Autism Spectrum Disorders: Challenges and Opportunitiespediatricnursing.net/conf/handouts/2010/Session_214_Souders.pdf · Autism Spectrum Disorders: Challenges and Opportunities Margaret

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Autism Spectrum Disorders:Autism Spectrum Disorders:Challenges and Opportunities Challenges and Opportunities

Margaret C. Souders PhD, CRNPMargaret C. Souders PhD, CRNPPediatric Nurse Practitioner Pediatric Nurse Practitioner

The ChildrenThe Children ’’s Hospital of Philadelphias Hospital of PhiladelphiaCenter for Autism ResearchCenter for Autism Research

University of Pennsylvania, CADDREUniversity of Pennsylvania, CADDREPost Doctoral Fellow Schools of Medicine/Nursing Post Doctoral Fellow Schools of Medicine/Nursing

Center for SleepCenter for SleepPENN

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Autism Spectrum DisordersAutism Spectrum Disorders

�� EpidemiologyEpidemiology�� DefinitionDefinition�� Clinical features Clinical features �� Screening and Screening and

diagnosisdiagnosis�� Behavioral TreatmentBehavioral Treatment�� PharmacologyPharmacology�� Family SupportFamily Support

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ObjectivesObjectives

�� Define the core deficits of ASDDefine the core deficits of ASD

�� Discuss early screening, assessment toolsDiscuss early screening, assessment tools��

�� Discuss Evidence Based Treatments Discuss Evidence Based Treatments including Psychopharmacologyincluding Psychopharmacology

�� Identify strategies for supporting the child Identify strategies for supporting the child with an ASD and their familywith an ASD and their family

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EpidemiologyEpidemiology

�� Prevalence 1 in 110 in US, CDC 2010Prevalence 1 in 110 in US, CDC 2010�� Prevalence 1 in 94 in New JerseyPrevalence 1 in 94 in New Jersey

�� CDC 2007CDC 2007�� Higher in males [4Higher in males [4--5 times higher]5 times higher]�� Recurrence risk 3Recurrence risk 3--15% 15%

��1515--20 times higher20 times higher�� Only ~10Only ~10--15% with identified etiology15% with identified etiology

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Autism Spectrum DisordersAutism Spectrum Disorders((DSMDSM--IVIV--TR, 2000TR, 2000))

299.00 Autistic Disorder 299.00 Autistic Disorder

299.80 Rett Disorder 299.80 Rett Disorder

299.10 Childhood Disintegrative Disorder 299.10 Childhood Disintegrative Disorder

299.80 Asperger's Disorder 299.80 Asperger's Disorder

299.80 Pervasive Developmental Disorder 299.80 Pervasive Developmental Disorder

Not Otherwise SpecifiedNot Otherwise Specified

(PDD(PDD--NOS)NOS)

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AUTISTIC SPECTRUM DISORDERSAUTISTIC SPECTRUM DISORDERSLevy 2001Levy 2001

ChildhoodDisintegrative

Disorder

ASPERGER’SDisorder

PDD-NOS

AUTISM[Classical]

Core Deficits

Socialization

Communication

Behavior

Increased Severity

CommunicationDisordersLD [V & NV]ADHDOCDSensoryIntegrative Dysfn

RETT’SDisorder

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Autism Spectrum DisordersAutism Spectrum Disorders

Core DeficitsCore Deficits

�� SocializationSocialization

�� CommunicationCommunication

�� Repetitive/ stereotypic behaviorRepetitive/ stereotypic behavior

�� Deviant relative to developmental levelDeviant relative to developmental level

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Definition of ASDDefinition of ASD

�� Qualitative impairment in socializationQualitative impairment in socialization�� nonverbal behaviors, peer relationships, social reciprocity nonverbal behaviors, peer relationships, social recip rocity

(giving, showing, social smiles, gestures, eye contac t)(giving, showing, social smiles, gestures, eye contac t)

�� Deficits in communicationDeficits in communication�� delay/ unusual/ absent spoken language; absent delay/ unusual/ absent spoken language; absent

imaginative play imaginative play

�� Repetitive/ stereotypic behaviorRepetitive/ stereotypic behavior�� stereotypy, perseverations, rigidity, routinesstereotypy, perseverations, rigidity, routines

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What is CADDRE?What is CADDRE?

�� PIPI--Jennifer PintoJennifer Pinto--Martin PhDMartin PhD-- EpidemiologistEpidemiologist

�� Center for Autism and Developmental Disabilities Center for Autism and Developmental Disabilities Research and Epidemiology Research and Epidemiology --CDC Funding (2001 CDC Funding (2001 --2010)2010)

�� StudiesStudies�� Screening for Early Detection of AutismScreening for Early Detection of Autism

�� Prevalence of ASDPrevalence of ASD--Surveillance (1:150, 2007) PASurveillance (1:150, 2007) PA

�� Study Exploration of Early Development (SEED)Study Exploration of Early Development (SEED)

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CADDREs in CDC NetworkCADDREs in CDC Network

�� PennsylvaniaPennsylvania

�� Maryland/DEMaryland/DE

�� CaliforniaCalifornia

�� ColoradoColorado

�� North CarolinaNorth Carolina

�� GeorgiaGeorgia

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Who should be screened?Who should be screened?

American Academy of Pediatrics:American Academy of Pediatrics:

•• Developmental surveillance at every wellDevelopmental surveillance at every well--child visit child visit (age 21 years) + (age 21 years) + •• Formal screening at 9 months, 18 months, 30 monthsFormal screening at 9 months, 18 months, 30 months•• Formal autism screening at 18 months and 24 monthsFormal autism screening at 18 months and 24 months•• School readiness screening at 4 year old well visitSchool readiness screening at 4 year old well visit

•• Developmental screening using formal, validated Developmental screening using formal, validated tools at 9, 18 & 30 months or whenever concern is tools at 9, 18 & 30 months or whenever concern is expressedexpressed

AAP. ( 2006). AAP. ( 2006). Pediatrics, 118Pediatrics, 118 (1), 405(1), 405--420.420.Johnson & Myers. Johnson & Myers. (2007). (2007). Pediatrics, 120Pediatrics, 120 (5), 1183(5), 1183--1215.1215.

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Improving Developmental ScreeningImproving Developmental ScreeningPractices and Early Identification of Autism in Practices and Early Identification of Autism in

PennsylvaniaPennsylvania

Presented by:Presented by:Frances P. Glascoe, Ph.D.Frances P. Glascoe, Ph.D.

Department of PediatricsDepartment of PediatricsVanderbilt UniversityVanderbilt University

Margaret C. Souders PhD CRNPMargaret C. Souders PhD CRNPThe ChildrenThe Children’’s Hospitals Hospital

of Philadelphiaof Philadelphia

Jennifer PintoJennifer Pinto--Martin PhDMartin PhDUniversity of PennsylvaniaUniversity of Pennsylvania

Nancy D. WisemanNancy D. WisemanFirst Signs, Inc.First Signs, Inc.

© 2004 First Signs, Inc.; Frances Glascoe, Ph.D. All rights reserved.

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Rett Disorder: Rett Disorder: Regression at 12Regression at 12--18months18months

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Rett Disorder: Rett Disorder: Regression at 30Regression at 30--36 months36 months

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AutismAutism

�� Classical Autism Classical Autism described by described by

�� Dr. Leo Kanner Dr. Leo Kanner �� in 1943in 1943

�� At severe range of the At severe range of the spectrumspectrum

�� Higher coHigher co--existenceexistence�� mental retardationmental retardation�� genetic or other genetic or other

neurological disordersneurological disorders

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Identical Twins: Who has Autistic Identical Twins: Who has Autistic Spectrum Disorder and who has Spectrum Disorder and who has

typical development?typical development?

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Identical Twins? Identical Twins? Who has Autism and Who has Autism and who has Asperger Disorderwho has Asperger Disorder ??

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Clinical FeaturesClinical Features

�� Cognitive abnormalities Cognitive abnormalities �� Uneven profile, Mental Retardation 30Uneven profile, Mental Retardation 30 --75% 75%

�� Gastrointestinal problems (15Gastrointestinal problems (15 --40%)40%)�� Loose stoolLoose stool�� ConstipationConstipation�� Severe food selectivitySevere food selectivity

�� Sleep Disturbances (40Sleep Disturbances (40 --80%)80%)�� InsomniaInsomnia -- prolonged sleep latency, early risings prolonged sleep latency, early risings �� ParsomniasParsomnias --teeth grinding, bed wetting, night teeth grinding, bed wetting, night

terrorsterrors

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Clinical FeaturesClinical Features

�� Seizures (25Seizures (25 --35%)35%)

�� Tic Disorders (9%)Tic Disorders (9%)

�� Mood abnormalities: depression, Mood abnormalities: depression, irritability, anxiety (25irritability, anxiety (25 --40%)40%)

�� ADHD (30ADHD (30--75%)75%)�� SelfSelf --injuryinjury

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Clinical FeaturesClinical Features

�� Sensory Integration DysfunctionSensory Integration Dysfunction�� VisualVisual

�� AuditoryAuditory�� TactileTactile

�� GustatoryGustatory�� OlfactoryOlfactory

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Genetics of AutismGenetics of Autism

�� Familial cases are substantially more frequent. Familial cases are substantially more frequent. Sibling studies suggest 10Sibling studies suggest 10 --20% recurrence rate 20% recurrence rate Landau, Patterson, 2007Landau, Patterson, 2007

�� Monozygotic twins (60Monozygotic twins (60 --91%) Bailey et al, 199591%) Bailey et al, 1995�� Rett Syndrome MECP2 Rett Syndrome MECP2 ––X chromosomeX chromosome�� Fragile X Fragile X –– synaptic gene regulation, 90% ASD synaptic gene regulation, 90% ASD

(Lord,2006)(Lord,2006)�� Tuberous sclerosis Tuberous sclerosis --TSC1/TSC2TSC1/TSC2�� NeurofibromatosisNeurofibromatosis ——NF1NF1�� 22q11.2 deletion22q11.2 deletion -- 20% with ASD features and 25% 20% with ASD features and 25%

with schizophreniawith schizophrenia

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Genetics of AutismGenetics of Autism

�� Neuroligins synaptic genes NLGN3 and NLGN4 Neuroligins synaptic genes NLGN3 and NLGN4 �� cell adhesion molecules role of formation of function al cell adhesion molecules role of formation of function al

synapses, X chromosome.synapses, X chromosome.

�� SHANK 3, scaffolding protein of post synaptic SHANK 3, scaffolding protein of post synaptic density,density, chromosome 22chromosome 22

�� Neurexins NRXN, presynaptic glutamatergic Neurexins NRXN, presynaptic glutamatergic synapse, synapse, Chromosome 2p16, 11Chromosome 2p16, 11

�� Single gene mutations, de novo Copy number Single gene mutations, de novo Copy number variants, and common variant SNPS variants, and common variant SNPS

�� Cadherins, chromosome 5 Ubiquitin pathwaysCadherins, chromosome 5 Ubiquitin pathways

�� Jamain et al, 2003, Jacquemont et al , Sebat, et al 2 007, Jamain et al, 2003, Jacquemont et al , Sebat, et al 2 007, Bourgeron, 2007 Hakonarson, 2009, 2010 Bourgeron, 2007 Hakonarson, 2009, 2010 PENN

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SynapseSynapse

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Synaptic cleftSynaptic cleft

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Fragile X Syndrome: InheritanceFragile X Syndrome: Inheritance

�� XX--linked disorderlinked disorder

�� Both males and females can be affected or normal Both males and females can be affected or normal carrierscarriers

�� Expansion of DNA insertion (CGG triplet repeat)Expansion of DNA insertion (CGG triplet repeat)

�� Normal carrier 25Normal carrier 25--200200

�� Affected >200Affected >200

�� Amplification of triplet repeat in successive Amplification of triplet repeat in successive generationsgenerations

�� Reversible in mice 2008, MITReversible in mice 2008, MIT

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Fragile X Syndrome: Dysmorphic Fragile X Syndrome: Dysmorphic FeaturesFeatures

�� MacrocephalyMacrocephaly�� Prominent jaw (becomes Prominent jaw (becomes

evident in adolescence)evident in adolescence)�� Large, cupped, low set earsLarge, cupped, low set ears�� Long faciesLong facies�� Increased joint flexibilityIncreased joint flexibility�� Large testes (often not present Large testes (often not present

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Tuberous SclerosisTuberous Sclerosis

�� Speech Language delaysSpeech Language delays

�� Behavioral problems Behavioral problems

�� PDD in 60% of affected childrenPDD in 60% of affected children

�� Epilepsy in all cases with dual Epilepsy in all cases with dual diagnosisdiagnosis

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Facial angiofibromas Shagreen patch

A tuber and subependymal nodules Ash leaf spot

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Is there a neurobiological basis for Is there a neurobiological basis for disturbed sleep in children with ASD?disturbed sleep in children with ASD?

�� Serotonergic AbnormalitiesSerotonergic Abnormalities : :

High levels of anxiety, fears and arousal High levels of anxiety, fears and arousal levels (serotonin, 5HT2,3)levels (serotonin, 5HT2,3)(Anderson, 2002, Rapin & Katzman, 1998)(Anderson, 2002, Rapin & Katzman, 1998)

�� Dopaminergic pathwaysDopaminergic pathways : :

PSGPSG-- increased level of muscle twitching, increased level of muscle twitching, muscle activity during REM, PLMSmuscle activity during REM, PLMS(Diomendi et al, 1999, Thirumalai, 2002)(Diomendi et al, 1999, Thirumalai, 2002)

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Is there neurobiological basis for Is there neurobiological basis for disturbed sleep in children with ASD?disturbed sleep in children with ASD?

�� Social Timing and Clock Genes MutationsSocial Timing and Clock Genes Mutations ::�� Core deficits of ASD involving temporal synchrony and social Core deficits of ASD involving temporal synchrony and social

timing timing �� genetic linkagegenetic linkage -- 2q in autism, 2q37 codes for circadian 2q in autism, 2q37 codes for circadian

rhythm gene Hper in Humans (Wolff, et al 2002,Wimpory , rhythm gene Hper in Humans (Wolff, et al 2002,Wimpory , Nicholas & Nash, 2002, Nicholas, et al,2007)Nicholas & Nash, 2002, Nicholas, et al,2007)

�� Two clock gene variants Per1 and Npsa2 have been Two clock gene variants Per1 and Npsa2 have been associated with ASD cohort AGRE (Nicholas, et al, 20 07) associated with ASD cohort AGRE (Nicholas, et al, 200 7)

�� Abnormal Melatonin RhythmAbnormal Melatonin Rhythm�� Late peak and low amplitude (Nir, et al 1995, Patzhol d et al 199Late peak and low amplitude (Nir, et al 1995, Patzhol d et al 199 8, Tordjman, 8, Tordjman,

2005, Andrews,2008). 2005, Andrews,2008). �� There is emerging data involving the role melatonin p lays in There is emerging data involving the role melatonin p lays in

ASD and the efficacy of exogenous melatoninASD and the efficacy of exogenous melatonin

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Biology of AutismBiology of Autism

�� The Role of the fusiform face area (FFA) in social The Role of the fusiform face area (FFA) in social cognition: Implications for the pathobiology of cognition: Implications for the pathobiology of autism. The Royal Society, 415autism. The Royal Society, 415 --427. (2003) Schultz, 427. (2003) Schultz, Child Study Center, Yale UniversityChild Study Center, Yale University

�� Specialized Face Region of the right hemisphere. Specialized Face Region of the right hemisphere.

�� Neuro functional markerNeuro functional marker -- hypoactivation of the FFAhypoactivation of the FFA

�� Function MRIFunction MRI -- five studies five studies ––children and adults with children and adults with ASD reduced activity to images of the human face.ASD reduced activity to images of the human face.

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What can nurses do? ScreenWhat can nurses do? Screen

�� Early Warning SignsEarly Warning Signs�� No Big Smiles or warm joyful expressions No Big Smiles or warm joyful expressions

by 6 monthsby 6 months

�� No back and forth sharing by 9No back and forth sharing by 9

�� No babbling by 12 monthsNo babbling by 12 months

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Screen!!Screen!!

�� No gestures by 18 months No gestures by 18 months �� pointing, waving, nodding, giving, showingpointing, waving, nodding, giving, showing

�� No words by 16 monthsNo words by 16 months

�� No two word phrases by 24No two word phrases by 24 months, meaningful months, meaningful phrasesphrases

�� Loss of skills at any age!!!!! Loss of skills at any age!!!!!

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Early Warning Signs: BehaviorEarly Warning Signs: Behavior

�� Severe prolonged Severe prolonged tantrumstantrums

�� Uncooperative or Uncooperative or oppositionaloppositional

�� DoesnDoesn ’’t know how to t know how to play with toysplay with toys

�� Gets stuck on things Gets stuck on things over and overover and over

�� Persistent toePersistent toe --walkingwalking�� Unusual attachments to Unusual attachments to

parts of toys or objectsparts of toys or objects�� Lines things upLines things up�� Odd movement patternsOdd movement patterns�� Extremely oversensitive Extremely oversensitive

to certain textures or to certain textures or soundssounds

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Modified Checklist for Autism Modified Checklist for Autism in Toddlers (MCHAT)in Toddlers (MCHAT)

�� Checklist for Autism in Toddlers/Modified Checklist for Autism in Toddlers/Modified CHAT CHAT

�� Screen @ 18 months / 24 months in primary Screen @ 18 months / 24 months in primary care settingcare setting

�� CHAT: 9 questions/ 5 observations pointing, CHAT: 9 questions/ 5 observations pointing, pretend play, joint attentionpretend play, joint attention

�� MCHAT: 23 questions (parent report)MCHAT: 23 questions (parent report)�� No observations( Robbins, Fine , Barton, 1999)No observations( Robbins, Fine , Barton, 1999)�� Free Google, forms available Free Google, forms available

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Advantages of Early DiagnosisAdvantages of Early Diagnosis

�� Earlier educational planning & treatmentEarlier educational planning & treatment

�� Family supports and trainingFamily supports and training

�� Reduce family stress and Reduce family stress and ““ shoppingshopping ””

�� Delivery of appropriate medical careDelivery of appropriate medical care -- sleepsleep

�� Identify & treat target behaviors which interfere with Identify & treat target behaviors which interfere wit h progressprogress

�� Improved outcomes Improved outcomes ––function, behavior, language function, behavior, language

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Clinical EvaluationClinical Evaluation

�� Hearing testHearing test�� Speech/language EvaluationSpeech/language Evaluation�� Occupational/ Sensory Evaluation: Occupational/ Sensory Evaluation:

gross and fine motorgross and fine motor�� Psychological EvaluationPsychological Evaluation�� Diagnostic ToolsDiagnostic Tools

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Autism Diagnostic Observation Autism Diagnostic Observation Schedule (ADOS)Schedule (ADOS)

�� SemiSemi --structured observational assessment structured observational assessment based on developmental language agebased on developmental language age

�� InvestigatorInvestigator --directed activities to evaluate directed activities to evaluate �� CommunicationCommunication�� Reciprocal social interactionReciprocal social interaction�� PlayPlay�� Sstereotypic behavior and unusual interestsSstereotypic behavior and unusual interests

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What behaviors are we evaluating What behaviors are we evaluating under each category of the DSMunder each category of the DSM--IV?IV?�� Social Interaction (ADOS)Social Interaction (ADOS)

�� Amount of eye contactAmount of eye contact�� Facial expressions (multiple by 12 mo.)Facial expressions (multiple by 12 mo.)�� Shared enjoyment in interactions (by 4 mo.)Shared enjoyment in interactions (by 4 mo.)�� Showing (by 12 mo.)Showing (by 12 mo.)�� Spontaneous initiation of joint attentionSpontaneous initiation of joint attention�� Response to joint attentionResponse to joint attention�� Quality of social overturesQuality of social overtures

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What behaviors are we evaluating What behaviors are we evaluating under each category of the DSMunder each category of the DSM--IV?IV?

�� Communication (ADOS)Communication (ADOS)

�� Frequency of vocalizations directed to othersFrequency of vocalizations directed to others�� Stereotyped/idiosyncratic use of wordsStereotyped/idiosyncratic use of words�� Unusual vocal qualityUnusual vocal quality�� Use of otherUse of other’’s body to communicates body to communicate�� ConversationConversation�� Pointing (by 12 months)Pointing (by 12 months)�� Gestures (by 12 months)Gestures (by 12 months)

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What behaviors are we evaluating What behaviors are we evaluating under each category of the DSMunder each category of the DSM--IV?IV?

�� Repetitive/Stereotypic BehaviorRepetitive/Stereotypic Behavior

�� Unusual sensory interests in play material or Unusual sensory interests in play material or personperson

�� Hand and finger and other complex Hand and finger and other complex mannerismsmannerisms

�� SelfSelf--injurious behaviorinjurious behavior

�� Unusually repetitive interests or stereotyped Unusually repetitive interests or stereotyped behaviorsbehaviors

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Treatments: Treatments: ““ StandardStandard ””

�� EducationalEducational -- small class size small class size ––�� Individual Education PlanIndividual Education Plan�� BehavioralBehavioral

�� Applied Behavior Analysis/ Discrete Trial Applied Behavior Analysis/ Discrete Trial Instruction, Floor TimeInstruction, Floor Time

�� Speech/Language Therapy: Intensive PECS ( Picture Speech/Language Therapy: Intensive PECS ( Picture Exchange Communication System )Exchange Communication System )

�� Occupational TherapyOccupational Therapy -- sensory integrationsensory integration --IntensiveIntensive

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Educational TreatmentEducational Treatment

�� Educating Children Educating Children with Autismwith Autism�� www.nap.eduwww.nap.edu

�� Early & intensive Early & intensive [>25 h/week][>25 h/week]

�� Objective Objective assessmentassessment

�� CurriculaCurricula�� Skill generalization Skill generalization

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Behavioral Treatments Behavioral Treatments

�� APPLIED BEHAVIORAL ANALYSIS (ABA)APPLIED BEHAVIORAL ANALYSIS (ABA)B.F. Skinner 1954B.F. Skinner 1954

�� DISCRETE TRIAL (DDISCRETE TRIAL (DIvar LovaasIvar Lovaas

�� GREENSPAN GREENSPAN ““ FLOOR TIMEFLOOR TIME””Stanley GreenspanStanley Greenspan

�� APPLIED VERBAL BEHAVIORAPPLIED VERBAL BEHAVIORCarbone, Partington, SunbergCarbone, Partington, Sunberg

�� SOCIAL STORIES SOCIAL STORIES Carol GrayCarol Gray

�� COGNITIVE BEHAVIORAL THERAPYCOGNITIVE BEHAVIORAL THERAPY

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Token EconomiesToken Economies

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Speech/language TherapySpeech/language Therapy

�� PrinciplesPrinciples�� increase eye contact; increase eye contact;

decrease nondecrease non--communicative language; communicative language; emphasis on pragmatics; emphasis on pragmatics; use any effective modalityuse any effective modality

�� PECS PECS �� Picture Exchange Picture Exchange

Communication SystemCommunication System

�� Sign LanguageSign Language

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Sample Daily ScheduleSample Daily Schedule

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Occupational TherapyOccupational Therapy

�� Enhance upper Enhance upper extremity skills and extremity skills and visual motorvisual motor

�� Sensory Integration Sensory Integration treatment treatment controversial? controversial? �� Addresses sensory Addresses sensory

abnormalitiesabnormalities

�� Positive effects described Positive effects described as as ““systematic systematic desensitizationdesensitization””

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Sensory Integration TherapySensory Integration Therapy

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Medical EvaluationMedical Evaluation

�� Dysmorphology exam: woods lampDysmorphology exam: woods lamp

�� Metabolic StudiesMetabolic Studies --hypotonia, hypoglycemia hypotonia, hypoglycemia �� Serum amino acid and/or urine organic acid [<5% Serum amino acid and/or urine organic acid [<5%

with metabolic disorder]with metabolic disorder]�� Thyroid function Tests, Lead levelThyroid function Tests, Lead level

�� Electrophysiology: EEG, MEGElectrophysiology: EEG, MEG�� Starring spellsStarring spells

�� Neuroimaging: MRI , PETNeuroimaging: MRI , PET

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PsychopharmacologyPsychopharmacology

�� Adjunct to educational, developmental & Adjunct to educational, developmental & behavioral interventionsbehavioral interventions

�� Treat target symptomsTreat target symptoms�� sleep sleep ––insomnia, tantrums, irritability, insomnia, tantrums, irritability,

hyperactivity, attention span , selfhyperactivity, attention span , self--injurious injurious behavior, aggressionbehavior, aggression

�� Enhance ability to benefit from behavioral Enhance ability to benefit from behavioral interventions and optimize functioninginterventions and optimize functioning

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PsychopharmacologyPsychopharmacology

�� StimulantsStimulants�� Inattention, hyperactivityInattention, hyperactivity

�� Adderall, Ritalin, FocalinAdderall, Ritalin, FocalinConcertaConcerta

�� Mood stabilizersMood stabilizers�� Agitation, aggression, Agitation, aggression,

acting outacting out�� Trileptal, Depakote. Trileptal, Depakote.

TopamaxTopamax

�� Blood pressure medsBlood pressure meds�� Agitation, impulsivity, Agitation, impulsivity,

anxietyanxiety�� Tenex, ClonidineTenex, Clonidine�� IntunivIntuniv

�� Atypical NeurolepticsAtypical Neuroleptics�� stereotypies, stereotypies,

hyperactivity, aggressionhyperactivity, aggression�� Risperidol, Abilify, Risperidol, Abilify,

SeroquelSeroquel

�� SSRI SSRI (Selective Serotonin (Selective Serotonin ReRe--uptake Inhibitors)uptake Inhibitors)

�� obsessions, obsessions, perseveration, anxietyperseveration, anxiety�� Prozac, Zoloft. LuvoxProzac, Zoloft. Luvox

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ADHD symptomsADHD symptoms

�� InattentionInattention

�� ImpulsivityImpulsivity

�� HyperactivityHyperactivity

�� NoncomplianceNoncompliance

�� Impulsive aggressionImpulsive aggression

�� Difficult Social interactionsDifficult Social interactions

�� Deficits in Academic productivity and Deficits in Academic productivity and accuracyaccuracy

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Norepinephrine and ArousalNorepinephrine and Arousal

�� Brennan and Arnsten describe the effects of Brennan and Arnsten describe the effects of catecholamines on the prefrontal cortex with the catecholamines on the prefrontal cortex with the inverted U model. Too little or too much NE impairs inverted U model. Too little or too much NE impairs prefrontal cortex (PFC) cognitive abilities. prefrontal cortex (PFC) cognitive abilities.

�� NE is also involved in the processing of sensory NE is also involved in the processing of sensory stimuli and can increase the stimuli and can increase the ““ signal/noisesignal/noise ”” ratio of ratio of this stimuli (Brennan and Arnsten, 2008)this stimuli (Brennan and Arnsten, 2008)

�� This model provides a framework for deeper This model provides a framework for deeper understanding the cognitive deficits and understanding the cognitive deficits and ““ hypohypo ”” and and ““ hyperhyper ”” arousal symptoms in children with ASD.arousal symptoms in children with ASD.

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Locus CoerulusLocus Coerulus--Norepinephrine SystemNorepinephrine SystemDr. Rita ValentinoDr. Rita Valentino

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Arousal Dysregulation in ASDArousal Dysregulation in ASD

�� Arousal theories remain at the heart of clinician dialogue. Arousal theories remain at the heart of clinician dia logue. Children with ASD have been described by clinicians a nd Children with ASD have been described by clinicians a nd therapists as being either therapists as being either ““ hypohypo ”” or or ““ hyperhyper ”” aroused to internal aroused to internal and external stimuli. and external stimuli.

�� Hutt and colleagues in 1964 were the first to hypothesize that Hutt and colleagues in 1964 were the first to hypothe size that autism involved chronically high arousal levels. autism involved chronically high arousal levels.

�� Dawson and Dewey (1989) described a general overDawson and Dewey (1989) described a general over --arousal and arousal and narrow range of optimal arousal in autism.These hypo theses narrow range of optimal arousal in autism.These hypot heses have not been adequately investigatedhave not been adequately investigated

�� Neurocognitive theories do not explain the third core set of Neurocognitive theories do not explain the third core set of symptoms: symptoms: �� Behavioral rigidityBehavioral rigidity�� Over or under responsivenessOver or under responsiveness�� Unusual reactions to sensory stimuli Unusual reactions to sensory stimuli

�� (Rogers & Ozonoff, 2005). (Rogers & Ozonoff, 2005).

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Norepinephrine and ArousalNorepinephrine and Arousal

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Cognitive

function

Inverted-U Model

LOW HIGH

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Autism Spectrum DisordersAutism Spectrum DisordersBehavioral SymptomsBehavioral Symptoms

WithdrawnWithdrawn ADHD ADHD

UnresponsiveUnresponsive Anxiety & PanicAnxiety & Panic

SensorySeeking Sensory avoidingSensorySeeking Sensory avoiding

Depressed?Depressed? Mania ?Mania ?

LOW HIGH

Adequate

Sleep InsomniaPENN

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Alpha AgonistsAlpha Agonists

�� Tenex (Guanfaciene) 0.25mgTenex (Guanfaciene) 0.25mg-- 1mg 21mg 2--3 x a day3 x a day

�� Clonidine 0.025mg Clonidine 0.025mg ¼¼ TabletTablet-- 0.1mg every 40.1mg every 4--5 hrs5 hrs

�� Intuniv 1mg Intuniv 1mg --4mg XR guanfeciene4mg XR guanfeciene�� AdvantagesAdvantages

�� May be useful to treat very hyperactive or aggressiv e patientMay be useful to treat very hyperactive or aggressive patient�� May improve ability to fall asleepMay improve ability to fall asleep�� May reduce ticsMay reduce tics

�� DisadvantagesDisadvantages�� Less effective for inattentive symptomsLess effective for inattentive symptoms�� SedationSedation�� Risk of adverse CV effects and depressionRisk of adverse CV effects and depression�� Baseline EKGBaseline EKG

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StimulantsStimulants

�� Immediate release MPH (3Immediate release MPH (3 --4 hr)4 hr)

�� Ritalin Ritalin ®®, generic methylphenidate, generic methylphenidate

�� DexDex--MPH (3MPH (3--6 hr)6 hr)�� Focalin Focalin ®®

�� IntermediateIntermediate--acting MPH (6acting MPH (6--9 hr)9 hr)�� MetadateMetadate®® CD CD -- (30/ 70)(30/ 70)�� RitalinRitalin®® LA (50/ 50)LA (50/ 50)

�� LongLong--acting MPH (up to 12 hr)acting MPH (up to 12 hr)�� ConcertaConcerta®®

�� Focalin XRFocalin XR®®

�� DaytranaDaytrana®®

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AmphetaminesAmphetamines

�� ShortShort--acting AMP acting AMP -- 44--6 hour6 hour�� DexedrineDexedrine®®,, DextroStatDextroStat®®, generic dextro, generic dextro--amphetamineamphetamine

�� IntermediateIntermediate--acting AMP acting AMP -- 66--8 hour8 hour�� AdderallAdderall®® , Dexedrine , Dexedrine ®® spansules, generic mixed salts spansules, generic mixed salts

of amphetamine, Vyvanse of amphetamine, Vyvanse ®®

�� LongLong--acting AMP acting AMP -- 1010--12 hour12 hour�� Adderall XR Adderall XR ®®

�� VyvanseVyvanse

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American Heart Association ReportAmerican Heart Association ReportStimulants and Cardiac Risk: Stimulants and Cardiac Risk:

�� Careful history emphasizing personal and Careful history emphasizing personal and family history of heart diseasefamily history of heart disease

�� Careful physical examinationCareful physical examination

�� Baseline EKG (current EKG for those Baseline EKG (current EKG for those already on stimulants)already on stimulants)

�� Importance of sudden cardiac death registryImportance of sudden cardiac death registry

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Anxiety/OCDAnxiety/OCD

�� Repetitive behaviors or thoughtsRepetitive behaviors or thoughts

�� OCD behaviorsOCD behaviors

�� Difficulty with transitionsDifficulty with transitions

�� Extreme need for routineExtreme need for routine

�� Anxiety / Hyper arousalAnxiety / Hyper arousal

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Selective Serotonin Reuptake Selective Serotonin Reuptake InhibitorsInhibitors

�� Prozac 1mgProzac 1mg-- 40mg40mg

�� Zoloft 5mgZoloft 5mg-- 200mg200mg

�� Luvox 12.5mgLuvox 12.5mg-- 250mg250mg

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FDA approvedFDA approved Receptor sitesReceptor sites

�� 5HT 2 A and T75HT 2 A and T7

�� Alpha agonists 1 and 2Alpha agonists 1 and 2

�� Dopamine 2Dopamine 2

�� Histamine Histamine

�� 0.1 mg 0.1 mg up to up to 44--6 mg6 mg

RisperidoneRisperidone

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AntiAnti--Convulsants /Mood Convulsants /Mood stabilizersstabilizers

�� Moody, fast mood swingsMoody, fast mood swings

�� Crying, laughing (no reason) Crying, laughing (no reason)

�� Easily frustrated without antecedentEasily frustrated without antecedent

�� Abrupt violent aggressionAbrupt violent aggression

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AntiAnti--Convulsants /Mood Convulsants /Mood stabilizersstabilizers

�� Depakote (valproic acid)Depakote (valproic acid)

�� TegretolTegretol-- 22ndnd generation Trileptalgeneration Trileptal

�� TopamaxTopamax

�� LamictalLamictal

�� Benzodiazapene Benzodiazapene -- ativanativan

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Predominant Sleep Disorders in Predominant Sleep Disorders in ASDASD

Behavioral InsomniaBehavioral Insomnia -- SleepSleep -- Onset typeOnset type�� Limit settingLimit setting�� Sleep associationSleep association

Insomnia due to Pervasive Developmental Insomnia due to Pervasive Developmental DisorderDisorder�� Abnormal Melatonin Abnormal Melatonin �� High Arousal?High Arousal?�� Anxiety ?Anxiety ?

Wiggs & Stores 2004, Malow, 2006,2008, Souders, 2009 Wiggs & Stores 2004, Malow, 2006,2008, Souders, 2009 PENN

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HyperHyper --Arousal in InsomniaArousal in Insomnia

�� Current thinking on insomnia in Sleep Medicine regards the Current thinking on insomnia in Sleep Medicine regard s the disorder as one of hyperdisorder as one of hyper --arousal. arousal.

�� Early work : Internalization of emotional arousal Early work : Internalization of emotional arousal (M(Monroe, 1967) onroe, 1967)

�� Cognitive arousal theory hypothesis:Cognitive arousal theory hypothesis:�� increased cognitive activity: thinking and increased cognitive activity: thinking and

worrying while trying to fall asleep prevents worrying while trying to fall asleep prevents the initiation of the sleep processthe initiation of the sleep process

(Borkovec, 1982 Harv(Borkovec, 1982 Harv ey, 2002)ey, 2002)

�� Cognitive Behavioral therapyCognitive Behavioral therapy --InsomniaInsomnia

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MelatoninMelatonin

�� A powerful antioxidant molecule, involved in the regulation of A powerful antioxidant molecule, involved in the regulation of circadian and seasonal rhythmscircadian and seasonal rhythms

Brezinski,1997, N Engl J Med Brezinski,1997, N Engl J Med

�� Modulates neuronal plasticity, regulates circadian gene Modulates neuronal plasticity, regulates circadian gene expression and immune function expression and immune function

El Sherif, et al 2003El Sherif, et al 2003

�� Key role in communication behavior, song learning in birds Key role in communication behavior, song learning in birds Jansen et al 2005Jansen et al 2005

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MelatoninMelatonin

�� A powerful antioxidant molecule, involved in the regulation of A powerful antioxidant molecule, involved in the regulation of circadian and seasonal rhythmscircadian and seasonal rhythms

Brezinski,1997, N Engl J Med Brezinski,1997, N Engl J Med

�� Modulates neuronal plasticity, regulates circadian gene Modulates neuronal plasticity, regulates circadian gene expression and immune function expression and immune function

El Sherif, et al 2003El Sherif, et al 2003

�� Key role in communication behavior, song learning in birds Key role in communication behavior, song learning in birds Jansen et al 2005Jansen et al 2005

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Dr. Terri WeaverDr. Terri Weaver

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Melatonin: Potential side effectsMelatonin: Potential side effects�� Daytime SleepinessDaytime Sleepiness

�� Increased seizures? Increased seizures? Wasdell, 2008Wasdell, 2008

�� Effect on the CNS and direct Hypothalmus and pituitary gland actEffect on the CNS and direct Hypothalmus and pituitary gland action ion Pang et al 1998Pang et al 1998

�� NatureNature’’s contraceptive, photo periodic control in animal reproduction,s contraceptive, photo periodic control in animal reproduction,survival of the species survival of the species Pang, et al 1998Pang, et al 1998

�� Alterations in LH and FSH with melatonin level in the rat and ewAlterations in LH and FSH with melatonin level in the rat and ewe e Bittman, et al 1984, Kamberi, 1970)Bittman, et al 1984, Kamberi, 1970)

�� Gonads: target site of melatonin action in ducks and chickens Gonads: target site of melatonin action in ducks and chickens Ayre & Ayre &

Pang, 1994Pang, 1994

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Melatonin as a Treatment for InsomniaMelatonin as a Treatment for Insomnia

�� Systematic investigation into the role melatonin plays in ASD Systematic investigation into the role melatonin plays in ASD and the efficacy of exogenous melatonin as a hypnotic. Can also and the efficacy of exogenous melatonin as a hypnotic. Can also be used a chronobiotic but not studied this way.be used a chronobiotic but not studied this way.

��Wasdell et al 2008 n= 50 randomized control trial Wasdell et al 2008 n= 50 randomized control trial --crossover crossover designdesign

��Garstang et al 2006 n=7 randomized control trialGarstang et al 2006 n=7 randomized control trial--crossover crossover designdesign

��Anderson et al 2008 n=107 retrospective, chart reviewAnderson et al 2008 n=107 retrospective, chart review��Giannotti, et al 2006 n=25 open label prospectiveGiannotti, et al 2006 n=25 open label prospective

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RecommendationsRecommendations

�� No practice guidelines at the Regional Autism No practice guidelines at the Regional Autism CenterCenter

�� Benefit/risk ratio on a case by case basisBenefit/risk ratio on a case by case basis�� Sleep hygiene and behavioral interventions should be Sleep hygiene and behavioral interventions should be

tried firsttried first�� Melatonin start slow, increase dose by 0.3mg ?Melatonin start slow, increase dose by 0.3mg ?�� UMMC web site recommends starting at 0.3mg, liquid UMMC web site recommends starting at 0.3mg, liquid

preparation and increasing slowlypreparation and increasing slowly�� Synthetic melatonin, pharmaceutical gradeSynthetic melatonin, pharmaceutical grade��Avoid possible animal contaminationAvoid possible animal contamination��Reputable company, with quality control systemsReputable company, with quality control systems

��

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Complementary and Alternative Complementary and Alternative TreatmentsTreatments

�� Vitamin A, CVitamin A, C

�� B6 and MagnesiumB6 and Magnesium

�� DMG DMG [Dimethylglycine][Dimethylglycine]

�� Diet: Casein/ gluten Diet: Casein/ gluten free; other eliminationfree; other elimination

�� ImmunotherapyImmunotherapy

�� Yeast/ Antifungal Yeast/ Antifungal therapytherapy

�� SecretinSecretin

�� Antibiotics/ AntiviralsAntibiotics/ Antivirals

�� Hyper baric therapyHyper baric therapy

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Family SupportFamily Support

�� Early YearsEarly Years�� Seeking a Seeking a ““ DiagnosisDiagnosis ””

�� Finding therapistsFinding therapists�� Family balanceFamily balance

�� Financial CostFinancial Cost�� BondingBonding

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Family SupportFamily Support

�� School Age YearsSchool Age Years�� Physical demands/time demandsPhysical demands/time demands

�� EmploymentEmployment�� Social isolationSocial isolation

�� Role restrictionsRole restrictions�� Strain on marriageStrain on marriage

�� Respite careRespite care

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Family SupportFamily Support

�� Teen/Adult TransitionTeen/Adult Transition�� SexualitySexuality

�� SafetySafety�� Services Services ““ What do I do when the school What do I do when the school

bus doesnbus doesn ’’ t come anymore?t come anymore? ””�� Respite CareRespite Care

�� Residential placementResidential placement�� Job training/ Life skills coachingJob training/ Life skills coaching

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Thank youThank you