hautmann1, Herbert Hoijtink2, Ilka Eichelberger1,Charlotte Hanisch3, Julia Pluck1, Daniel Walter1, Manfred Dopfner1


University of Cologne, Cologne, Germany; 2Department of

Methodology and Statistics, University of Utrecht, Utrecht, The

Netherlands; 3Department of Social Sciences, University of Applied

Sciences Dusseldorf, Dusseldorf, Germany

Introduction and objective: Effectiveness of a parent management

training for children with externalizing behavior problems was

investigated under routine care conditions. Current literature is lim-

ited by the fact that parents who rate the child behavior are in general

at the same also training participants. Their ratings might therefore be

biased. To investigate this in more detail in this secondary analysis

ratings of participating and non-participating parents were compared

with each other.

Methods: Fifty-six families were included in a within-subject control

group study. Training participants were predominately mothers, training

non-participants predominately fathers. In this design, a waiting period

prior to treatment served as the control condition for the treatment.

Results: For attention problems and conduct problems, a significant

decrease during the training period was found for both raters.

Moreover, no difference in magnitude for both raters were found.

Discussion: There is no indication that treatment effects are strongly

biased due to the participation in the training.

Conclusions: This is the first study that has investigated hints for a

participation bias. More research is needed by considering and con-

trasting additional perspectives.

TEAMS (training executive, affective and motor skills):

piloting a novel neurocognitive intervention

for hyperactive preschoolers

Dione M. Healey1, Jeffrey M. Halperin2

1University of Otago, Dunedin, New Zealand; 2Queens College of the

City University of New York, New York, USA

Introduction and objective: Psychopharmacologic and behavioural

treatments for ADHD provide external regulation of symptoms which

are highly effective during the active intervention phase, but gains are

rarely maintained after the termination of treatment. This study

assessed the effectiveness of a novel neurocognitive intervention for

hyperactive preschoolers focused on teaching internal self-regulatory

skills.

Methods: Twenty-four 3–4 years old with Hyperactivity T-scores of

65 or above on the BASC-2 participated. The intervention involved

weekly clinic-based sessions for 5 weeks. Children played the games

in one room and next-door parents were taught the games and how to

increase cognitive/behavioral demands as their child learned to master

the game. Parents were asked to spend at least 30 min per day playing

these games with their children.

Results: Paired samples t tests assessing pre- to post-intervention

differences revealed significant reductions in hyperactivity on the

BASC-2 and ADHD-RS, and improvements in neuropsychological

functioning on the NEPSY Visuomotor Precision and Stanford Binet

Working Memory subtests.

Conclusions: Preliminary data indicate that a structured play-based

approach to neurocognitive training may be an effective treatment

option for hyperactive preschoolers.

References

1. Conners CK (2002) Fourty years of methylphenidate treatment in

attention-deficit/hyperactivity disorder. J Atten Disord 6(Suppl

1):S17–S30

2. Mannuzza S, Klein RG, Moulton JL (2003) Persistence of

attention-deficit/hyperactivity disorder into adulthood: what have

we learned from the prospective follow-up studies? J Atten

Disord 7:93–100


123

3. Pelham WE, Fabiano GA (2008) Evidence-based psychosocial

treatments for attention/deficit-hyperactivity disorder. J Clin

Child Adolesc Psychol 37:184–214

Effects of working memory training on medicated

ADHD preadolescents (10–12 years)

Kjell Tore Hovik1, Anne-Kristine Aarlien1, Brit-Kari Saunes2,Jens Egeland1

1Vestfold Mental Health Care Trust, Tønsberg, Norway; 2Telemark

Hospital, Skien, Norway

Objective: PC-based working memory (WM) training has shown

improved cognitive performance and symptom reduction in unmedi-

cated ADHD youth [2, 3]. The present study tests whether also

medicated preadolescents profit from WM training and whether

training effects transfer to math and reading abilities [1].

Method: Seventy 10–12-year-olds with ADHD are taking part in the

ongoing study. All subjects receive treatment-as-usual and are ran-

domly assigned to either 5-week PC training or control group.

Testing/symptom ratings from teachers/parents are carried out pre/

post intervention and after 6 months.

Results: Analysis of the first 33 cases completing first post-test

showed no differential effect in the intervention group on any of the

neuropsychological tests or teacher ratings. Parent ratings showed

decrease in ADHD symptoms. Differential improvements were also

registered for reading/math scores.

Conclusion: Medication could have exhausted the possibility of

additional training effect. Additionally, it is not clear whether the

progress can be ascribed to the WM training or placebo. Hopefully,

data from the 6-month post-test will help clarify this issue. Pre-

liminary hypotheses will be presented in the poster.

References

1. Holmes J, Gathercole SE, Dunning DL (2009) Adaptive training

leads to sustained enhancement of poor working memory in

children. Dev Sci 12:F9–F15

2. Klingberg T, Forssberg H, Westerberg H (2002) Training of

working memory in children with ADHD. J Clin Exp Neuropsy-

chol 24:781–791

3. Klingberg T, Fernell E, Olesen P, Johnson M, Gustafsson P,

Dahlstrom K, Gillberg CG, Forssberg H, Westerberg H (2005)

Computerized training of working memory in children with

ADHD—a randomized, controlled trial. J Am Acad Child

Adolesc Psychiatry 44:177–186

Guided parental self-help for parents of children

with externalizing problem behaviour: results of two

pilot studies and plan of an effectiveness study

Josepha Katzmann1, Christopher Hautmann1, Frauke Kierfeld1,Laura Mokros1, Anna Mutsch1, Sara Scharmanski1, Kristin Schwarz1,Manfred Dopfner1

1University of Cologne, Cologne, Germany

Introduction and objective: In two pilot studies the efficacy of

guided parental self-help (GPSH) for parents of children with exter-

nalizing problem behaviour was investigated. In both studies parents

worked through the self-help book ‘‘Wackelpeter und Trotzkopf’’ [1]

and additionally received a weekly counselling telephone call.

Method: In the first study 21 parents of 6–15-year-old children with

ADHD and/or ODD symptoms were investigated in a one-group pre-

post design. In the second pilot study 26 families of preschool children

with disruptive behaviour disorders were compared with 22 families of

a non-treated waiting list control group. In the second study long-term

effects were additionally investigated in a 1-year follow-up.

Results: In both studies a symptom reduction with moderate to large

effect sizes concerning ADHD and ODD symptoms, externalising and

internalising problems was found. In the second study most of the

effects were stable at a 1-year follow-up.

Discussion: GPSH may be a good alternative for parents of children

with disruptive behaviour problems without access to or time for

traditional psychotherapy.

Conclusion: Preliminary findings are promising. Yet, more research

is needed before providing GPSH for parents of children with

externalizing problem behaviour in a broader context. For this reason

a further effectiveness trial is planned.

Reference

1. Dopfner M, Schurmann S, Lehmkuhl G (2006) Wackelpeter und

Trotzkopf: Hilfen fur Eltern bei hyperkinetischem und opposit-

ionellem Verhalten (Wackelpeter and Trotzkopf: help for parents

of children with hyperkinetic and oppositional behavior), 3rd edn.

Beltz Psychologie Verlags Union, Weinheim

Preliminary tomographic neurofeedback results

from children with ADHD

M. Liechti1,2, S. Maurizio1, H. Heinrich3,4, G. Thalmann1, L. Meier1,Y. Schwitter1, M. Hartmann1, S. Walitza1, H.-C. Steinhausen1,L. Jancke2, R. Drechsler1, D. Brandeis1,5,6



Institute for Psychology, University of Zurich, Zurich, Switzerland;3Department of Child and Adolescent Psychiatry, University of

Erlangen-Nurnberg, Nuremberg, Germany; 4Heckscher-Klinikum,

Munich, Germany; 5Department of Child and Adolescent Psychiatry

and Psychotherapy, Central Institute of Mental Health, Mannheim,

Germany; 6Center for Integrative Human Physiology, University of

Zurich, Zurich, Switzerland; E-mail: [email protected]

Introduction and objectives: In an ongoing study, tomographic

neurofeedback (NFB) is evaluated to improve treatment of attention

deficit hyperactivity disorder (ADHD). We hypothesised that region

specific NFB training leads to a continuous normalisation of theta/

beta ratios.

Methods: Five children with ADHD, aged 10–13 years, were trained

over 18 sessions to regulate their theta/beta-frequencies and slow

cortical potentials in the anterior cingulate cortex (ACC). Thirty-one-

channel electroencephalogram (EEG) was used to calculate low-res-

olution electromagnetic tomographic (sLORETA) NFB. Spectral

power of baseline resting EEG was analysed in different frequency

bands.

Results: Preliminary analysis showed a decrease of theta/beta ratios

in the ACC across training sessions. Linear regression was significant

for the group mean, and individual regression slopes tended to be

negative across subjects. According to parents’ ratings, ADHD

symptoms were significantly improved after training.

Discussion and conclusions: These results indicate that tomographic

NFB training can lead to a continuous decrease of initially elevated


123

theta/beta-ratios, reflecting an increasingly attentive resting EEG in

the target region ACC, together with clinical improvements. These

results suggest that NFB helps normalising EEG activity in a specific

brain region affected in ADHD.

Supported by the SBF COST B27 ENOC and by a Grant to the GD of

the Kanton of Zurich

Keywords: Attention deficit hyperactivity disorder (ADHD), Tomo-

graphic neurofeedback, Resting electroencephalogram (EEG),

Frequency bands, Theta/beta

Effects of tomographic neurofeedback training on error

processing in children with ADHD

L. Meier1, M. Liechti1,2, S. Maurizio1, H. Heinrich3,4, G. Thalmann1,Y. Schwitter1, M. Machler1, S. Walitza1, H.C. Steinhausen1,L. Jancke2, R. Drechsler1, D. Brandeis1,5,6



Institute for Psychology, University of Zurich, Zurich, Switzerland;3Department of Child and Adolescent Psychiatry, University of

Erlangen-Nurnberg, Nuremberg, Germany; 4Heckscher-Klinikum,

Munich, Germany; 5Department of Child and Adolescent Psychiatry

and Psychotherapy, Central Institute of Mental Health, Mannheim,

Germany; 6Center for Integrative Human Physiology, University of

Zurich, Zurich, Switzerland

Introduction and objectives: Attention-deficit/hyperactivity disorder

(ADHD) has repeatedly been associated with dysfunctions in fronto-

striatal networks involved in attention, response control and error

processing. The aim of the current study is to investigate whether

tomographic neurofeedback training has an impact on these physio-

logical dysfunctions in ADHD associated with error-processing.

Methods: Error processing measured by behavioral and electrophys-

iological parameters during an error related negativity flanker task was

examined in children with ADHD combined type according to DSM-

IV (n = 13) before and after tomographic neurofeedback training.

Results: Preliminary results indicated that after tomographic neuro-

feedback training, children with ADHD displayed unchanged

frontocentral error related negativity (ERN), while some changes were

observed in the subsequent time windows including the error positivity.

Discussion and conclusion: The lack of ERN changes suggests

considerable stability over tests repetitions. Whether the changes in

subsequent physiological markers of error processing are associated

with behavioral improvement after neurofeedback training is cur-

rently being further investigated.

Keywords: Attention deficit hyperactivity disorder (ADHD), Event-

related potentials, Error-related negativity, Error-related positivity,

Tomographic neurofeedback

The effects of a short in-service training on teaching

students with ADHD-symptoms: teacher’s experiences

and the behavior management techniques used. A pilot

study

Vesa Narhi1

1Niilo Maki Institute; Jyvaskyla, Finland

Introduction and objective: ADHD-symptoms cause a risk for

school failure for the child, for the teachers they increase the need of

behavior management and risk for work related stress. Teachers lack

training on effective school interventions and applicable and inex-

pensive forms of support for teachers are needed [1].

Methods: Eighty teachers participated the 2-day training in two

groups. The first day provided the basics of school interventions and

instructions for teachers to apply them. The teachers conducted and

reported an intervention for their pupil. After 2 months at the second

day, the interventions conducted were discussed and evaluated.

Questionnaires were used twice before and after the training.

Results: Pre- and post-training measures will be compared. Pre-

training data indicated that the scale reliabilities were acceptable.

Discussion: The effects of short training and the possibilities to

support teachers with such will be discussed.

Conclusions: Little is known about the efficacy of different ways to

support teachers in conducting classroom interventions for students

with ADHD-symptoms. It’s likely that short, inexpensive training will

meet the needs of some, but not all, teachers.

Reference

1. DuPaul GJ, Eckert TL (1997) The effects of school-based

interventions for attention deficit hyperactivity disorder: a meta-

analysis. School Psychol Rev 26:5–27

Dialectical behavioral therapy-based treatment in Adult

ADHD

Alexandra Philipsen, Erika Graf, Swantje Matthies, Patricia Borel,Michael Colla, Esther Sobanski, Barbara Alm, Christian Jacob,Michael Rosler, Bernhard Kis, Michael Huss, Klaus Lieb,Ludger Tebartz van Elst, Evgeniy Perlov, Jochen Kotting,Mathias Berger

Adult ADHD is a risk factor for co-occurring disorders and negative

psychosocial consequences. Given this background there is a need for

effective psychotherapeutic treatments for adults with ADHD. Due to

overlapping clinical features in adult ADHD and borderline person-

ality disorder our treatment is mainly based on the principles of

dialectical behavioral treatment. Cognitive behavioral treatment

strategies are mainly integrated to modify maladaptive thoughts

interfering with therapy. The structured program is applied in weekly

session to adult ADHD outpatients in a group setting. As shown in our

pilot study and feasibility multicenter trial, the DBT-based program

resulted in good outcomes. ADHD severity, depression and personal

health status were significantly improved. Patients regarded the pro-

gram topics ‘‘behavioural analyses’’, ‘‘mindfulness’’ and ‘‘emotion

regulation’’ as the most helpful. However, so far, randomized pla-

cebo-controlled studies comparing the effects of medical

management, disorder-oriented psychotherapy, and the combination

of both are still lacking. Therefore, the University Freiburg has ini-

tiated a multicenter trial at eight university sites which is funded by

the German Federal Ministry of Research and Education

(01GV0606). Preliminary data of this study will be presented.

A treatment programme for preschool children

with ADHD characteristics

Anna M. Re1, Cesare Cornoldi2

1Developmental Psychology Department, University of Padova,

Padua, Italy; 2General Psychology Department, University of Padova,

Padua, Italy


123

Diagnosis and treatment of ADHD usually take place at school age,

when a child may already have had negative experiences. Then early

diagnosis and psychological intervention in pre-school years are

important [3]. In the present study children with ADHD characteris-

tics were selected by teachers on the basis of a teacher rating scale

(IPDDAI, [2]). This at-risk group participated in a 12-week pro-

gramme [1] designed to promote development of self-regulated

strategies while a matched control group performing normal activities

proposed by their teachers. Before treatment both groups performed a

visual-spatial working memory task (WM) as measure of information

maintenance and inhibition of irrelevant information. General

improvement was found after the training for all children, but this

change was more marked in the at-risk group, who showed a clear

increase in correct responses and made fewer errors on the WM task

than controls. Our findings suggest that early identification and

intervention appears to be very beneficial for such children. Further

attention should be devoted to early intervention with children at risk

of ADHD.

References

1. Caponi B, Clama L, Re AM, Cornoldi C (2009) Sviluppare la

concentrazione e l’autoregolazione, vol 3: Giochi e attivita sul

controllo della memoria di lavoro. Erickson, Trento

2. Marcotto E, Paltenghi B, Cornoldi C (2002). La scala IPDDAI:

contributo per la costruzione di uno strumento per l’identificaz-

ione precoce del DDAI. (The IPDDAI Scale: contribution to

building an instrument for early identification of ADHD).

Difficolta di Apprendimento 8:153–172

3. Sonuga-Barke EJS, Daley D, Thompson M, Laver-Bradbury C,

Weeks A (2001) Parent-based therapies for preschool attention-

deficit / hyperactivity disorder: a randomized, controlled trial

with a community sample. J Am Acad Child Adolesc Psychiatry

40(4):402–408

Micronutrients revisited: is there a role

for micronutrients in the treatment of ADHD afterall?

Julia J. Rucklidge1, J. Johnstone1, R. Harrison1, M. Taylor1,K. Whitehead1, I. Shaw1, R. Hughes1

1Department of Psychology, University of Canterbury, Private Bag

4800, Christchurch, New Zealand

Introduction and objective: To investigate the impact of a 36-

ingredient micronutrient formula consisting mainly of minerals and

vitamins on adults with ADHD and severe mood dysregulation

(SMD).

Method: Fourteen medication-free adults with ADHD and SMD

completed an 8-week open-label trial; pre and post measures of

psychiatric symptoms and tests of processing speed, memory and

executive functioning were conducted. A matched control group of 14

nonADHD adults not taking the formula were assessed on the same

neurocognitive tests 8 weeks apart in order to estimate the impact of

practice effects.

Results: Side effects were transitory and mild. Significant improve-

ments were noted across informants (self, observer, clinician) on

measures of inattention and hyperactivity/impulsivity, mood, quality

of life, anxiety, and stress all with medium to very large effect sizes.

Significant improvement was also observed in the ADHD group, but

not the control group, across a range of verbal abilities including

verbal learning, verbal cognitive flexibility and fluency, and verbal

inhibition.

Conclusions: Micronutrients remain an intriguing and yet under-

studied option for the treatment of mental illness. Possible

mechanisms of action will also be discussed.

E-mail: [email protected]

Psychological ADHD treatment: influence on cognitive

networks

Michael Siniatchkin1, Alexander Prehn-Kristensen2, Silja Knoechel2,Ulrich Stephani1, Gabriella Gerber-von Mueller3,Wolf-Dieter Gerber3

1University Hospital of Pediatric Neurology, Christian-Albrechts-

University of Kiel, Kiel, Germany; 2Clinic for Child and Adolescent

Psychiatry, Christian-Albrechts-University of Kiel, Kiel, Germany;3Institute of Medical Psychology, Christian-Albrechts-University of

Kiel, Kiel, Germany

Introduction and objectives: Response cost and token approach

(RCT) is an effective treatment program for ADHD [1]. It can be

suggested that the RCT summer camp training exerts an influence on

neuronal networks responsible for impulse control.

Methods: Functional MRI was performed before and after a RCT

summer camp training (elements of social skill training, attention

training and sports) in ten children with ADHD. Ten healthy children

were investigated twice to exclude the repetition effect. For fMRI (3-

Tesla Philips Achieva scanner, TR = 2,250 ms, 30 slices, 64 9 64

matrix, slice thickness 3.5 mm, FOV 200 mm, flip angle 90�), a

classical Go-NoGo paradigm was used.

Results: The RTC training caused a pronounced reduction of the

response variability (p \ 0.01). In the ADHD group, NoGo condition

revealed a weak activation in the anterior cingulate before the training

This activation was significantly more pronounced after the training.

The repetition effects were not observed in healthy children.

Discussion and conclusions: Children with ADHD learned more

cognitive control in a continuous performance task as revealed by

both neuropsychological outcome and fMRI.

References

1. Gerber-von Muller G, Petermann U, Petermann F, Niederberger

U, Stephani U, Siniatchkin M, Gerber WD (2009) Das ADHS-

Summercamp—Entwicklung und Evaluation eines multimodalen

Programms’, Kindheit und Entwicklung, vol 18, pp 162–172

Neurofeedback in children with attention-deficit/

hyperactivity disorder (ADHD): design and methods

of a controlled multicenter study

Sabina Steiner1, Sonja Kaller2, Ute Strehl2, Daniel Wachtlin3,Daniel Brandeis1, Tobias Banaschewski1, Martin Holtmann4


Central Institute of Mental Health, Mannheim, Germany; 2Institute of

Medical Psychology and Behavioral Neurobiology, Eberhard-Karls-

University, Tubingen, Germany; 3Interdisciplinary Centre Clinical

Trials, Mainz, Germany; 4LWL-Hospital for Child and Adolescent

Psychiatry, Ruhr-University Bochum, Bochum, Germany

Introduction: Neurofeedback as an additional/alternative treatment

ADHD is based on neurophysiological changes characteristic of


123

ADHD children [1]. Recent studies provided evidence for these

specific neurophysiological effects: normalisation of the contingent

negative variation (CNV) and of the frontal NoGo N2 [1, 2].

Methods: One-hundred forty-four patients will be randomly assigned

to 25 training sessions over 3 months in a randomised controlled trial

(RCT) with slow cortical potentials versus electromyographic feed-

back. EMG feedback was chosen as the control condition to ensure an

equal amount of reinforcement, time, and interaction, guaranteed by

completely identical devices for EEG- and EMG-feedback.

Results: The primary endpoint of the trial is the change of the SNAP-

IV after the 3-month treatment and one additional month washout of

medication.

Discussion: The implementation of a control condition for NF is

difficult, but the design of the ongoing RCT surmounts many disad-

vantages of previous studies in that it provides a randomized

controlled design, a large sample size, and representative sampling.

Conclusion: Results of this RCT provide indication for a better

understanding whether effects of neurofeedback are caused specifi-

cally by this intervention.

References

1. Holtmann M, Stadler C (2006) Electroencephalographic-biofeed-

back fort he treatment of attention-deficit/hyperactivity disorder

in childhood and adolescence. Expert Rev Neurother 6(4):533–

540

2. Heinrich H, Gevensleben H, Freisleder FJ, Moll GH, Rothen-

berger A (2003) Training if slow cortical potentials in attention-

deficit/hyperactivity disorder: evidence for positive behavioural

and neurophysiological effects. Biol Psychiatry 55:772–775

Social-skills training and parental training plus

standard treatment versus standard treatment

of children with attention-deficit hyperactivity disorder:

the SOSTRA randomised trial protocol

Ole Jakob Storebø1,2,3,6, Jesper Pedersen1, Maria Skoog3,Per Hove Thomsen4,7, Christian Gluud3,5, Erik Simonsen2,6

1Child Psychiatric Daytime Unit, Child and Adolescent Psychiatric

Centre, Region Zealand, Holbaek, Denmark; 2Psychiatric Research

Unit, Region Zealand, Roskilde, Denmark; 3Copenhagen Trial Unit,

Centre for Clinical Intervention Research, Department 3344,

Rigshospitalet, Copenhagen University Hospital, Copenhagen,

Denmark; 4Psychiatric Hospital for Children and Adolescents,

Risskov, Denmark; 5Cochrane Hepato-Biliary Group, Copenhagen

Trial Unit, Centre for Clinical Intervention Research, Department

3344, Rigshospitalet, Copenhagen University Hospital, Copenhagen,

Denmark; 6Faculty of Health Sciences, University of Copenhagen,

Copenhagen, Denmark; 7Aarhus Universitet, Arhus, Denmark

Introduction: Many children with ADHD have difficulties with

social interaction [1]. Several randomised clinical trials suggest that

social-skills training helps children with ADHD [2]. Some studies

have shown a connection between ADHD and disorganised attach-

ment [3].

Objectives: The primary aim of the SOSTRA trial is to examine the

effect of the combination of social-skills training, parental training

plus standard treatment versus standard treatment alone in ADHD

patients; and secondary, to examine differences in the effect of the

treatment in relation to the children’s different attachment

competences.

Methods: The trial is constructed as a randomised two-armed, par-

allel group, assessor-blinded trial. The children will be examined at

baseline and after 3 and 6 months. There will be four identical 8-week

treatment programs with 12–16 participants from 8 to 12 years per

program.

Discussion: The results from this trial could greatly benefit children

with ADHD because social-skills training may have a greater general

effect on social and emotional competences than does standard

treatment. Other strengths of this trial are the measurement of

attachment styles in children with ADHD and the comparison

between the effect of the social skills training and the attachment

competences.

References

1. Whalen CK, Henker B (1985) The social worlds of hyperactive

(ADHD) children. Clin Psychol Rev 5:447–478

2. Pfiffner LJ, McBurnet K (1997) Social skills training with parent

generalization: treatment effects for children with attention deficit

disorder. J Consult Clin Psychol 65:749–757

3. Punto C, Turton P, Hughes P, White S, Gillberg C (2006) ADHD

and infant disorganized attachment—a prospective study of

children next-born after stillbirth. J Atten Disord 10:83–91

Effects of methylphenidate on problem solving in adults

with attention deficit hyperactivity disorder

Lara Tucha1, Klaus W. Lange2, Thomas A. Sontag2,Anselm Furmaier1, Rainer Laufkotter3, Susanne Walitza4,Oliver Tucha1

1Department of Clinical and Developmental Neuropsychology,


of Experimental Psychology, University of Regensburg, Regensburg,

Germany; 3Department of Psychiatry, University of Regensburg,

Regensburg, Germany; 4Department of Child and Adolescent

Psychiatry, University of Zurich, Zurich, Switzerland

Introduction and objective: It has been shown that adults with

attention deficit hyperactivity disorder (ADHD) suffer from a variety

of cognitive disturbances including impairments of executive func-

tioning. Two studies were performed to assess both divergent and

convergent thinking as aspects of problem solving in adults with

ADHD.

Methods: The first study compared the problem solving abilities of

healthy participants and unmedicated adults with ADHD. In the

second study, problem solving abilities of adults with diagnosed

ADHD were examined twice, i.e. on and off methylphenidate (MPH),

and compared with the performance of a healthy control group.

Convergent thinking was measured using a transformation task, while

divergent thinking was assessed using fluency tasks.

Results: Adults with ADHD off MPH displayed marked deficits of

both divergent and convergent thinking. MPH treatment resulted in a

marked improvement of convergent thinking, while no effect of

medication was found regarding divergent thinking.

Discussion: Pharmacological treatment of adults with ADHD

revealed a differential effect of MPH on problem solving abilities.

Conclusion: Psycho-educational intervention or executive training

programmes should be considered in the treatment of adult ADHD.


123

Poster Abstracts: F Treatment

Maternal exposure to atomoxetine alters gene

expression in the fetal brain

P.T. Udvardi1,2, U. Schaz2, S. Liebau2, J. Kuster1, J.M. Fegert1,T.M. Bockers2, A.G. Ludolph1,2

1Department of Child and Adolescent Psychiatry, University of Ulm,

Ulm, Germany; 2Institute of Anatomy and Cell Biology, University of

Ulm, Ulm, Germany

Objective: The efficacy and safety of atomoxetine, the only licensed

non-stimulant pharmacological treatment option for ADHD in Eur-

ope, is well investigated in clinical trials, the long-term effects in the

developing brain still remain elusive. In vitro studies prove that

besides the well-known inhibition of the norepinephrine transporter

(NET) atomoxetine acts as a blocker of the N-methyl-D-aspartate

(NMDA) receptor. Here we present an in vivo study carried out to

investigate atomoxetine’s effect in the maturing rat brain.

Methods: Pregnant Crl:SD(CD) rats were treated with atomoxetine

(3 mg/kg, i.p.) and sodium chloride (0.9%, i.p.), for the period

equivalent to human second to third trimenon of pregnancy. After the

end of treatment hippocampus, prefrontal cortex, mesencephalon and

striatum from embryos and dams were isolated for analysis of gene

expression.

Results: Quantitative real-time polymerase chain reaction (qRT-PCR)

analysis revealed altered expression of genes of the monoaminergic

and glutamatergic system in both embryos and dams.

Discussion: This study gives hints that atomoxetine might alter

transcriptional regulation of genes of the monoaminergic and gluta-

matergic system in an age-dependent manner.

Conclusion: Atomoxetine alters gene expression in vivo.

Keywords: ADHD, Atomoxetine, In vivo, Gene expression, NMDA

Trends in incidence, usage patterns and characteristics

of children, adolescents and adults initiating immediate-

or extended-release methylphenidate or atomoxetine

in The Netherlands during 2001–2006

Els van den Ban1,5, Patrick C. Souverein2, Hanna Swaab3,Herman van Engeland5, Eibert R. Heerdink2,4, Toine C.G. Egberts2,4

1Division Youth, Altrecht, Institute for Mental Health Utrecht,

Utrecht, The Netherlands; 2Division of Pharmacoepidemiology and

Pharmacotherapy Utrecht Institute for Pharmaceutical Sciences,

Faculty of Science, Utrecht University, Utrecht, The Netherlands;3Department of Clinical Child and Adolescent Studies, University of

Leiden, Leiden, The Netherlands; 4Department of Clinical Pharmacy,

University Medical Centre Utrecht, Utrecht, The Netherlands;5Department of Child and Adolescent Psychiatry, University Medical

Centre Utrecht, Utrecht, The Netherlands

Introduction and objectives: Previous Dutch studies showed

increasing psychostimulant use between 1995 and 2003. In 2003

methylphenidate extended-release and in 2005 atomoxetine were

introduced. To describe change in incidence of ADHD drugs, pre-

scription profiles and changes in usage patterns of patients\45 years

between 2001 and 2006.

Methods: Data (age, gender, drug information and dispensing infor-

mation) were obtained from Dutch community pharmacies as

collected by the Foundation for Pharmaceutical Statistics, covering

97% of all dispenses for prescription medicines to outpatients in The

Netherlands.

Results: Overall incidence of ADHD drugs use increased 6.5-fold

from 2001 to 2006 in men as well as in women. Absolute incidence

was highest among 6–11-year-old boys. Atomoxetine was prescribed

more often to patients with prior psychopharmacological treatment.

Persistence of ADHD drug treatment 1 year after initiation (i.e.

including continuation, switching and addition) increased over the

three time cohorts.

Conclusion: An increase in incidence in use of ADHD drugs between

2001 and 2006. Atomoxetine was channelled into a psychopharma-

cologically polluted population, reflecting different treatment needs.

Persistence of any ADHD drug treatment increased due to the

availability of more treatment options.

References

1. van den Ban E, Souverein P, Swaab H, van Engeland H,

Heerdink R, Egberts T (2010) Trends in incidence and charac-

teristics of children, adolescents, and adults initiating immediate-

or extended-release methylphenidate or atomoxetine in The

Netherlands during 2001–2006. J Child Adolesc Psychopharma-

col 20(1):55–61

Prepotent response inhibition predicts treatment

outcome in attention deficit hyperactivity disorder

S. van der Oord1, H.M. Geurts2, P.J.M. Prins1, P.M.G. Emmelkamp1,J. Oosterlaan3

1Department of Clinical Psychology, University of Amsterdam,

Amsterdam, The Netherlands; 2Department of Psychonomics,

University of Amsterdam, Amsterdam, The Netherlands;3Department of Clinical Neuropsychology, VU University


Introduction: Inhibition deficits, including deficits in prepotent

response inhibition and interference control, are core deficits in

ADHD. The predictive value of prepotent response inhibition and

interference control was assessed for outcome in a 10-week treatment

trial with methylphenidate [1].

Methods: Fifty children with ADHD (ages 8–12) received 10 weeks

of methylphenidate treatment. At pre-test prepotent response inhibi-

tion was assessed using the Stop-signal Task, interference control was

assessed using the Stroop Color-Word task. Methylphenidate was

individually titrated to an optimal dose. Treatment outcome was

assessed by parent- and teacher-rated ADHD behavior.

Results: Only stop-signal reaction time of the stop-signal task was a

significant predictor of parent-rated levels of inattention and hyper-

activity/impulsivity at outcome. Children with lower levels of

inhibition showed worse outcome after 10 weeks of treatment, inde-

pendent of medication dose.

Conclusion: Low levels of prepotent response inhibition are associ-

ated with worse response to treatment with methylphenidate.

Discussion: Prepotent response inhibition may be a specific inter-

mediate phenotypical predictor of treatment outcome.

Reference

1. Van der Oord S, Prins PJM, Oosterlaan J and Emmelkamp

PMG (2007) Does brief, clinically based, intensive multi-

modal behavior therapy enhance the effects of methyl-

phenidate in children with ADHD? Eur Child Adolesc



123

Response to methylphenidate treatment among adults

with ADHD according to comorbidity status

Marcelo M. Victor1, Eugenio H. Grevet1, Carlos A. I. Salgado1,Katiane L. Silva1, Paula Guimaraes1, Rafael G. Karam1,Eduardo S. Vitola1, Felipe A. Picon1, Veronica Contini3,Luis A. P. Rohde2; Paulo Belmonte-de-Abreu1,2, Claiton H. D. Bau1,3

1Adult ADHD Outpatient Clinic, Hospital de Clınicas de Porto

Alegre, HCPA, Porto Alegre, RS, Brazil; 2Department of Psychiatry,

Faculty of Medicine, Federal University of Rio Grande do Sul,

UFRGS, Porto Alegre, RS, Brazil; 3Department of Genetics, Institute

of Biosciences, Federal University of Rio Grande do Sul, UFRGS,

Porto Alegre, RS, Brazil

Introduction and objective: The evaluation of methylphenidate

(MPH) response in patients with ADHD has rarely evaluated the

effect of comorbidities [1]. The aim of this study is to evaluate

response to MPH in patients with ADHD and comorbid disorders.

Methods: Sociodemographic variables, comorbidity status and

response to MPH were evaluated in 164 patients with ADHD. The

analyses were restricted to subjects whose comorbidities did not

demand specific treatment before the use of MPH.

Results: The diagnosis of current oppositional defiant disorder (ODD)

was associated to a larger decrease in inattention (p = 0.05), hyper-

activity (p = 0.006) and ODD SNAP scores (p \ 0.001) following

MPH. After adjustment for basal scores, the only dimension that

remained significant was SNAP ODD (p = 0.05). Other comorbidi-

ties did not present significant effects.

Discussion: Overall, the presence of comorbidities does not have a

major influence in response to MPH. However, patients with current

ODD have a larger decrease in SNAP scores, especially in ODD

scores. This effect is mainly explained by pre-treatment severity.

Conclusions: These results reinforce the evidence suggesting that

MPH may be effective in ODD treatment.

Reference

1. Victor MM, Grevet EH, Salgado CA, Silva KL, Sousa NO,

Karam RG, Vitola ES, Picon FA, Zeni GD, Contini V, Rohde

LA, Belmonte-de-Abreu P, Bau CH (2009) Reasons for pretreat-

ment attrition and dropout from methylphenidate in adults with

attention-deficit/hyperactivity disorder: the role of comorbidities.

J Clin Psychopharmacol 29(6):614–616

Poster Sessions G: Emotional Factors

The effects of lisdexamfetamine dimesylate

on emotional lability in children aged 6–12 years

with attention-deficit/hyperactivity disorder

in a double-blind, placebo-controlled trial

Ann C. Childress1, Valerie Arnold2, Ben Adeyi3, Bryan Dirks3,Thomas Babcock3, Brian Scheckner3, Robert Lasser3,Frank A. Lopez4

1Center for Psychiatry and Behavioral Medicine, Las Vegas, NV,

USA; 2CNS Healthcare, University of Tennessee, Memphis, TN,

USA; 3Shire Development Inc., Wayne, PA, USA; 4Children’s

Developmental Center, Winter Park, FL, USA

Objective: To evaluate effects of lisdexamfetamine dimesylate

(LDX; Vyvanse�, trade name in US), a long-acting prodrug stimulant,

on emotional lability (EL) in children (6–12 years) with ADHD.

Methods: Post hoc analysis from a 4-week, randomised, double-

blind, placebo-controlled trial of LDX in children with ADHD

stratified subjects as with or without prominent baseline EL [score B3

or [3 on Conners’ Parent Rating Scale (CPRS) items: anger, loss of

temper, and irritability]. Efficacy was assessed relative to baseline at

endpoint and across the day in CPRS-EL scores (10:00, 14:00, and

18:00 h) and ADHD Rating Scale IV (ADHD-RS-IV) scores at

endpoint. Safety measures included treatment-emergent adverse

events (TEAEs).

Results: LDX showed improvement versus placebo (p \ 0.0005) for

EL items LS mean change scores at endpoint and throughout the day.

At endpoint, ADHD-RS-IV total, inattentive, and hyperactivity/

impulsivity scores decreased with LDX regardless of baseline EL.

TEAEs included decreased appetite, insomnia, upper abdominal pain,

headache, and irritability.

Discussion/conclusions: LDX improved EL and ADHD symptoms

regardless of baseline EL symptom severity. LDX demonstrated a

safety profile consistent with long-acting stimulants.


References

1. Biederman J, Krishnan S, Zhang Y, McGough JJ, Findling RL

(2007) Efficacy and tolerability of lisdexamfetamine dimesylate

(NRP-104) in children with attention-deficit/hyperactivity disor-

der: a phase III, multicenter, randomized, double-blind, forced-

dose, parallel-group study. Clin Ther 29:450–463

2. Strine TW, Lesesne CA, Okoro CA et al (2006) Emotional and

behavioral difficulties and impairments in everyday functioning

among children with a history of attention-deficit/hyperactivity

disorder. Prev Chronic Dis 3:A52

Electrophysiological correlates of emotion processing

in children with ADHD

Georgia Chronaki1, Matthew Garner1, Julie Hadwin1,Margaret Thompson1, Edmund Sonuga-Barke1, Samantha Broyd1

1School of Psychology, University of Southampton, Southampton,

UK

Research suggests that inaccurate perception of emotion from non

verbal cues might underlie social skills difficulties in children with

behaviour problems (Cadesky et al. 2000). Thus far, one ERP

study has been conducted on emotion processing in adolescents

with hyperactivity (Williams et al. 2008). Forty-one 6–11-year-old

children from the community with different levels of externalizing

symptoms participated in this study. Children performed a facial

and vocal emotion recognition task whilst EEG was recorded from

19 channels. After controlling for child age, child hyperactivity

was negatively associated with accuracy to perceive happy faces

(r = -0.38, p = 0.022). Results revealed that the angry versus

neutral (but not angry vs. happy) difference in all three Slow

Waves amplitude was larger in central than parietal areas

[F(1,34) = 10.41, p = 0.003]. There was a negative association

between child hyperactivity (SDQ) and amplitude of the three

slow waves to anger at occipital areas (r = -0.50, p = 0.002). No

association emerged with conduct problems (r = -0.22,

p = 0.18). Associations did not hold after controlling for ampli-

tudes to neutral faces (r = -0.24, p = 0.17). This is the first ERP

study of emotion processing in school aged children with

hyperactivity.

Keywords: emotion processing, externalizing symptoms, children,

event-related potentials (ERP)


123

Emotional-motivational deficits in ADHD subtypes

A. Conzelmann1, R. F. Mucha1, C. P. Jacob1, P. Weyers1, A.Warnke1,A.J. Fallgatter1, K.-P. Lesch1, P. Pauli1

1University of Wurzburg, Wurzburg, Germany

Introduction and objectives: This study examined the affective

modulation of ADHD subtypes.

Methods: One-hundred ninety-seven medication-free adults with

ADHD (127 with ADHD combined type, ADHD-C; 50 with inat-

tentive type, ADHD-I; 20 with hyperactive-impulsive type, ADHD-

HI) and 128 controls took part. We obtained the startle reflex elicited

during pleasant, neutral and unpleasant IAPS pictures as well as the

valence and arousal ratings of the pictures.

Results: ADHD-C showed a lack of startle inhibition and ADHD-I a

slightly reduced inhibition during pleasant stimuli. ADHD-HI did not

show any affective startle modulation. Subjective data indicated

higher pleasure ratings of ADHD-HI and lower arousal of male

ADHD-HI concerning unpleasant pictures.

Discussion: ADHD-C shows an emotional deficit for pleasant and

ADHD-HI for pleasant and unpleasant stimuli. ADHD-I reacts rela-

tively normal.

Conclusion: Blunted emotional reactivity is especially pronounced in

ADHD patients with symptoms of hyperactivity and impulsivity.

Keywords: ADHD subtypes, Emotion, Startle reflex, Valence,

Arousal

Empathy in 6–7-year-old children with ADHD: a facial

electromyography approach

P.K.H. Deschamps1,3, L. Coppes1, L. Kenemans2, D.J.L.G. Schutter2,W. Matthys1,3

1Department of child- and adolescent psychiatry, University Medical

Centre Utrecht, Utrecht, The Netherlands; 2Department of

Experimental Psychology, Utrecht University, Utrecht, The

Netherlands; 3Rudolf Magnus Institute of Neuroscience, University

Medical Centre Utrecht, Utrecht, The Netherlands

Introduction: A precondition for empathy is to perceive and mimic

emotional expressions of others. Deficits in empathy have been

reported in patients with disruptive behavior disorder (DBD). Pre-

liminary studies suggest empathic deficits in attention deficit/

hyperactivity disorder (ADHD). However, facial mimicry studies in

young children with ADHD with and without comorbid DBD are

presently lacking.

Aim: Empathic mimicry in young 6–7-year-old ADHD children with

and without DBD was compared to healthy matched controls.

Methods: Facial electromyographic activity (EMG) to the presenta-

tion of a series of dynamic emotional faces (i.e., happy, sad, fear and

anger) was recorded in 49 participants aged 6–7 years.

Results: ADHD children with and without DBD (n = 17) demon-

strated lower facial EMG responses to sad faces as compared to

healthy children (n = 32) (p = 0.01). No group differences were

found for EMG responses to happy, fear and angry expressions (all

p [ 0.30).

Conclusion: The presently observed abnormal facial EMG responses

to sad faces may suggest reduced empathic capacities in ADHD

children with and without DBD that is already present at a relative

early age.

Keywords: Empathy, Facial EMG-mimicry, Children, ADHD, DBD

Structural brain changes in the emotional network

in adult patients with ADHD compared to patients

with major depression and healthy volunteers

Thomas Frodl1, Francesco Amico1, Julia Stauber2, Nadine Schaaff2,Nikolaos Koutsouleris2, Maximilian Reiser2, Hans-Jurgen Moller2

1Department of Psychiatry, School of Medicine, Trinity College

Institute of Neuroscience (TCIN), Trinity College, University of

Dublin, Trinity Centre for Health Sciences, Trinity Academic

Medical Centre (The Adelaide and Meath Hospital incorporating the

National Children’s Hospital (AMNCH) and St. James’s Hospital),

Dublin 24, Ireland; 2Ludwig-Maximilian University, Nussbaumstr. 7,

80336 Munich, Germany

Introduction and objectives: The neurobiological underpinnings of

comorbidity in adult ADHD are unclear. To investigate whether adult

ADHD patients may exhibit gray and/or white matter volumetric

abnormalities compared to healthy volunteers and patients with major

depression.

Methods: Twenty adult patients with ADHD, 20 patients with major

depression and 20 healthy controls (matched for age and gender) were

investigated using high-resolution magnetic resonance imaging.

Results: Smaller volumes were detected in the right and left anterior

cingulate cortex and in the amygdala in patients with ADHD com-

pared to patients with major depression and healthy controls.

Hyperactivity, Inattention and symptoms of depression were associ-

ated amygdala volumes.

Discussion: Adults with ADHD exhibit smaller ACC and amygdala

volumes. The present study supports findings that the emotional

neural network, which includes amygdala and the ACC, plays an

important role in the systemic brain pathophysiology of adult ADHD.

Conclusion: Whether symptoms of patients with ADHD, who show

structural brain changes in the emotional network, are more likely to

persist into adulthood compared to those with no or less structural

brain changes needs further investigation.

Reward sensitivity and choice behaviour of children

with ADHD

Stephanie Jensen1, Cara McAlpine1, Brent Alsop1

1University of Otago, Dunedin, New Zealand

Introduction: Treatment programs for ADHD typically include a

behavioural component which uses reward to increase desired

behaviour and punishment to decrease unwanted behaviour. Recent

research has identified that children with ADHD may respond dif-

ferently to reward than children without ADHD.

Objective: The present study uses a computer task to examine how

quickly children’s behaviour responds to changes in reward when the

contingencies are reversed.

Method: A signal-detection task was used to track changes in

response bias after reversals of the rich and lean choice alternatives.

Results: Data collection is ongoing. Preliminary results compare

performance from children with ADHD to a sample taken from the

general population. These data show that children’s behaviour chan-

ged rapidly in response to changing reinforcement contingencies.

Discussion: Based on previous research, it is expected that the chil-

dren with ADHD will be atypically sensitive to reinforcement,

and that their behaviour will exhibit a higher degree of control by


123

individual reinforcers (rather than by the overall pattern of reinforc-

ers) than the behaviour of children without ADHD will.

Keywords: ADHD, Children, Behaviour, Reward sensitivity

The psychological and physiological stress response

in ADHD

Robert Kumsta1, Edmund Sonuga-Barke1

1Developmental Brain-Behaviour Laboratory, School of Psychology,

University of Southampton, University of Southampton, UK

Introduction and objective: Recent research findings suggest an

important role of stress reactivity in ADHD. The aim of this paper is

to present an overview of research which investigated the behavioural

and physiological stress response in ADHD.

Methods: Experimental studies suggest that while ADHD patients

and healthy adults with high ADHD scores showed increased sub-

jective stress experience, they showed lower heart rate and cortisol

stress responses, indicative of a dissociation between subjective and

physiological responses [1] (Kumsta, in preparation).

Results: The central stress processing systems interact with other

CNS elements that influence the setting of emotional tone, the

retrievability and analysis of information, and also with dopaminergic

systems implicated in ADHD.

Discussion: Dysregulations of the HPA axis have been associated

with various psychiatric disorders. The evidence seems to suggest that

there is a dissociation between stress response systems in ADHD,

with increased subjective reactivity and insufficient physiological

activation.

Conclusion: Future research should be aimed at a thorough charac-

terization of unstimulated HPA axis activity in ADHD patients, as

well as multi-method investigations of stress reactivity in laboratory

and real-life settings.

Reference

1. Lackschewitz H, Huther G, Kroner-Herwig B (2008) Psycho-

neuroendocrinology 33(5):612–624

Social responsiveness in children and adolescents

with ADHD: an exploratory study

Laura Lecca1, Laura Anchisi1, Laura Delitala1, Giovanni Ambu1,Alessandro Zuddas1


Cagliari, Cagliari, Italy

Introduction and objective: A possible overlapping in neuropsy-

chological functioning has been described between ADHD and PDD.

This study evaluates frequency of social responsiveness difficulties in

subjects with ADHD.

Methods: Seventy-one drug-naıve or medication-free ADHD patients

(60 males, aged 5–16 years) were evaluated by SRS and CPRS and

scores of each subscale were compared with matched controls.

Results: 45% of ADHD subjects, versus none of controls, showed

SRS total T score higher than threshold score. In ADHD group total

SRS score correlated to all Conners subscales except Anxious/Shy

and Psychosomatic. In ADHD with comorbidity for internalizing or

learning disorders, anxiety and inattention correlated with social

motivation and hyperactivity with autistic mannerisms. In the other

patients, externalizing symptomatology correlated with autistic

mannerisms.

Discussion and conclusions: The study confirms that children and

adolescents with ADHD may show a clinically significant impairment

in social responsiveness, partially modulated by specific comorbidi-

ties: this should be considered a specific target for a comprehensive

therapeutic intervention.

References


(2004) How specific are executive functioning deficits in

attention deficit hyperactivity disorder and autism? J Child


2. Nijemeijer JS, Hoekstra PJ, Minderaa RB, Buitelaar JK, Altink

ME et al (2009) PDD symptoms in ADHD, an independent

familiar trial. J Abnorm Child Psychol 37:443–453

3. Reiersen AM, Constantino JN, Volk HE, Todd RD (2007)

Autistic traits in a population-based ADHD twin sample. J Child


Adolescent emotional and behavioural outcomes

of nonparental preschool childcare

Holan Liang1, Andrew Pickles2, Nicky Wood1, Emily Simonoff1

1King’s College London, Institute of Psychiatry, London, UK;2University of Manchester, Manchester, UK

Objective: This study aimed to identify whether nonparental pre-

school childcare was associated with adolescent mental health

outcomes as measured by the strengths and difficulties questionnaire

(SDQ).

Method: This study was a secondary analysis of data from the

Croydon assessment of learning study. From a general population

sample of 2,726 adolescents tested for cognitive ability, data were

collected from a stratified sub-sample of 197 participants. A semi-

structured interview asked parents about childcare and early devel-

opment concerns. Parent and teacher SDQ data were collected. Using

nonparental childcare as the ‘treatment’ effect and parental childcare

as the ‘control’, propensity score matching analyses were used to

analyse the effect of nonparental childcare on SDQ outcomes in

adolescence.

Results: Nonparental childcare was not significantly associated with

any SDQ outcomes save for symptoms of attention/hyperactivity, on

average raising the symptom subscale score by 1.8. The propensity

score analysis makes it unlikely that the results could be explained by

available measures of factors influencing receipt of nonparental care.

Conclusions: Nonparental preschool care showed little association

with generalized psychopathology but may be associated with

hyperactivity and inattention problems.

Dissociation of cognitive and emotional empathy

in autism and conduct disorders: the MET-J

Luise Poustka1, Anna Rehm1, Boris Rothermel1, Sabina Steiner1,Tobais Banaschewski1, Isabel Dziobek2


Central Institute of Mental Health, Mannheim, Germany; 2Cluster

Languages of Emotion, FU Berlin, Berlin, Germany


123

Background: Both autism spectrum disorders (ASD) and conduct

disorders (CD) have been described as disorders of empathy. In the

current study, we used a new, photo-based measure, the multifaceted

empathy test for adolescents (MET-J) to assess simultaneously cog-

nitive and emotional empathy in a group of adolescents with ASD and

CD aged 12–17 years.

Methods: 15 adolescents with ASD, 15 adolescents with CD and 15

typically developing controls closely matched for age, sex and IQ

were examined using the MET-J. Results were compared to results of

well-validated self-report questionnaires assessing empathy (IRI,

EQ).

Results: Groups differed significantly on both components of empa-

thy. Adolescents with ASD showed impairments in cognitive

empathy, but did not differ from healthy controls in emotional

empathy. Adolescent with CD showed an inverted pattern of disso-

ciation of empathy components, compared to adolescents with ASD.

Discussion: The double dissociation of cognitive and emotional

empathy observed in ASD and CD could provide a more precise

characterization of the behavioral phenotype of individuals affected

by empathy impairments.

Conclusions: A common classification of ASD and disorders with

disruptive behavior or psychopathic traits as empathy disorders

should be regarded with caution.

References

1. Dziobek I, Rogers K et al (2008) Dissociation of cognitive and

emotional empathy in adults with Asperger syndrome using the

multifaceted empathy test (MET). JADD 38:464–473

2. Blair RJ (2005) Responding to the emotions of others: sissoci-

ating form of empathy through the study of typical and

psychiatric populations. Conscious Cogn 14:698–718

Emotional lability in children and adolescents

with attention deficit/hyperactivity disorder (ADHD):

clinical correlates and familial prevalence

Esther Sobanski1, Tobias Banaschewski,2,12, Philip Asherson3,Jan Buitelaar5, Wai Chen3,4,17, Barbara Franke5,16,Martin Holtmann2, Bertram Krumm15, Joseph Sergeant6,Edmund Sonuga-Barke3,4,11,18, Argyris Stringaris3, Eric Taylor3,Richard Anney8, Richard P. Ebstein7, Michael Gill8, Ana Miranda9,Fernando Mulas9, Robert D. Oades10, Herbert Roeyers11,Aribert Rothenberger12, Hans-Christoph Steinhausen13,19,Stephen V. Faraone14

1Department of Psychiatry and Psychotherapy, Central Institute of

Mental Health, Mannheim, Germany; 2Departmentof Child and

Adolescent Psychiatry, Central Institute of Mental Health, Mannheim,

Germany; 3MRC Social Genetic Developmental and Psychiatry

Centre, Institute of Psychiatry, London, UK; 4School of Psychology,

University of Southampton, Southampton, UK; 5Department of

Psychiatry, Donders Institute for Brain, Cognition and Behavior,

Centre for Neuroscience, Radboud University Nijmegen Medical

Center, Nijmegen, The Netherlands; 6Clinical Neuropsychology,

Vrije Universiteit, Amsterdam, The Netherlands; 7S. Herzog

Memorial Hospital, Jerusalem, Israel; 8Trinity Centre for Health

Sciences, St James’s Hospital, Dublin, Ireland; 9Department of

Developmental and Educational Psychology, University of Valencia,

Valencia, Spain; 10University Clinic for Child and Adolescent

Psychiatry and Psychotherapy, Essen, Germany; 11Departments of

Experimental Clinical Health Psychology, Ghent University, Ghent,

Belgium; 12Child and Adolescent Psychiatry, University of

Goettingen, Gottingen, Germany; 13Department of Child and

Adolescent Psychiatry, University of Zurich, Zurich, Switzerland;14Departments of Psychiatry and Neuroscience and Physiology,

SUNY Upstate Medical University, Syracuse, NY, USA;15Department of Biostatistics, Central Institute of Mental Health,

Mannheim, Germany; 16Department of Human Genetics, Radboud

University Nijmegen Medical Center, Nijmegen, The Netherlands;17Clinical Neurosciences Division, School of Medicine, University of

Southampton, Southampton, UK; 18Child Study Center, New York

University, New York, USA; 19Child and Adolescent Psychiatry,

Aarhus University Hospital, Aalborg, Denmark

Background: We investigated clinical correlates of emotional lability

(EL) in children with attention deficit/hyperactivity disorder (ADHD),

and examined factors contributing to EL in ADHD.

Methods: 1,186 children with ADHD combined type and 1,827 sib-

lings were assessed for symptoms of EL, ADHD, associated

psychopathology and comorbid psychiatric disorders with a structured

diagnostic interview as well as parent and teacher ratings of

psychopathology.

Results: Mean age and gender-standardized ratings of EL in children

with ADHD were [1.5 SD above the mean in normative samples.

Severe EL ([75th percentile) was associated with more severe ADHD

core symptoms and more comorbid oppositional defiant, affective and

substance use disorders. Age, hyperactive-impulsive, oppositional,

and emotional symptoms accounted for 30% of EL variance; with

highest impact of oppositional symptoms. Severity of EL in probands

increased the severity of EL in siblings, but not the prevalence rates of

ADHD. EL and ADHD does not co-segregate within families.

Conclusion: EL is a frequent clinical problem in children with

ADHD. It is associated with increased severity of ADHD core

symptoms and more symptoms of comorbid psychopathology. EL in

ADHD seems to be more closely related to ODD than to ADHD core

symptoms, and is only partly explainable by the severity of ADHD

core symptoms and associated psychopathology. EL in children with

ADHD does not increase the risk of ADHD in their siblings.

Emotion regulation and performance on a flanker task

in adults with ADHD

V. Van Cauwenberge1, J.R. Wiersema1, I. Buyck1

1Ghent University, Ghent, Belgium

Introduction and objective: Studies have demonstrated lower

effortful control (EC) in children with ADHD [2]. One important

feature of EC is the resistance to interference [1]. The current study

examined the link between interference control, EC, and emotion

regulation in healthy adults and adults with ADHD.

Method: Resistance to interference was measured by a flanker task.

Scores for EC and emotion regulation were obtained through

questionnaires.

Results: After preliminary analyses we found that adults with ADHD

were slower and more variable in their responding than controls. Both

groups showed equally large congruency effects for response speed

and accuracy and did not differ in number of errors. Adults with

ADHD showed lower scores for EC and emotion regulation than

controls. The strongest correlation appeared between the interference-

effect for errors and emotion regulation, which was significant for

both groups.

Discussion: The results suggest intact interference control in adults

with ADHD. Surprisingly, emotion regulation was stronger related to

interference control than EC.

Conclusion: The role of emotion regulation in ADHD needs further

specification.


123

References

1. Rothbart MK, Ellis LK, Rueda MR, Posner MI (2003) Devel-

oping mechanisms of temperamental effortful control. J Pers

71(6):1113–1144

2. Wiersema JR, Roeyers H (2009) ERP correlates of effortful

control in children with varying levels of ADHD symptoms. J

Abnorm Child Psychol 37:327–336

Sleep and emotional reactivity to extended release

dexmethylphenidate versus mixed amphetamine salts:

a double-blind, placebo controlled study

Sabrina Wiebe1, Reut Gruber1,2, Elizabeth Charney3, Subhash Aryal4,Irwin Waldman5, Jeffrey Newcorn6, Mark Stein3

1Douglas Mental Health University Institute, Montreal, Canada;2McGill University, Montreal, Canada; 3Institute for Juvenile

Research, University of Illinois, Chicago, USA; 4UNT Health Science

Center, Fort Worth, TX, USA; 5Emory University, Atlanta, GA, USA;6Mount Sinai School of Medicine, New York, NY, USA

Introduction and objective: Attention-deficit/hyperactivity disorder

(ADHD) is a common childhood disorder. Children with ADHD often

display sleep problems and mood instability, which are exacerbated

with stimulant medication. This study examined the relationship

between sleep and emotional reactivity to dexmethlyphenidate

(DMPH) and mixed amphetamine salts (MAS).

Methods: Forty children, aged 9–17, participated in a double-blind

crossover study comparing two stimulants (extended release DMPH,

MAS) at three doses (10, 20, 25–30 mg), with two randomized pla-

cebo periods. Treatments lasted 1 week. Sleep and emotional

reactivity were assessed using actigraphy and questionnaires.

Results: Higher dosages reduced sleep duration, regardless of medi-

cation. Sleep was differentially related to emotional reactivity across

medications, with later wake time being correlated with decreased

depression, anger and anxiety scores during DMPH treatment, while

no consistent relationship was found for MAS.

Discussion: Although sleep deteriorated with dosage, later wake

times were associated with less negative emotionality for DMPH,

suggesting improved sleep may prove particularly beneficial with this

stimulant.

Conclusion: The relationship between sleep and emotionality sug-

gests a need for combined sleep and stimulant treatment to increase

tolerability and treatment compliance.

Poster Sessions H: Miscellaneous andLate Submissions

Increased response time variability across different

cognitive tasks in medication-free children with ADHD

Nicoletta Adamo1, Adriana Di Martino1,2, Lidia Esu1,Katherine Johnson3, F. Xavier Castellanos2,4, Alessandro Zuddas1


Cagliari, Cagliari, Italy; 2Institute for Pediatric Neuroscience, NYU

Child Study Center, New York, NY, USA; 3School of Psychology,

Queen’s University Belfast, Belfast, Northern Ireland; 4Nathan Kline

Institute for Psychiatric Research, Orangeburg, NY, USA

Introduction/objective: Increased response time intra-subject vari-

ability (RT-ISV) in ADHD [1, 2], measured as slow fluctuations, was

not replicated [3], possibly due to differences in tasks. We examined

RT-ISV on two different tasks in children with DSM-IV ADHD

compared to typically developing children (TDC).

Methods: All participants (50 ADHD and 49 TDC) completed an

Eriksen Flanker Task (EF) and a fixed-sequence version of the sus-

tained attention to response task (SART) in a single session. To

minimize medication effects we included only children who were

medication naıve or off stimulants for at least 1 week prior to testing.

Results: Significantly higher RT-SD was measured in ADHD for both

tasks: EF = 125.2 ± 27.3 versus 90.6 ± 22.3, in ADHD and TDC,

respectively and SART = 202.2 ± 58.8 versus 138.6 ± 39.9, in

ADHD and TDC, respectively. RT-SD was significantly correlated in

both groups across tasks (r = 0.61, p \ 0.01, and r = 0.78, p \ 0.01,

in ADHD and TDC, respectively).

Conclusions: These findings confirm that different tasks can detect

significantly increased ISV in a medication-free group of children

with ADHD.

References

1. Di Martino A, Ghaffari M, Curchack J, Reiss P, Hyde C,

Vannucci M, Petkova E, Klein DF, Castellanos FX (2008)

Decomposing intra-subject variability in children with attention-

deficit/hyperactivity disorder. Biol Psychiatry 64:607–614

2. Johnson KA, Kelly SP, Bellgrove MA, Barry E, Cox M, Gill M,

Robertson IH (2007) Response variability in attention deficit

hyperactivity disorder: evidence for neuropsychological hetero-

geneity. Neuropsychologia 45:630–638

3. Geurts HM, Grasman RP, Verte S, Oosterlaan J, Roeyers H, van

Kammen SM, Sergeant JA (2008) Intra-individual variability in

ADHD, autism spectrum disorders and Tourette’s syndrome.


Emotional lability, SLC6A4/5-HTT and DRD4

genotypes in attention deficit hyperactivity disorder

(ADHD): genetic substrates for emotional

dysregulation, or distinctive ADHD subtypes?

Wai Chen1,2,3, Tobias Banaschewski4, Barbara Franke5,Eric A. Taylor3, Edmund J.S. Sonuga-Barke2,3,6,7, Wolff Schlotz2,Katya Rubia3, Robert D. Oades8, Margaret J. Thompson2,Jan Buitelaar9, Henrik Uebel10, Aisling Mulligan11,Richard J.L. Anney11, Darko Turic2, David Daley12,Martin Holtmann4, R.P. Ebstein13, Michael Gill11, Ana Miranda14,Fernando Mulas15, Herbert Roeyers6, Aribert Rothenberger10,Joseph A. Sergeant16, Hans-Christoph Steinhausen17,18,19,Stephen V. Faraone20, Philip Asherson3

1Clinical Neurosciences Division, School of Medicine, University of

Southampton, Southampton, UK; 2School of Psychology, University

of Southampton, Highfield, Southampton, UK; 3MRC Social Genetic

Developmental and Psychiatry Centre, Institute of Psychiatry,

London, UK; 4Department of Child and Adolescent Psychiatry,

Central Institute of Mental Health, Mannheim, Germany;5Departments of Human Genetics and Psychiatry, Donders Institute

for Brain, Cognition and Behavior, Radboud University Nijmegen

Medical Centre, Nijmegen, The Netherlands; 6Departments of

Experimental Clinical Health Psychology, Ghent University, Ghent,

Belgium7Child Study Center, New York University, New York, USA;8University Clinic for Child and Adolescent Psychiatry and

Psychotherapy, Essen, Germany; 9Department of Cognitive

Neurosciences, Donders Institute for Brain, Cognition and Behavior,


123

Radboud University Nijmegen Medical Centre, Nijmegen, The

Netherlands; 10Child and Adolescent Psychiatry, University of

Gottingen, Gottingen, Germany; 11Trinity Centre for Health Sciences,

St James’s Hospital, Dublin, Ireland; 12North Wales Clinical

Psychology Programme, School of Psychology, College of Health and

Behavioural Science, Bangor University, North Wales, UK; 13S.

Herzog Memorial Hospital, Jerusalem, Israel; 14Department of

Developmental and Educational Psychology, University of Valencia,

Valencia, Spain; 15Neuropediatric Service University Hospital La Fe,

Valencia, Spain; 16Clinical Neuropsychology, Vrije Universiteit,

Amsterdam, The Netherlands; 17Department of Child and Adolescent

Psychiatry, University of Zurich, Zurich, Switzerland; 18Aalborg

Psychiatric Hospital, Aarhus University Hospital, Aalborg, Denmark;19Institute of Psychology, University of Basel, Basel, Switzerland;20Departments of Psychiatry and Neuroscience and Physiology,

SUNY Upstate Medical University, Syracuse, NY, USA

Background: Emotional lability (EL) is a common feature of atten-

tion deficit hyperactivity disorder (ADHD), but not all patients are

affected. We examined the associations between EL and genotypes of

the SLC6A4/5-HTT and DRD4 genes.

Method: 1,744 children from the IMAGE project were examined for

associations between EL and genotypes of the 5-HTTLPR (long

versus short allele) and the VNTR in exon 3 of DRD4.

Results: Significant associations were detected between EL and (1)

the 5-HTTLPR S/S genotype (OR 1.53; p = 0.003) as well as (2) the

DRD4 7R-homozygous genotype (OR 1.77; p = 0.027). When the

sample was stratified into ADHD-affected and unaffected individuals,

significant associations were only detected in the ADHD-affected

group. Genotypic patterns in ‘ADHD + EL-only’, ‘ADHD + ODD-

only’ and ‘ADHD + EL + ODD’ versus ‘ADHD-only’ cases were

compared. The 5-HTTLPR SS genotype predicted ‘ADHD + E-

L + ODD’ cases (OR 2.05; p = 0.011), the DRD4 7R-homozygous

genotype predicted ‘ADHD + EL-only’ cases (OR 32.77; p = 0.002)

and no genotype predicted ‘ADHD + ODD-only’ cases.

Discussion: Our findings provide evidence that EL in ADHD has a dis-

tinctive genetic profile. Our findings may signify specific genetic risks for

EL amongst ADHD subjects or genetically distinct subtypes of ADHD.

Junior Conference Lectures

ADHD as predictive factor of poor outcome in pediatric

bipolar disorder

Sara Carucci1, Paola Atzori1, Carla Balia1, Fabrice Danjou2,Alessandro Zuddas1


Cagliari, Cagliari, Italy; 2Biomedical Science and Biotechnologies,


Introduction: Recognition that bipolar disorder (BD) can occur

during adolescence and probably during childhood is currently well

established, but its phenomenology and clinical prevalence during

development continue to be controversial [1]. BD meeting full DSM-

IV criteria is very rare in pre-pubertal children and debate on clas-

sification of severe non-episodic irritability as BD-NOS or Severe

Mood Dysregulation continue to be a challenging and controversial

argument [2]. Several investigations are under way in order to define

whether the strong association with externalizing disorders such as

comorbidity with ADHD, the family history as well as the longitu-

dinal course of the disorder may be appropriate criteria to define a

specific phenotype. A better understanding of the clinical presentation

and longitudinal outcome of pediatric bipolar disorder is essential for

improving early diagnosis and for advancing appropriate treatment

strategies and neurobiological research.

Objectives: The aim of the study was to describe the demographic

and clinical characteristics of children and adolescents with bipolar

disorder I (BP-I), II (BP-II) and not otherwise specified (BP-NOS)

and to explore the possible influence of ADHD comorbidity on drug

response and clinical outcome 24 months after the initial hospital-

ization within the three groups.

Methods: The medical charts of 71 inpatients, aged 6–18 years,

meeting DSM-IV diagnostic criteria for BP-I (n = 45), BP-II (n = 10)

and BP-NOS (n = 16) were retrospectively reviewed. Data regarding

clinical presentation, previous psychiatric and medical illnesses, psy-

chiatric comorbidity and parental psychopathology were obtained

during the admission. The diagnosis was established based on the

results of the semi-structured interview K-SADS-PL and on the clinical

assessment by a child and adolescent neuropsychiatrist. The patients

were followed up for 24 months and the longitudinal course of the

disorder was assessed at baseline, 6, 12 and 24 months by the children

global assessment scale (C-GAS).

Data analysis: Categorical comparisons were based on contingency

tables (v2); continuous variables were compared by one-way

ANOVA. Repeated measures ANOVA was performed for C-GAS

scores at baseline, 6-, 12- and 24-month follow-up. Statistical sig-

nificance required two-tailed p B 0.05.

Results: BP-NOS significantly differed from BP-I in age of onset

(11.2 ± 3.3 years vs. 15.2 ± 2; p \ 0.001), in lifetime rates of comorbid

diagnosis (BP-NOS had higher rates of ADHD and ODD; p = 0.001

and = 0.05, respectively) and from both BP-I and II in the types of mood

symptoms that lead to the admission (BP-I had more severe manic

symptoms and higher rates of psychosis, p \ 0.005; BP-II had more

severe depressive symptoms, p \ 0.05). There were no significant dif-

ferences among the three groups in IQ, family history and polarity of the

first affective episode (mainly presenting with mixed episodes). Most of

BP-II and BP-NOS have been chronically treated with mood stabilizers

while more than the 50% of BP-I needed to be treated with a combined

treatment of mood stabilizers and antipsychotics (p = 0.04). Despite a

similar severity of illness between BP-NOS and BP-II at baseline, and a

relatively comparable pharmacologic approach within the three groups,

the longitudinal outcome, assessed by C-GAS, showed a poorer func-

tional outcome for BP-NOS after 24 months (p = 0.010), confirming

diagnosis to be a predictor for the longitudinal outcome. Between sub-

jects effects calculated with repeated measures ANOVA revealed IQ and

sex to affect CGAS in the way that patients with lower IQ (p = 0.006)

and female sex (p = 0.026) were more impaired. Finally, ADHD

appeared as a predictor of a poorer outcome within the sample of all

bipolar patients presenting with normal IQ (p = 0.003).

Conclusion: These findings validate the existence of different sub-

types of pediatric bipolar disorder and confirm that BD-NOS present

with a more complex clinical and biological heterogeneity compared

to BD-I and BD-II. Subjects with an earlier onset and ADHD

comorbidity tended in fact to present a worse outcome with a poorer

response to treatments and higher functional impairment after 2 years.

A better definition of the disorder and a better understanding of its

features in the different populations appear to have significant treat-

ment implications. Innovative therapeutic approaches are urgently

required to address the clinical needs of these severe impaired patients

and improve their clinical outcome and global functioning.

References

1. Leibenluft E, Rich BA (2008) Pediatric bipolar disorder. Annu

Rev Clin Psychol 4:163–187

2. Stringaris A, Santosh P, Leibenluft E, Goodman R (2010) Youth

meeting symptom and impairment criteria for mania-like epi-

sodes lasting less than 4 days: an epidemiological enquiry. J

Child Psychol Psychiatry 51:31–38


123

Interactions of self-concept, social support

and expressed emotion in families with ADHD

Hanna Christiansen1, Ann-Kathrin Bangert1, Bernd Rohrle1,Robert D. Oades2



Child and Adolescent Psychiatry and Psychotherapy, Essen, Germany

Introduction and objective: Self-concept (SC) serves as a reference

frame and source of self-knowledge. ADHD children are known to

have significantly reduced self-esteem possibly due to parental

expressed emotion (EE), i.e. criticism/hostility. We present the first

study on the influence of social support (SOS) on EE in ADHD

families and SC of the child.

Methods: A total of 62 ADHD children and their parents and 61

matched control families filled out questionnaires on SOS/SC and

ADHD symptoms; parental EE was assessed. Regressions to predict

child SC with SOS, EE, and symptom severity were calculated. The

Sobel-test was used to test for mediation effects.

Results: SC was significantly reduced in children with ADHD.

ADHD parents received significantly less SOS and showed more EE.

ADHD symptom severity predicted negative child SC as did SOS and

EE. Parental EE significantly mediated the path between parental SOS

and child SC.

Discussion: Parental SOS and EE both contribute to SC in the child as

does symptom severity.

Conclusion: Multimodal therapy should support parents, enhance

positive parenting and include treatment of low SC.

Keywords: Attention-deficit/hyperactivity disorder (ADHD), Social

support, Self-concept, Parents, Peers

Emotional-motivational deficits in ADHD subtypes

A. Conzelmann1, R.F. Mucha1, C.P. Jacob1, P. Weyers1, A. Warnke1,A.J. Fallgatter1, K.-P. Lesch1, P. Pauli1

1University of Wurzburg, Wurzburg, Germany

Introduction and objective: This study examined the affective

modulation of ADHD subtypes.

Methods: 197 medication-free adults with ADHD (127 with ADHD

combined type ADHD-C; 50 with inattentive type, ADHD-I; 20 with

hyperactive-impulsive type, ADHD-HI) and 128 controls took part.

We obtained the startle reflex elicited during pleasant, neutral and

unpleasant IAPS pictures as well as the valence and arousal ratings of

the pictures.

Results: ADHD-C showed a lack of startle inhibition and ADHD-I a

slightly reduced inhibition during pleasant stimuli. ADHD-HI did not

show any affective startle modulation. Subjective data indicated

higher pleasure ratings of ADHD-HI and lower arousal of male

ADHD-HI concerning unpleasant pictures.

Discussion: ADHD-C shows an emotional deficit for pleasant and

ADHD-HI for pleasant and unpleasant stimuli. ADHD-I reacts rela-

tively normal.

Conclusion: Blunted emotional reactivity is especially pronounced in

ADHD patients with symptoms of hyperactivity and impulsivity.

Keywords: ADHD subtypes, Emotion, Startle reflex, Valence,

Arousal

Fronto-striatal structural connectivity in ADHD

assessed using combined diffusion tensor

and magnetisation transfer imaging

Patrick de Zeeuw1, Rene C.W. Mandl2, Sarah Durston1



Utrecht, The Netherlands; 2Department of Psychiatry, Rudolf Magnus


Utrecht, The Netherlands

Introduction and objective: Fronto-striatal networks and the cog-

nitive functions supported by them have been suggested to be central

to ADHD. Indeed, these brain areas have been shown to have reduced

volume and brain activity in this disorder [1]. Recently, attention has

shifted from implicating distinct brain areas in ADHD towards con-

sidering brain networks. As such, a detailed assessment of the

structural connectivity between the striatum and the prefrontal cortex

is a timely step in characterising brain changes in ADHD.

The present study investigates the integrity of structural (white mat-

ter) connections between the striatum and the prefrontal cortex in

children with ADHD and controls. Two modalities of magnetic res-

onance imaging are used, addressing both the microstructural

organisation or directionality of white matter and the degree of

myelination [3]. Fractional anisotropy (FA), a measure derived from

diffusion tensor imaging (DTI), is used as an index of or directionality

of the white matter. Magnetisation transfer ratio (MTR), derived from

magnetisation transfer imaging (MTI), is used as an index of myeli-

nation of white matter fibres. General intelligence (IQ) was assessed

in order to relate the white matter measures to level of global cog-

nitive functioning of participants.

Methods: On a 1.5-T Philips MRI scanner, T1-weighted (SPGR),

DTI and MTI scans were acquired in 30 children with ADHD [three

girls, age range 6–14, M (SD) 9.6(2.3)] and 34 control children [four

girls, age range 6–15 M (SD) 10.2(2.3)]. T1-weighted scans went

through a standardised processing pipeline to obtain a segment of

total white matter (excluding the cerebellum). DTI and MTI scans

went through pre-processing as described previously [2]. A deter-

ministic tractography algorithm (FACT) was applied to resulting FA

maps in order to reconstruct all white matter fibres within the brain.

The fibres of each individual subject were then warped to a template

brain. White matter fibres connecting the striatum and prefrontal

cortex were selected for each individual subject using a region-of-

interest approach. Next, a group map of Fronto-striatal tracts was

made in order to form a groupwise Fronto-striatal volume of interest

(VOI). This VOI was then warped back to the individual native space

of each individual subject. Mean FA and MTR were measured in this

VOI as well as in the total cortical white matter (excluding the Fronto-

striatal VOI). IQ was assessed using a 4-subtest short form of the

WISC-IIINL.

Results: Fronto-striatal FA was decreased for children with ADHD

compared to controls (p \ 0.05). There was no difference in Fronto-

striatal MTR between groups. No group differences were observed in

total white matter FA or MTR. There were no correlations with age or

age by group interactions. For controls but not children with ADHD,

IQ was correlated with both FA [rADHD = 0.18 (p = 0.338),

rControl = 0.36 (p = 0.037)] and MTR [rADHD = 0.03 (p = 0.868),

rControl = 0.40 (p = 0.020)] in total white matter.

Discussion: Our results suggest that the directionality of Fronto-

striatal white matter tracts is affected in ADHD, but that this effect is

not caused by changes in myelination. Global cognitive functioning is


123

correlated with overall directionality (FA) and myelination (MTR) of

total white matter in control children. This suggests that better cog-

nitive functioning is associated with more efficient structural

connectivity in typical development. However, this correlation is not

found in children with ADHD, suggesting that cognitive functioning

in ADHD does not reflect connectivity in the same way, but rather

may represent other aspects of neurobiology.

Conclusion: Structural connectivity between prefrontal cortex and

striatum is affected in ADHD, supporting previous reports of fronto-

striatal involvement in this disorder. Furthermore, the directionality of

the white matter fibres appears to be more affected than myelination.

Furthermore, better global cognitive functioning is associated with

white matter connectivity for typically developing children, but not

for children with ADHD, suggesting that white matter may be more

widely affected in this disorder.

References

1. Durston S, de Zeeuw P, Staal WG (2009) Imaging genetics in

ADHD: a focus on cognitive control. Neurosci Biobehav Rev

33:674–689

2. Mandl RC, Schnack HG, Luigjes J, van den Heuvel MP, Cahn W,

Kahn RS, Hulshoff Pol HE (2008) Tract-based analysis of

magnetization transfer ratio and diffusion tensor imaging of the

frontal and frontotemporal connections in schizophrenia. Schiz-

ophr Bull. doi:10.1093/schbul/sbn161

3. Wozniak JR, Lim KO (2006) Advances in white matter imaging:

a review of in vivo magnetic resonance methodologies and their

applicability to the study of development and aging. Neurosci

Biobehav Rev 30:762–774

Temporal reward discounting in ADHD and ASD

Ellen Demurie1, Herbert Roeyers1, Edmund Sonuga-Barke1,2,Dieter Baeyens3

1Ghent University, Ghent, Belgium; 2University of Southampton,

Southampton, UK; 3Lessius University College, Antwerp, Belgium

Introduction and objective: As children with ADHD experience an

aversion to delayed reinforcement [3] and prefer small immediate

rewards over larger delayed rewards, a steeper discounting of delayed

rewards is hypothesized and often found in this clinical group [1].

Temporal discounting (TD) refers to the decrease of subjective

reward value as a function of increasing delay before reward delivery.

A steeper TD curve, thus faster subjective devaluation of a reward

with increasing delay, is associated with impulsivity and hyperac-

tivity. The few TD studies in children and adolescents with ADHD

have only used monetary rewards [1, 2]. Recent studies with non-

clinical samples show that directly consumable, primary reinforcers

show steeper TD than conditioned reinforcers such as money. In the

current study, we wanted to investigate to what extent TD in ADHD

differs for different types of rewards (monetary and non-monetary

rewards). Furthermore, we wanted to examine to what extent dis-

counting functions are disorder specific. To this extent, computerized

TD tasks were administered from children with ADHD, children with

ASD and typically developing children.

Methods: 46 typically developing control children and adolescents,

39 children and adolescents with ADHD and 34 children and ado-

lescents with ASD participated in this study. All children (8–

11 years) and adolescents (12–16 years) had an estimated full scale

IQ of 80 or more. Participants played two computerized tasks. In a

first task, children rated 30 pictures of one of the four alternative

reinforcers on a 7-point scale, ranging from 1 (not nice at all to

receive this reward) through 4 (neutral) to 7 (really nice). Participants

were assigned to one of four alternative reward conditions (activities,

material rewards, food and social reinforcement) randomly. Based on

the above rating process, a ranking of different types of rewards was

made and the subjective value of each reward in percentages was

calculated, with 0% as neutral and 100% as most reinforcing. In the

second task, the actual TD task, participants were instructed to make

repeated choices between a (hypothetical) small variable reward

delivered immediately (now) and a large constant reward delivered

after a variable delay (now, tomorrow, the day after tomorrow,

1 week, 2 weeks). This task consisted of two parts: a monetary TD

task and an alternative reward TD task. Rewards in the monetary TD

task were 0, 5, 10, 20 and 30 €, visualized as euro notes. Rewards in

the alternative reward TD task were the rewards from the first task

with assigned subjective values (as close as possible to) 0, 16.67,

33.33, 66.67 and 100%. Dependent variable in this task was the area

under the curve (AUC) for the TD functions. The steeper the dis-

counting function, the smaller the total AUC will be.

Results: In the monetary TD task the AUC of the ADHD group was

significantly lower than the AUC of the controls and the ASD group.

No effect of age group was found. Extra analyses showed that the

normalized subjective value of the large reward (SV-LR) became

smaller with increasing delay. Furthermore, a trend for an interaction

effect between delay and group was found for this function. The effect

of delay before rewards was different in the participating groups.

In the alternative reward TD tasks a significant main effect of age

group and a trend for a main effect of alternative TD condition were

found. AUC of children was higher than AUC of adolescents. AUC

for material rewards was significantly higher than the AUC for edible

rewards. The remaining AUC’s were not significantly different. A

group effect was found only in the social reward TD task. There was a

higher AUC in the control group compared to the group with ADHD.

Extra analyses showed that the normalized SV-LR became smaller

with increasing delay in the activities, material and eatable rewards

TD tasks.

If the monetary and alternative reward TD tasks were compared, a

significant main effect of TD task was found for the activities and

edible reward TD tasks. The AUC in the monetary TD task was

significantly higher than the AUC in the two alternative TD tasks.

Furthermore significant main effects of group and alternative TD

condition were found. The AUC of the ADHD group was lower than

the AUC of the control group and the ASD group in the monetary and

social reward TD task. The AUC of participants who did the material

reward TD task was higher than the AUC of participants who did the

eatable reward TD task.

Discussion and conclusion: Contrary to Scheres et al. [2], we did find

a difference in TD of monetary rewards between children and ado-

lescents with ADHD on the one hand and typically developing

children and adolescents, and children and adolescents with ASD on

the other hand. We found this group difference even in a hypothetical

TD task, which is supposed to be less sensitive than TD tasks with

real rewards. This suggests that children and adolescents with ADHD

may have insight into their delay aversion and associated behaviours.

A factor that may have contributed to the fact that we did find a group

difference in the monetary TD task is that we used more realistic

amounts of money than used previously. Scheres et al. [2] concluded

that it is possible that strong preferences for small immediate rewards

in ADHD depend on factors such as total maximum gain. Also

Barkley et al. [1] found that magnitude of the hypothetical delayed

rewards during a TD task differentially affected reward preferences in

adolescents with ADHD. In contrast to Scheres et al. [2] who used

very small amounts of money and Barkley et al. [1] who used high to

very high amounts of money, we used amounts of money that can be

given as pocket money to children.

In the alternative reward TD tasks, a group difference was only

found in the social TD task. The fact that we did not find any group

effects in the other alternative reward conditions might be due to


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http://dx.doi.org/10.1093/schbul/sbn161

limited power in the subgroups, but may also suggest that steeper TD

is not only dependent on magnitude of the hypothetical delayed

rewards, but also on the specific nature of the rewards. Moreover,

compared to activities and eatable rewards, money had a higher AUC

and thus a less steep TD slope. These non-monetary rewards are

transient and cannot be collected. Our results confirm previous studies

that show that directly consumable reinforcers show steeper TD than

conditioned reinforcers such as money.

References

1. Barkley RA, Edwards G, Laneri M, Fletcher K, Metevia L (2001)

Executive functioning, temporal discounting, and sense of time in

adolescents with attention deficit hyperactivity disorder (ADHD)

and oppositional defiant disorder (ODD). J Abnorm Child

Psychol 29:541–556

2. Scheres A, Dijkstra M, Ainslie E, Balkan J, Reynolds B, Sonuga-

Barke E, Castellanos FX (2006) Temporal and probabilistic

discounting of rewards in children and adolescents: Effects of age

and ADHD symptoms. Neuropsychologia 44:2092–2103

3. Sonuga-Barke EJS (2002) Psychological heterogeneity in AD/

HD—a dual pathway model of behaviour and cognition. Behav

Brain Res 130:29–36

Anxiety as a modulator of cognitive function depending

on ADHD subtype

M. Ferrin1,2,*, J.M. Granados-Moreno1, M.D. Salcedo-Marın1,M. Ruiz-Veguilla1, A.B. Ramırez-Gonzalez1, M.S. Centeno-Collado1,M.L. Barrigon-Estevez1,2, J.L. Rubio1,2

Neuro-Developmental Psychiatry Research Unit (NPD), Jaen, Spain;2Institute of Psychiatry, London, UK

Introduction: Few studies have compared cognitive functioning in

ADHD children and adolescents with or without comorbid anxiety.

Children with ADHD and anxiety have shown more impairment on

some tasks (e.g. Trail Making test B, working memory), but less on

others [2, 3]. Such contradictory findings may be explained by the

different effects of anxiety on the processing and storage of infor-

mation and motivation. The attention control theory (ACT) is an

approach to anxiety and cognition that further develops the previous

processing efficiency theory (PET). The ACT holds that anxiety

impairs executive function efficiency by disrupting the balance

between the stimulus-driven attentional system and the goal-directed

attentional system [1].

Objective: To explore the effects of anxiety in cognitive function

according to specific ADHD subtypes (combined or inattentive), and

in relation with previous theories regarding anxiety and cognitive

performance.

Methods: We included 78 patients with a diagnosis of ADHD

attending a Child and Adolescent Psychiatric service in Jaen (Spain).

Patients were divided according to the specific subtype (combined:

n = 55, and inattentive: n = 23). Independent variables were cog-

nitive function measured by (1) Rey Auditory Verbal Learning Test

for immediate, short- and long-term auditory memories, (2) short-

term visual memory and visual planning-organization ability mea-

sured by Rey-Osterreich Complex Figure, and (3) divided attention

measured by Trail Making Test B. Anxiety levels were assessed using

the Conners subscale for parental anxiety.

Results: Mean age was 11.26 ± 2.43 years for inattention subtype,

and 10.47 ± 3.27 years for the combined subtype. We found no

differences between subtypes for any of the variables explored.

Patients with low levels of anxiety (below median) showed similar

cognitive functioning in both the combined and the inattentive sub-

types. However, children with high levels of anxiety (above median)

showed a different pattern of functioning according to the specific

ADHD subtype. While improvement in the long-term auditory

memory was seen for the inattentive subtype, the combined type

showed worsening of long-term auditory memory, the differences

between groups being statistically significant (p \ 0.05). Similarly,

we obtained a positive interaction (p = 0.018) between the two

groups in the multivariable analysis, the inattentive subtype with high

levels of anxiety showing improvement in functioning, whereas

subjects with combined subtype and high levels of anxiety worsened

in function (p = 0.037). Again, a positive interaction (p = 0.026)

was found for divided attention, the combined type showing more

errors than the inattentive subtype (p = 0.010) when high levels of

anxiety were reported.

Discussion and conclusion: High levels of anxiety were seen to

affect long-term auditory memory and visual planning-organising

ability differently, depending on ADHD subtype. These results are in

line with previous theories about anxiety and cognitive performance

that suggest anxiety has a dual effect (worsening the processing and

storage capacity of working memory, while increasing motivation and

auxiliary processing resources), and enhances the influence of stim-

ulus-driven attention as opposed to goal-directed attention. Our

findings, while contradictory, coincide with the observations of some

previous studies.

*Corresponding author: [email protected]

References

1. Eysenck M W, Derakshan N, Santos R, Calvo MG (2007)

Anxiety and cognitive performance: attentional control theory.

Emotion 7(2):336–353

2. Pliszka SR (1989) Effect of anxiety on cognition, behavior, and

stimulant response in ADHD. J Am Acad Child Adolesc


3. Tannock R, Ickowicz A, Schachar R (1995) Differential effects

of methylphenidate on working memory in ADHD children with

and without comorbid anxiety. J Am Acad Child Adolesc


Emotional dysregulation and the serotonin transporter

gene in adult ADHD

E.T. Landaas1,2, S. Johansson1,2, A. Halmøy1, O.B. Fasmer3,4,J. Haavik1,4

1Department of Biomedicine, University of Bergen, Bergen, Norway;2Center of Medical Genetics and Molecular Medicine, Haukeland

University Hospital, Bergen, Norway; 3Department of Clinical

Medicine, Section for Psychiatry, Faculty of Medicine, University of

Bergen, Bergen, Norway; 4Division of Psychiatry, Haukeland

University Hospital, Bergen, Norway

Introduction and objectives: attention deficit hyperactivity disorder

(ADHD) has an estimated prevalence of 3.4% in adults. In these

patients, symptoms of emotional dysregulation constitute an impor-

tant feature of the disorder. Additionally, comorbidity with affective

disorders, including bipolar disorder, has been reported. The promotor

polymorphism 5-HTTLPR of the serotonin transporter gene has been

implicated in a range of psychiatric disorders. Association has been

reported between the short (S) allele and affective temperaments,

particularly cyclothymic temperament, measured using the Temper-

ament Evaluation of Memphis, Pisa, Paris and San Diego-

autoquestionnaire version (TEMPS-A). The aims of this study were to


123

analyse affective symptoms in adult ADHD patients as compared to

healthy controls, and to explore whether there is an association

between 5-HTTLPR and affective symptoms.

Methods: We studied 534 Norwegian adult ADHD patients and 530

ethnically matched controls. All participants filled out the mood

disorder questionnaire (MDQ), the 21-item cyclothymic subscale of

TEMPS-A and questions concerning lifetime occurrence of other

psychiatric illnesses. The threshold for a positive TEMPS-A score

was defined as C11 questions answered by ‘‘yes’’. For MDQ, a

positive score was defined as ‘‘yes’’ being the answer to C7 out of 13

questions concerning lifetime symptoms of mania and hypomania,

and additionally that the symptoms had co-occurred and resulted in

moderate or severe functional impairment. DNA was extracted from

whole blood or saliva using the OrageneTM DNA Self-Collection Kit

(DNA Genotek Inc., Ontario, Canada). The 5-HTTLPR was amplified

by the polymerase chain reaction (PCR) and genotyped by fragment

analysis on the ABI3100 (Applied Biosystems, Foster City, CA,

USA). The genotypes were automatically called using the GeneM-

apper software (Applied Biosystems), and the results were analysed

using the PLINK software.

Results: On MDQ, the mean scores were 8.1 for the cases (SD = 3.9)

and 2.9 for the controls (SD = 3.2), and on TEMPS-A the scores

were 13.7 for the cases (SD = 5.3) and 5.0 for the controls

(SD = 4.9). When the scales were dichotomised, 50% of the patients

and 6% of the controls scored positive on MDQ, and 73% of the

patients and 15% of the controls scored positive on TEMPS-A

(p \ 0.001 for both scales). The allele frequencies of the 5-HTTLPR

were 42.6% for the S allele, and the genotypes of both patients and

controls were in Hardy–Weinberg equilibrium. The S allele was more

frequent among the cases, but the difference was not significant (OR

1.13, 95% CI 0.95–1.35; p = 0.15).

The 5-HTTLPR showed no association with dichotomised MDQ (OR

1.07, 95% CI 0.88–1.30; p = 0.50) or TEMPS-A (OR 0.99, 95% CI

0.83–1.19; p = 0.93), or on the continuous scales (MDQ: p = 0.62;

TEMPS-A: p = 0.56). Furthermore, no effects were observed when

stratifying by gender or ADHD status.

Discussion: We confirm that self-reported problems of emotional

dysregulation are common in ADHD. A large proportion of patients

scored positive on MDQ and on the cyclothymic scale of TEMPS-A,

and the values of both scales were significantly higher in the patients

than in the controls. The short allele of 5-HTTLPR was slightly, but

not significantly, overrepresented in the patient group. The previously

reported association of 5-HTTLPR with TEMPS-A scores was not

replicated in our samples.

Conclusion: MDQ and TEMPS-A confirm the high load of affective

symptoms in adults with a clinical ADHD diagnosis. Our data,

however, did not support the previously described association

between the serotonin transporter gene polymorphism 5-HTTLPR and

TEMPS-A scores.

Mathematics learning disabilities and children

with ADHD: exploring cognitive commonalties

A. Melia1, A. Miranda2

1University of Miami, Florida, USA; 2University of Valencia,

Valencia, Spain

Introduction and objectives: Literature recognizes a significant

association between ADHD and learning disabilities (LD). However,

knowledge about the relationship between ADHD and LD in math-

ematics (MLD) is still limited. The objective of the study was to

analyse executive functions (EFs) in children with ADHD + MLD.

Methods: A total of 136 children participated (6–14 years old). From

a 2 9 2 design, the sample was divided in four groups depending on

two criteria: ADHD-combined subtype diagnosis based on DSM-IV,

and MLD diagnosis based on discrepancy criteria. The EFs studied

were: energetic resources regulation, inhibitory control and attention,

verbal and visual-spatial working memory.

Results: Results showed a double dissociation between ADHD and

MLD. Deficit in inhibitory control, resources regulation and attention

were explained by the presence of ADHD. However, deficits in

working memory (both verbal and visual-spatial) were better

explained by MLD presence. Children with a profile of

ADHD + MLD showed a combination of deficits from both disorders,

with a trend of higher severity compared to a single disorder profile.

Discussion: ADHD and MLD are characterized by different endo-

phenotypes.

Conclusion: Significant differences on cognitive profiles among

children with ADHD could be due to specific LD comorbidity.

Keywords: ADHD, Mathematics, Learning disabilities, Executive

functions, Endo-phenotype

Anxiety disorders in preschoolers

with and without symptoms of attention deficit

hyperactivity disorder

Kristin Øvergaard1, Pal Zeiner1, Heidi Aase2,the ADHD Project Group1,2

1Oslo University Hospital, Uleval, Norway; 2Division of Mental

Health, Department of Adult Mental Health, Norwegian Institute of

Public Health, Oslo, Norway

Introduction and objective: Attention-deficit/hyperactivity disorder

(ADHD) is a neurodevelopmental disorder characterized by age-

inappropriate levels of inattention, hyperactivity and impulsiveness.

Studies in school age children have shown that about 40% of patients

with ADHD also have comorbid anxiety disorder or a depressive

disorder. So far there is only one study of ADHD comorbidity in

preschoolers [1]. In this study oppositional defiant behaviour medi-

ated the relationships between anxiety and depression, depression and

conduct disorder, and emotional disorders and ADHD. The ongoing

study ‘‘Preschool ADHD: Early characteristics, developmental tra-

jectories, risk, and protective factors in a prospective birth cohort

(The ADHD-study)’’ provides a unique opportunity to study clinical

data on children’s psychiatric symptoms, including the occurrence of

anxiety disorders alone and in combination with other disorders,

ADHD in particular [2].

The question addressed in this presentation is: What is the frequency

of anxiety disorders in preschoolers with symptoms of hyperactivity

and impulsivity? Is the co-occurrence of ADHD and anxiety disorders

mediated through oppositional defiant behaviour? Do other factors

such as dysregulation of emotions, sleep, and sensory stimuli increase

the risk of developing anxiety disorders in preschool children with

ADHD?

Methods: Population based birth cohort design, including a group

design based on screening and clinical assessment. Participants:

About 600 children aged 36–44 months, recruited from the Mother

and Child Cohort Study (MoBa) [3]. Of these, 75% are screened from

the 36 months questionnaire on questions related to symptoms of

ADHD, while 25% are randomly selected. Clinical assessment: It

includes a structured clinical interview with mother, questionnaire

data from parents and teacher, in addition to developmental and

clinical information and a short medical and neurological

examination.


123

Preliminary results: Preliminary analyses of a subset of 438 children

showed that, of children with significant symptoms of ADHD

(*25%) about 30% met criteria for ADHD combined subtype at

either clinical or subthreshold levels; about 67% met clinical or

subthreshold criteria for the ADHD hyperactive/impulsive subtype,

while only 3% met clinical or subthreshold criteria for the ADHD

inattentive subtype.

Symptoms of anxiety at either clinical or subthreshold levels were

found in 16% of the total sample. Of children with significant anxiety

symptoms, almost 40% also had ADHD.

Symptoms of disruptive behaviour disorders at either clinical or

subthreshold levels were found in 40% of the total sample. Dysreg-

ulation of emotions, sleep, or sensory stimuli is identified in more

than 50% of the children.

Discussion: In the group of children that have been clinically eval-

uated so far at the age of 3–4 years of age there is a significant

number of children with symptoms of anxiety disorders. About 40%

of children with symptoms of anxiety disorder also have ADHD.

Further analyses will study differences between children with anxiety

alone, anxiety and ADHD, and anxiety + ADHD + oppositional

behaviour. These data will be presented at the symposium in May.

Conclusion: The preliminary results of the ADHD-study show that

there is an overlap of children with ADHD and anxiety. The nature of

the co-occurrence of these two disorders is poorly understood. The

Preschool ADHD study provides a unique opportunity to study the

occurrence of anxiety disorders alone and in combination with other

disorders; ADHD in particular

References

1. Costello EJ, Egger H, Angold A (2005) 10-year research update

review: the epidemiology of child and adolescent psychiatric

disorders: I. Methods and public health burden. J Am Acad Child

Adolesc Psychiatry 44:972–986

2. Egger HL, Angold A (2006) Common emotional and behavioral

disorders in preschool children: presentation, nosology, and

epidemiology. J Child Psychol Psychiatry 47:313–337

3. Magnus P, Irgens LM, Haug K et al (2006) Cohort profile: the

Norwegian Mother and Child Cohort Study (MoBa). Int J

Epidemiol 35:1146–1150

An investigation of dopamine gene effects

on hypothetical and real-time delay discounting,

and a trait measure of impulsivity, in adolescents

with ADHD and controls

Y. Paloyelis1, M.A. Mehta2, S.V. Faraone3, P. Asherson1, J. Kuntsi1

1MRC SDGP Centre, Institute of Psychiatry, King’s College, London,

UK; 2Centre for Neuroimaging Sciences, Institute of Psychiatry,

King’s College, London, UK; 3Departments of Psychiatry and of

Neuroscience and Physiology, SUNY Upstate Medical University,

Syracuse, NY, USA

Background: Preference for smaller-immediate over larger-delayed

rewards is one of the most widely studied aspects of impulsivity, has

been directly and indirectly linked to dopaminergic neurotransmission

and is consistently observed in ADHD. Previous research in ADHD

has mainly used a paradigm offering repeated choices between fixed

tertiary reinforcers (points) in real-time (see [1] for a review). How-

ever, few studies have examined the interplay between reward

magnitude and delay, using real-time (e.g. [2]) and hypothetical

delay-discounting tasks [3], which are thought to reflect transient

(state) and more enduring (trait) impulsive tendencies, respectively.

Additionally, there is scarce data examining the extent to which such

tendencies can be predicted by variation in dopamine genes.

Method: Thirty-six male adolescents with ADHD-combined subtype

(ADHD-CT) and 32 controls (M = 15.42, SD = 2.05) performed a

real-time and a hypothetical discounting task and provided self-rat-

ings using Barratt’s Impulsiveness Scale. Participants were selected

on the basis of copies of a dopamine transporter haplotype (DAT110/6)

and were genotyped for the COMTval158met and DRD4 48 base-pair

polymorphisms. Separate analyses of covariance were conducted by

task, including all genotypes and covarying for age, IQ and SES, and

significance values were confirmed with permutation testing and

corrected for multiple testing.

Results: ADHD-CT participants reported (p \ 0.001, R2 = 0.20) and

displayed higher impulsivity levels in the hypothetical (p = 0.003,

R2 = 0.08) but not the real-time delay-discounting task compared to

controls. Discounting rates in the ADHD-CT group were only

affected by delay but not reward magnitude. A DAT110/6 9 diagnosis

in the hypothetical discounting task (p = 0.002, R2 = 0.12) showed

that the ADHD-CT group displayed greater impulsivity than controls

only among carriers\2 copies of DAT110/6 (p \ 0.001), and DAT110/

6 homozygotes displayed greater impulsivity than carriers \2 copies

only in the control group (p = 0.002). In the same task, COMT-

val158met met-allele homozygotes showed greater impulsivity than val-

carriers (p = 0.014, R2 = 0.07). DAT110/6 homozygotes rated

themselves as less impulsive than carriers \2 copies (p = 0.01,

R2 = 0.11), while there was a trend for a DAT110/6 9 diagnosis

(p \ 0.10, R2 = 0.03). Discounting rates in the real-time task were

not predicted by genetic variation, and there were no effects for

DRD4.

Discussion/conclusion: Consistent with previous research, adoles-

cents with ADHD-CT (who rated themselves as more impulsive than

controls) displayed greater impulsivity in a hypothetical discounting

task, but did not differ from controls in a real-time task. Variation in

dopamine genes predicted self-ratings of trait impulsivity and

(interacting with diagnosis) performance in the hypothetical dis-

counting task but not the real-time task, indicating that differences in

dopamine genes may affect trait-like impulsive predispositions in

ADHD-CT participants and healthy controls, but not transient

impulsive behaviour. Our data suggests that discounting in ADHD-

CT may be influenced by different processes than in healthy controls,

and is consistent with an extension of the state regulation model to

impulsive decision-making in ADHD-CT. These findings will also be

discussed in the context of neuroimaging data on the effects of var-

iation in dopamine genes on reward-processing in the same sample.

Keywords: ADHD, Delay discounting, Impulsivity, Reward, DAT1,

COMT, DRD4

References

1. Paloyelis Y, Asherson P, Kuntsi J (2009) Are ADHD Symptoms

associated with delay aversion or choice impulsivity? A general

population study. J Am Acad Child Adolesc Psychiatry

48(8):837–846

2. Scheres A, Dijkstra M, Ainslie E, Balkan J, Reynolds B, Sonuga-

Barke E et al (2006) Temporal and probabilistic discounting of

rewards in children and adolescents: effects of age and ADHD

symptoms. Neuropsychologia 44:2092–2103

3. Barkley RA, Edwards G, Laneri M, Fletcher K, Metevia L (2001)

Executive functioning, temporal discounting, and sense of time in

adolescents with attention deficit hyperactivity disorder (ADHD)

and oppositional defiant disorder (ODD). J Abnorm Child

Psychol 29:541–556


123

ADHD and William syndrome: shared behavioural

and neuropsychological profiles

Sinead M Rhodes1*, Deborah M. Riby2, Keith Matthews3,David R. Coghill3

1Department of Psychology, University of Strathclyde, Graham Hills

Building, 40 George Street, Glasgow G1 IQE, UK; 2School of

Psychology, University of Newcastle, Ridley Building 1, Framlington

Place, Newcastle upon Tyne, NE1 7RU, UK; 3Centre for

Neuroscience (Psychiatry and Behavioural Sciences), Division of

Medical Sciences, University of Dundee, Ninewells Hospital and

Medical School, Dundee DD1 9SY, UK

Introduction and objective: Children with the behaviourally defined

disorder ADHD and individuals with the chromosomal disorder

William syndrome (WS) share a similar neuropsychological profile

and the gene SNAP-25 has been implicated in the expression of

both disorders. While there are a number of anecdotal reports in the

literature concerning the similarity of the behaviour of individuals

with ADHD and WS, no study has directly compared the behav-

ioural or neuropsychological profile of the two disorders. Here we

compared the behavioural profile of ADHD and WS with typically

developing controls in relation to parent ratings on the Conners

ADHD behaviour scale and measures of cognitive functioning,

including short-term memory and a range of aspects of executive

functioning.

Methods: Nineteen individuals with WS (mean age 18.4 years), 19

drug naıve children with ADHD (mean age 11.7 years), and 19 typ-

ically developing children (mean age 11.4 years) were matched on

verbal ability (BPVS raw score) and compared on standardized val-

idated tasks from the CANTAB neuropsychological battery. All

participants completed the executive ID/ED attention set-shifting,

Spatial Working Memory (SWM), and Stockings of Cambridge

(SOC) planning tasks and the STM Delayed Matching to Sample task.

Parents of all participating children completed the Conners ADHD

(CPRS) rating scale.

Results: Children with WS and ADHD showed highly similar

behavioural profiles on the CPRS. Like children with ADHD and in

contrast to typically developing controls, children with WS scored

within the abnormal range for oppositionality, cognitive problems/

inattention, hyperactivity subscales and on the ADHD Index and the

clinical groups did not differ in severity of symptoms on these four

measures. Critically, all of the children with WS had scores within the

abnormal range of the ‘ADHD index’. Both groups showed similar

impaired performance in comparison to controls on the executive

attention set-shifting, working memory, and planning tasks, although

the WS group were more severely impaired in their WM and planning

abilities (SWM and SOC tasks). The WS group showed comparable

delay dependent impairment on the DMtS STM task to children with

ADHD.

Conclusion: Despite the clinical and aetiological differences between

ADHD and WS both conditions are characterised by a strikingly

similar behavioural profile of both oppositional behaviour and inat-

tention and hyperactivity. The disorders also share a similar

neuropsychological profile of executive function and STM impair-

ments. These findings may have clinical implications for the

management of individuals with WS.

*Presenting author

Probing mechanisms of hyperactivity and inattention:

Insights from disorders of known genetic origin

Gaia Scerif1*, Victoria Cole1, Elena Longhi1, Kim Cornish2,Annette Karmiloff-Smith3

1Attention, Brain and Cognitive Development, University of Oxford,

Oxford, UK; 2School of Psychology, Psychiatry and Psychological

Medicine, Monash, Australia; 3Birkbeck, University of London,

London, UK

*Presenting author

Contact details: Dr. Gaia Scerif, Department of Experimental

Psychology, University of Oxford, Oxford OX1 3UD, UK; E-mail:

[email protected]

Introduction: A mechanistic understanding of attention deficit

hyperactivity disorder (ADHD) has been greatly advanced by clear

interdisciplinary efforts bridging across genetics, neuroimaging,

cognition, developmental psychology and psychiatry. The proposed

seminar will detail a distinct but complementary approach to under-

standing hyperactivity and inattention: their investigation in

individuals with developmental disorders of known genetic origin. In

particular, and as a case in example, here we focus on fragile X

syndrome (FXS), a monogenic disorder associated with striking

inattention and hyperactivity even in early childhood [3]. At the

genetic and molecular level, FXS depends on the silencing of a single

X-linked gene (Fragile X Mental Retardation-1 gene, FMR-1) whose

protein product is involved in experience-dependent changes at

metabotropic glutamatergic synapses across cortex and subcortical

areas. The causative mutation also interacts with dopaminergic

modulation and this, in turn, suggests that FXS may be a very useful

model to inform the neurocognitive mechanisms underpinning

attentional control difficulties in more aetiologically heterogeneous

groups such as ADHD. However, hitherto attentional difficulties in

FXS have been studied as static snapshots in development, calling for

a greater understanding of how these change over time. In addition,

and of clinical relevance, clear attentional deficits at the group level in

boys with FXS are also accompanied by variability in outcome, with

some boys with full mutation status nonetheless experiencing limited

inattention and hyperactivity. The current study investigates the

impact of FXS on early developmental trajectories of sustained

attention and inhibitory control. A longitudinal design aims to pin-

point the factors predicting individual differences in improvement or

stability of these difficulties.

Methods: The data presented here are part of a larger 3-year longi-

tudinal study of attentional processes in boys with fragile X syndrome

(N = 59, age range 3–10 years at Time 1) and typically developing

boys (N = 129, age range 3–10 years), now in its third and final year.

All children took part in experimental tasks tapping multiple pro-

cesses that could contribute to attentional difficulties (from simple

perceptual processing to dealing with multimodal stimuli). Here, we

report on three tasks designed to test children’s ability to sustain

attention and detect infrequent targets (oddball tasks), and on two

tasks assessing their inhibitory control difficulties (speeded go-nogo

tasks), while controlling for potential low-level perceptual processing

differences across groups. Children also engaged in the standardised

assessment of their nonverbal intelligence (Leiter international per-

formance scale) complemented by parental and teacher reports (for

the purposes of this seminar, limited to Conners’ behaviour rating


123

scales, strengths and difficulties questionnaire). Finally, genotyping

and information on the children’s environment aimed at isolating

specific factors moderating the effects of FMR-1 gene silencing and

resulting in better cognitive outcome. Here we report on two longi-

tudinal time-points, 1 year apart.

Results: At the group level and at each developmental time-point,

children with FXS exhibited greater difficulties in sustained attention

and inhibitory control than expected given their developmental level.

Children with FXS missed many more targets when required to sus-

tain attention, and failed to achieve the required balance between

response and restraint that is critical to achieving effective inhibitory

control. However, investigating longitudinal changes also revealed

great individual differences in the extent to which either attentional

deficit remained stable or improved. Hypothesised gene–gene and

gene–environment interactions predicting better outcome in terms of

inattention and hyperactivity are currently being investigated.

Discussion: Findings suggest that even in disorders associated with

single genetic dysfunctions such as FXS, it is incorrect to assume

a priori that genotype–cognitive phenotype relations result in selec-

tively spared or impaired attentional processes and that the pattern of

deficits is necessarily stable over developmental time. Parallels are

drawn with our ongoing studies of attentional difficulties in other

developmental disorders of known genetic origin. We believe that

developmental change and stability of sustained attention and inhib-

itory difficulties in these samples highlight the implications of taking

developmental processes seriously disorders characterised by high

heritability but as yet unidentified genetic correlates, such as ADHD.

Conclusion: We conclude by arguing that efforts should be dedicated

to operationalising precisely why and how early changes in neuro-

computational properties (be they related to dopaminergic functions,

to an underlying glutamatergic substrate or to other factors) may have

greater impact on certain aspects of attentional control [2], and to

testing empirically patterns of stability and change over develop-

mental time [1]. Furthermore, studying individual variability in

developmental trajectories may provide a window into understanding

how gene–gene and gene–environment interactions modulate symp-

toms of hyperactivity and inattention.

Keywords: Inattention, Hyperactivity, Neural mechanisms, Devel-

opment, Genetic disorders

References

1. Scerif G, Cornish K, Karmiloff-Smith A (2010) Attention and

social cognition at the crossroads: Having genetic disorders lead

the way. Trends Cogn Sci (in review)

2. Scerif G, Cornish K, Wilding J, Driver J, Karmiloff-Smith A

(2007) Delineation of early attentional control difficulties in

fragile X syndrome: focus on neurocomputational mechanisms.


3. Scerif G, Karmiloff-Smith A, Campos R, Elsabbagh M, Driver J,

Cornish K (2005) To look or not to look? Typical and atypical

development of oculomotor control. J Cogn Neurosci 4:591–604

Low-frequency neuronal oscillations show evidence

of heritability and association with performance

measures in ADHD

Charlotte Tye1, Fruhling Rijsdijk1, Jonna Kuntsi1, Philip Asherson1,Patrick Bolton1, Grainne McLoughlin1

1MRC SGDP Centre, Institute of Psychiatry, King’s College, London,

UK

Introduction and objective: Increased reaction-time variability

(RTV) in ADHD may arise from the inability to appropriately

modulate very low-frequency oscillations (VLFOs; \0.05 Hz) of the

brain that are observed when the brain is in ‘default-mode’. A lack

of sufficient VLFO attenuation or ‘default-mode interference’ during

cognitive activity may play a role in attentional lapses that con-

tribute to RTV [3]. Recent studies using EEG to investigate this

hypothesis have reported an association between reduced VLFO

power and inattention symptom scores and that less rest-to-task

VLFO attenuation is associated with ADHD [1]. State-related con-

ditions can affect the transition; if the individual is experiencing

little extrinsic motivation, VLFO attenuation would require a larger

investment of energetic resources [3]. Therefore it can be hypoth-

esised that default-mode interference in ADHD would decrease

when the individual is offered a reward, as extrinsic motivation

increases and arousal is optimised. EEG frequency bands consis-

tently demonstrate high heritability, an important criterion for its

acceptance as a marker of a disorder, yet this has not yet been

investigated in VLFOs. An additional aim of the study is to

investigate heritability and genetic overlap between ADHD and

VLFOs.

Methods: 68 twin pairs were recruited from the twins early devel-

opment study (TEDS) based on a trajectory analysis of consistently

high or low ADHD scores. The fast task [2], a four-choice reaction

time task, was administered to measure the effects of arousal con-

sisting of a baseline and a fast-incentive condition combining a fast

event rate and rewards. VLFO activity was measured using DC-EEG.

Mean absolute power was calculated using fast-Fourier transform

(FFT) analysis across sub-delta very low-frequency bands Slow-4

(S4; 0.02–0.06 Hz), Slow-3 (S3; 0.06–0.2 Hz), Slow-2 (S2; 0.2–

0.5 Hz) and Slow-1 (S1; 0.5–1.5 Hz). We will apply structural

equation model-fitting using monozygotic (MZ) and dizygotic (DZ)

twin pairs ascertained on ADHD scores. The program Mx will be

used for maximum likelihood genetic model fitting, using an applied

bivariate model, to directly estimate model parameters [additive

genetic (A); common environmental (C); and unique environmental

effects (E)] from the observed data.

Results: Based on previous research (Helps et al. 2010), we combined

S4 + S3 and S2 + S1. Preliminary analysis of 60 twin pairs during the

completion of the baseline condition of the Fast task suggests sig-

nificantly higher S3 + S4 power in those with high symptoms scores

(M = 0.7140, SD = 1.90) compared to those with low symptom

scores (M = -0.3275, SD = 1.74; t = -2.12, p \ 0.05). Addition-

ally, significant associations were found between S3 + S4 and mean

reaction-time (MRT; r = 0.307, p \ 0.05) and reaction-time standard

deviation (RTSD; r = 0.397, p \ 0.01), and between S1 + S2 and

MRT (r = 0.376, p \ 0.01) and RTSD (r = 0.283, p \ 0.05). We

will report VLFO patterns during the fast-incentive and rest condi-

tions to assess the effect of arousal on default-mode interference. We

will further describe the genetic models for VLFOs based on model-

fitting analyses.

Discussion: The findings support previous studies reporting increased

VLFO power during cognitive activity in ADHD, suggesting that

during task completion those with ADHD have increased default-

mode interference. Moreover, decreased attenuation of VLFOs during

cognitive activity is associated with poor task performance. The

implications of heritability will be discussed.

Conclusion: These findings strengthen the association between non-

optimal arousal and inattention, and warrant further investigation of

the state-related factors that may improve task performance and EEG-

indexed arousal using genetically sensitive designs.

References

1. Helps SK, Broyd SJ, James CJ, Karl A, Chen W, Sonuga-Barke

EJS (2010) Altered spontaneous low frequency brain activity in

attention deficit hyperactivity disorder. Brain Res (in press)

2. Kuntsi J, Andreou P, Ma J, Borger NA, van der Meere JJ (2005)

Testing assumptions for endophenotype studies in ADHD:


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reliability and validity of tasks in a general population sample.

BMC Psychiatry 5:40

3. Sonuga-Barke EJ, Castellanos FX (2007) Spontaneous attentional

fluctuations in impaired states and pathological conditions: a

neurobiological hypothesis. Neurosci Biobehav Rev 31:977–986

Neurocognitive dysfunction in children with ADHD:

impact of comorbidity and differential diagnostic

aspects

Timo D. Vloet1,2, Beate Herpertz-Dahlmann1, Kerstin Konrad2,Stephane A. De Brito3, Georg G. Polier1, Ivo Marx4,Berrak Kahraman-Lanzerath2, Florian D. Zepf1, Thomas Gunther1

1Department of Child and Adolescent Psychiatry, Medical Faculty,

RWTH Aachen University, Aachen, Germany; 2Child

Neuropsychology Section, Department of Child and Adolescent

Psychiatry, Medical Faculty, RWTH Aachen University, Aachen,

Germany; 3Developmental Risk and Resilience Unit, Division of

Psychology and Language Sciences, Research Department of Clinical

Educational and Health Psychology, University College London,

London, UK; 4Department of Psychiatry and Psychotherapy,

University of Rostock, Rostock, Germany

Introduction and objective: In clinical practice, neuropsychological

measurements are frequently chosen to assess attention problems in

children. However, there is still a paucity of data from children with

attention-deficit hyperactivity disorder (ADHD) and especially

comorbid internalizing disorders. In addition, disorder-specific neu-

ropsychological dysfunctions of ADHD and etiologically related

neurodevelopmental disorders like obsessive–compulsive disorders

(OCD) are still unclear. We present data from three different

investigations.

Methods: (1) Children with ADHD, comorbid anxiety disorders

(ANX) and healthy controls (HC) (n = 34 for each group, all aged 8–

15 years) participated in five neuropsychological tasks (alertness,

sustained-attention, divided-attention, go/nogo and set-shifting). (2)

The same test-battery was completed by children with ADHD,

comorbid depressive disorders (DD), pure DD and HC (n = 64 for

each group, all aged 10–15 years). (3) Finally, two neuropsycholog-

ical tasks were applied that tap into different functions associated with

the cortico-striato-thalamo-cortical-circuitry (CSTCC), namely a

serial-reaction-time (SRT) task (implicit-sequence-learning) and a

delay-aversion (DA) task (abnormal motivational processes). Data of

boys with ADHD (n = 20), OCD (n = 20) and HC (n = 25), all aged

10–18 years, were compared.

Results: Performance in sustained-attention and selective-attention

tasks of children with ADHD + ANX was better than that of children

with ADHD only. Children with ADHD, ADHD + DD and DD only

were all characterized by attentional problems, especially in the more

complex attentional tasks and the intensity aspects of attention. While

children with ADHD were characterized by DA and children with

OCD showed impaired implicit-learning, the ADHD-group was

unimpaired in their implicit-learning behavior and the OCD-group

was not characterized by a DA-style.

Discussion: Results indicate that ADHD + ANX might constitute a

cognitively distinct subtype. Differences between ADHD, DD and

ADHD + DD could be detected, but the neuropsychological effects

were not strong enough to differentiate clinical groups. The double

dissociation between ADHD and OCD highlights distinct cognitive

dysfunctions associated with both disorders and might point to dif-

ferent neural abnormalities within the CSTCC.

Conclusions: The identification of disorder-specific neuropsycho-

logical dysfunction might be helpful for further our understanding of

the underlying pathophysiology in ADHD and related disorders and

could also be adjuvant for treatment considerations.

ADHD in children and adolescents: examination

of the contribution of irritability, sadness and anxiety

to working memory problems

J. Winther1,2, S. Aggarwal1,2, K. Rennie1,2, C. Prakash1,2, A. Vance1,2

1Developmental Neuropsychiatry Program, Department of

Paediatrics, University of Melbourne, Royal Children’s Hospital,

Melbourne, Australia; 2Murdoch Childrens Research Institute;

University of Melbourne, Melbourne, Australia

Objective: ADHD is known to be associated with increased symp-

toms of anxiety, irritability and sadness. Currently, it is unknown

whether these three common symptoms independently contribute to

working memory problems aside from core ADHD symptoms.

Methods: A large cross sectional study of children and adolescents

with categorically and dimensionally defined ADHD (N = 1,150).

Results: Only core ADHD and sadness/unhappiness symptoms made

independent significant contributions to the prediction of spatial

working memory deficits. Only core ADHD and irritability symptoms

made independent significant contributions to the prediction of

strategy deficits. In contrast, core ADHD, irritability and sadness/

unhappiness symptoms made independent significant contributions to

the prediction of spatial span deficits. Importantly, while core ADHD

symptoms were associated with worsening spatial working memory,

strategy and spatial span performance, irritability and sadness/

unhappiness were associated with better performance of these mea-

sures. Anxiety made no independent contribution and there was no

shared contribution of anxiety, irritability and sadness/unhappiness to

the variance of spatial working memory, strategy and spatial span

performance.

Conclusion: As expected, core ADHD symptoms are associated with

worse working memory performance in children and adolescents with

ADHD while surprisingly sadness/unhappiness and irritability are

associated with better working memory performance. Clinical and

research implications are explored.


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Chronaki, Georgia, Garner Matthew, Hadwin, Julie, Sonuga-Barke, Edmund J.S. and Broyd, Samantha J. (2010). Electrophysiological correlates of emotion processing in children with ADHD.

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