Michael Gramlich Child Psychopathology Fall 2014 Tourette Syndrome (TS)

Michael GramlichChild Psychopathology

Fall 2014

Tourette Syndrome (TS)

Outline

DSM-5 description of Tourette syndrome

Literature review

Conclusion: recommended revisions to the DSM-5

Tourette Syndrome: Diagnostic Criteria

Tourette Syndrome Criteria

A. Multiple motor and one or more vocal tics that have been present at some time during the illness, although not necessarily concurrently.

B. The tics may wax and wane in frequency but have persisted for more than 1 year since first tic onset.

C. Onset is before age 18 years.

D. The disturbance is not attributable to the physiological effects of a substance (e.g., cocaine) or another medical condition (e.g., Huntington’s disease, postviral encephalitis).

(American Psychiatric Association, 2013)

Tic Disorders

1. Tourette Syndrome (a.k.a. Tourette’s Disorder)

2. Persistent (Chronic) Motor or Vocal Tic Disorder Motor OR vocal tics

Specify: “motor tics only” or “vocal tics only”

3. Provisional Tic Disorder Motor AND/OR vocal tics

Tics < 1 year

4. Other Specified/ Unspecified Tic Disorder Specified: criteria for tic disorder not met. Ex: onset after age 18 years

Unspecified: chooses not to specify reason or insufficient information

DSM-5 Classification: “Neurodevelopmental Disorders” “Motor Disorders”


Clinical Manifestations

Simple motor tics / simple vocal tics

Short duration (i.e., milliseconds)

Eye blinking, shoulder shrugging; throat clearing, grunting

Complex motor tics / complex vocal tics

Longer duration (i.e., seconds)

Often present as a combination of simple tics

Touching, squatting, jumping

Words and phrases Echolalia / Palilalia HBO: Tourette Syndrome Clip

Coprolalia

Echopraxia

Copropraxia (American Psychiatric Association, 2013)

http://www.youtube.com/watch?v=HPmpIY7XJVE

Development and Course

Premonitory urge Sensation that precedes tics

Unpleasant itch, tingle, or tension

This urge is released following expression of the tic

Vulnerability toward certain co-occurring conditions changes with the course of tic disorders Prepubertal children: ADHD, OCD, and *Separation Anxiety

Disorder

Teenagers & Adults: MDD, Substance Use Disorder, or Bipolar Disorder


Risk and Prognostic Factors

Temperamental (Exacerbating/Alleviating) Factors Tics are worsened by anxiety, excitement, and exhaustion Tics are better during calm and focused activities

Environmental People may incorrectly interpret a tic (e.g., repeating the last-heard word or

phrase – echolalia) as purposeful Problem when interacting with authority figures (e.g., substitute teachers)

Genetic Important risk alleles for Tourette syndrome Rare genetic variants in families with tic disorders have been identified

Physiological Obstetrical complications (i.e., difficulties during labor or delivery) Older paternal age Lower birth weight Maternal smoking during pregnancy


Functional Consequences

Sometimes mild to moderate symptom severity involves no distress or impairment in functioning

The presence of co-occurring conditions (e.g., ADHD or OCD) can have a greater impact on functioning

Tic disorders can result in social isolation, interpersonal conflict, peer victimization, inability to work or go to school, and lower quality of life

Rare complications of Tourette syndrome can include: physical injury (e.g., from hitting oneself in the face) orthopedic and neurological injury (e.g., disc disease related to

forceful head and neck movements)


Differential Diagnosis


Disorder Description Primary Difference

Motor Stereotypies Involuntary, rhythmic, repetitive, movements

Prolonged Duration (seconds to minutes) Lack of a premonitory urge

Chorea Brief, purposeless, appears “dance-like”

Vocal tics are not characteristic Movements are usually worsen during attempted voluntary action

Dystonia Muscles contract involuntarily, severe twisting or distorted postures

Often triggered by attempts at voluntary movement s Not seen during sleep

Myoclonus Unidirectional movement, nonrhytmic, occur during sleep

Rapidity Lack of suppressibility Absence of premonitory urge

OCD Obsessions, and/or compulsions

Cognitive-based drive (e.g., fear of contamination) Perform actions a certain number of times, equally on both sides of the body

DSM-5 Model of Tourette Syndrome

Genetic & Physiological Factorso Risk alleleso Older paternal ageo Lower birth weighto Obstetrical complicationso Maternal smoking during

pregnancy

Environmental Factorso Perception by others

Exacerbating Factorso Anxietyo Excitemento Exhaustiono Stressful events

Core Featureso Motor Tics &o Vocal Tics

Secondary Featureso Premonitory Urgeso ADHD o OCD

Functional Consequenceso Social isolationo Interpersonal conflicto Peer victimizationo Inability to work/ go to schoolo Physical injury

Alleviating Factorso Focused activities

Prevalence/Onset of TS Clinical Features Heritability + Genetics Comorbidity Risk Factors Brain Structures Neurotransmitters Tic Suppression Exacerbating/Alleviating Factors Quality of Life Treatment

Literature

Prevalence and Onset of TS United States prevalence, ages 5 – 18 years: ~ 1% (range 0.5 – 3.8%)

(Comings D., Himes, Comings B., 1990; Kurlan et al., 2001; Robertson, 2008)

International prevalence, ages 5 – 18 years: ~ 1%(Robertson, 2008)

Mean age at onset of tics: ~ 4 years - 6.4 years(Freeman et al., 2000; McMahon, Carter, Fredine, & Pauls, 2003)

Motor tic onset ~ 4 – 6 years Vocal tic onset ~ 8 – 15 years Simple tics usually precede complex tics

(Leckman, Bloch, Scahill, & King, 2006)

Mean age at diagnosis of TS: 13.2 years (51.4% 6 -10 years)(Freeman et al., 2000)

Children – male to female 5:1 Adults – male to female 3:1

(Freeman et al., 2000)

Course of Tic Severity

(Leckman et al., 1998)

Temporal Nature of Tics

(Figure 1. Adapted from Leckman, 2002)

CoprophenomenaFreeman et al. (2009) N = 597 TS patients (children, n = 506; adults, n = 91)

Coprolalia: lifetime prevalence Males: 19.3% Females: 14.6% Mean onset: 5 years, 4 months after the onset of tics

Copropraxia: lifetime prevalence Males: 5.9% Females: 4.9% Mean onset: 4 years, 10 months after the onset of tics

Coprophenomena 18.4% of children and 28.6% of adults

Coprolalia: 6.8% mildly-rated tics and 42.6% rated severe tics

Heritability: First-degree Relatives

TS Controls

TS = 8.7% (± 1.6%) 0%

CTD = 17.3% (± 2.1%) 2.7% (± 2.7%)

OCD = 11.5% (± 1.9%) 2.5% (± 2.5%)

TS - OCD TS + OCD

TS = 9% (± 2.0%) 8.1% (± 2.6%)

CTD = 17.6% (± 2.7%) 17.6% (± 3.6%)

OCD = 10.4% (± 2.3%) 13.6% (± 3.6%)

Note: 10.4% OCD among TS only probands was significantly greater than 2.5% among Controls

TwinsTS Concordance Rate:

Monozygotic twins 53% vs. Dizygotic twins 8%(Price, Kidd, Cohen, Pauls, & Leckman, 1985)

Hyde, Aaronson, Randolph, Rickler, and Weinberger (1992) 16 MZ twins (M = 12.8 years, SD = 1.4, range = 8 – 26 years; 75% males) At least one twin with TS Concordance rate: 56% TS and 94% tic disorder 13 MZ pairs had different birth weights

12/13: lower birth-weight twin had a higher tic severities (both: YGTSS and Shapiro Symptom Check List)

GeneticsAlthough family and twin studies have demonstrated high relative risk, researchers have difficulty mapping the genes responsible.

Genome scan among affected sibling pairs (N = 1,052 participants) and multigenerational families (N =15 families). Overall, this study found strong linkage on chromosome 2p. However, this linkage was absent in some families. In addition, some families appear to have stronger associations on specific markers along chromosome 2 (e.g., DS2S319 or D2S305).

(The Tourette Syndrome Association International Consortium for Genetics, 2007)

Gene studies have found mixed support on candidates involved in neurotransmission. Dopamine receptor D2 (DRD2), receptor D4 (DRD4), Monoamine oxidase A (MAOA), and

Serotonin receptor (5-HT2A) However, results have not been clearly replicated.

(O’Rourke, Scharf, Yu, & Pauls, 2009)

GWAS of Tourette Syndrome 1,285 TS cases and 4,965 ancestry-matched controls of European descent No markers achieved a genome-wide threshold of significance (other neuropsychiatric

GWAS have needed at least 5,000 cases to identify common risk alleles; see Sullivan, 2010) Top signal marker rs7868992 on chromosome 9q32, gene COL27A1

(Scharf et al., 2013)

Comorbidity

TS alone: 10% ~ 20% among children and adults(Freeman et al., 2000; Khalifa and von Knorring 2006; Mol Debes, Hjalgrim, & Skov, 2008)

OCD: 16% ~ 50%(Khalifa et al., 2006; Mol Debes et al., 2008)

ADHD: 43% ~ 68%(Khalifa et al., 2006; Mol Debes et al., 2008)

Both OCD & ADHD: 21.7%(Mol Debes et al., 2008)

Depressive Disorder: 20% Anxiety Disorder: 18% Conduct Disorder: 8% ~ 15% Learning Disorder (i.e., dyslexia): 16% Intellectual Disability (IQ ≤ 70): 16% Sleep Disorder: 25% ~ 28% Stuttering: 8% ~ 15%

(Freeman et al., 2000; Khalifa et al., 2006; Mol Debes et al., 2008)

Comorbid ADHD: FunctioningCarter et al. (2000) TS + ADHD (n = 33; M = 11.10 years; SD = 1.56; males = 76%) TS alone (n = 16; M = 10.40 years; SD = 1.41; males = 56%) Controls (n = 23; M = 10.80 years; SD = 1.77; males = 48%)

No significant differences in OCD and OC symptoms between TS + ADHD and TS alone

Measures Kaufman Brief Intelligence Test CBCL Vineland Adaptive Behavior Scales – Survey Form Children’s Depression Inventory (CDI): child-rated Self-Perception Profile for Children Family Environment Scale (FES) Dyadic Adjustment Scale (DAS) 20-Item Leyton Survey YGTSS CY-BOCS Continuous Performance Test (CPT)

(Carter et al., 2000)

Results

Comorbid OCD

Tic-related OCD has a higher rate among males, an earlier age of onset, poorer treatment responses to SSRI medication, and higher heritability among first-degree relatives.

(Cohen, Leckman, & Bloch, 2013)

(Bloch et al., 2006a)

Comorbid Sleep DisordersGhosh et al. (2014) 123 TS children (13.6 years, SD = 3.8) Clinical interview with TS child and guardian

TS-only group: 31 of the 48 (65%) had DSM-V coded sleep disorder 10 of the 31 (32%) had primary insomnia disorder

Represents a 2.5–fold increase in comparison to the general pediatric population ~ 20% of the entire TS-only sample

0% had insomnia secondary to medication

TS + ADHD group: 48 of the 75 (64%) had DSM-V coded sleep disorder 20 of the 48 (42%) had primary insomnia disorder 16 of 48 (33%) had insomnia secondary to medication (e.g., extensive use of

stimulant medications)

Prenatal Risk Factors

Chao, Hu, and Pringsheim (2014) Systematic review on 21 studies Most data were ascertained retrospectively 5 studies collected data prospectively

Results No significant association for demographic factors of parents (i.e., age, education,

SES, and marital status) with onset of TS, symptom severity, or comorbidity. Most consistently reported factors were maternal smoking during pregnancy and

low birth weight. Maternal smoking was associated with TS onset and comorbid ADHD and OCD, and

symptom severity of ADHD and OCD. Low birth weight: comorbid ADHD and tic severity

Note: Although these factors are related to tics, they do not necessarily cause tics.

PANDAS TheoryPediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS)

Infection: Group A beta hemolytic streptococci (GABHS) Patients may develop tics in reaction to recurrent strep infections

Mell, Davis, and Owens (2005) Examined the rates of streptococcus infection among children (N = 144) prior to OCD,

Tourette’s Syndrome (TS), or tic disorder diagnosis. Children with OCD, TS, or tic disorder were more likely than controls to have a streptococcus infection 3 months before date onset. The highest risk was multiple streptococcus infections within 12 months of diagnosis (OR: 3.10; 95% CI: 1.77, 8.96).

Published reports linking GABHS with pediatric neuropsychiatric symptoms: onset of OCD/tics symptoms, hyperactivity, and even disrupted handwriting (Murphy, Kurlan, &

Leckman, 2010). However, these studies are mostly retrospective.

PANDAS Pathogenesis Model: Frequent GABHS infections anti-GABHS antibodies crossing blood-brain barrier dopamine release inflammation within basal ganglia OCD, tics and other neuropsychiatric symptoms (Murphy et al., 2010)

Cluster Analysis of Tic Symptoms and Tx OutcomeMcGuire et al. (2013) 142 youths (M = 12.45 years; SD = 2.83); 97 Adults (M = 35.17 years; SD = 13.09) TS (n = 212), Chronic Tic Disorder – motor (n = 25) – vocal (n = 2) Woods et al., 2008; Piacentini et al., 2010; Wilhelm et al., 2012

Cognitive Behavioral Intervention for Tics (CBIT)

Yale Global Tic Severity Scale (YGTSS): clinician-rated instrument Checklist of 40 possible tic symptoms Tics during the past week:

1. Number (0-5)

2. Frequency (0-5)

3. Intensity (0-5)

4. Complexity (0-5)

5. Interference (0-5) Total Motor Tic (0-25) severity Total Phonic Tic (0-25) severity Total Tic score (0-50) severity YGTSS Impairment scale (0-50)

Clinical correlates No significant differences in cluster membership across various TS/OCD/ADHD profiles [Cluster 1: F (3, 235) = 1.36, p = 0.26; Cluster 2: F (3, 235) = 2.06, p = 0.11; Cluster 3: F (3, 235) = 0.70, p = 0.55; Cluster 4: F (3, 235) = 1.54, p = 0.21].

Treatment Responses Cluster membership did not predict treatment response [Cluster 1: OR = 0.95, 95 % CI = 0.64 – 1.41; Cluster 2: OR = 1.18, 95% CI = 0.81 – 1.72; Cluster 3: OR = 0.97, 95% CI = 0.65 – 1.46; Cluster 4: OR = 1.26, 95% CI = 0.85 – 1.86]

Cluster membership did not predict reductions in total tic severity [F (4, 115) = 0.47, p = 0.77, R2 = .02] or individual motor tic severity [F (4, 115) = 0.47, p = .77, R2 = .02] or phonic tic severity [F (4, 115) = 1.64, p = .17, R2 = .05].

TS Characteristics: mean age of onset between 4 – 6 years, tic severity peaks ~ 10 years, and the frequency is sporadic. Motor tic onset typically precedes vocal tics and simple tics commonly start before complex tics. Males have a higher rate of prevalence. Coprophenomena only occurs in about 1 in 5 TS patients

Heritability: having a first-degree relative with TS significantly increases the risk of having TS, CTD, and/or OCD. In addition, rates of TS and tic disorder were significantly higher for monozygotic twins (~ 50% and 94%) in comparison to dizygotic twins.

Genetics: genetic linkage studies, candidate genes, and GWAS have suggested some genes that are responsible. However, these findings are limited and need replication.

Perinatal Risk Factors and PANDAS: the most consistent findings point to low birth weight and maternal smoking during pregnancy as correlates with TS and tic severity. However, these do not imply causation, only association. Furthermore, PANDAS has shown evidence, but this is only among a small group of tic disorder patients.

Comorbidity: ~ 10% - 20% have TS alone. High rates of co-occurring ADHD, OCD, and sleep disorders. Furthermore, comorbid ADHD significantly increases problems with behavior.

Four-cluster tic symptoms: no differences among TS/ADHD/OCD profiles. Cluster membership did not predict treatment response to CBIT and did not predict reduction in tic severity (total, motor, or vocal).

Review


Literature

Fine-motor SkillsBloch, Sukhodolsky, Leckman, and Schultz (2006b) 32 TS children (M = 11.4 years, SD = 1.5) and 9 age-matched controls Follow-up clinical assessment at an average of 7.4 years later

Time 1 OCD and Tic severity Neuropsychological Tests:

Kaufman Brief Intelligence Test: short form intelligence Beery-Buktenica Visual Motor Integration Test (VMI): visual motor integration Rey-Osterreith Complex Figure Task (RCFT): visual memory Purdue Pegboard: fine motor skill

Time 2 OCD and Tic severity

Results: Purdue Pegboard ‘Dominant’ (p = .012, R2 = .19), ‘non-dominant’ (p = .003, R2 = .26), and ‘bimanual’ (p

= .045, R2 = .13) were positively correlated with current tic severity at Time 1. Poor performances on the ‘dominant’ predicted worse tic severity at Time 2 (OR = .59,

p = .04, R2 = .13).

Peterson et al. (2003)

Functional magnetic resonance imaging (fMRI) examining 154 TS and 130 control participants (18.7 years ± 13.4 vs. 21.0 years ± 13.5; p = .14) 173 (60.9%) were children 111 (39.1%) were adults 33.1% had TS + OCD 26.6% had TS + ADHD

Structural Imaging: Basal Ganglia

Suppression of movement

signals

“Breaking system” of the

brain

TS vs. Controls Significantly smaller basal ganglia volumes for TS participants than controls (p = .04)

TS x Region (p < .001) Relatively greater reductions in the caudate (p = .009) than in the putamen (p = .16),

and globus pallidus (p = .31) relative to controls

Children Only Smaller volumes in the caudate (p = .06) than in the globus pallidus (p = .09), and the putamen (p = .30) in comparison to controls

Adults Only Smaller volumes in the caudate (p = .04), globus pallidus (p = .13), and the putamen (p = .11) in comparison to controls

Results

(Peterson et al., 2003)

Structural Imaging: Basal GangliaBloch, Leckman, Zhu, and Peterson (2005)

Prospective, longitudinal study assessing 43 TS patients at baseline and follow-up

Baseline Average age = 11.4 years, range = 8.5 – 13.9, SD = 1.6 Yale Global Tic Severity Scale (YGTSS) Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) [35% OCD] Kaufman Brief Intelligence Test fMRI

Follow-up Average age = 18.7 years, range = 16-23 years, SD = 1.7 YGTSS CY-BOCS Global Assessment Scale

TIME 1: Tic and OCD Severity at time of Childhood MRI No association between caudate volume and Tic severity (p = .08) or OCD severity (p

= 0.59)

TIME 2: Tic and OCD Severity at time of Early Adulthood follow-up Volumes of caudate correlated inversely with Tic severity

Total Caudate (χ2 = 11.3, p = .0008) Left Caudate (χ2 = 13.2, p = .0003) Right Caudate (χ2 = 8.8, p = .003)

Volumes of caudate correlated inversely with OCD severity Total Caudate (χ2 = 6.9, p = .009) Left Caudate (χ2 = 7.2, p = .007) Right Caudate (χ2 = 6.3, p = .012)

The putamen and the globus pallidus were not correlated with Tic or OCD severity

Results

(Bloch et al., 2005)

Functional Imaging: Tic Suppression

Peterson et al. (1998) 22 TS adults without significant head tics and who could voluntarily suppress their

tics. 11 men and 11 women (these groups did not differ significantly in tic severity). Compared functional images during tic suppression and free expression of tics.

40-second sessions of “suppression” and “free expression” of tics within the scanner.

BOLD Signal Changes “Free” “Suppression” Events and Severity of Motor Tics Right Caudate Nucleus (r = - .46, p < .02) Putamen

Right (r = - .54, p < .009) Globus Pallidus

Left (r = - .47, p < .03) Right (r = - .52, p < .03)

Thalamus Left (r = - .44, p < .02) Right (r = - .41, p < .02)

Left Sensorimotor Cortex (r = - .36, p < .05) Left Inferior Parietal (r = - .43, p < .02)

Key Finding: TS participants whose signal change exhibited reduced activation between events, had more severe symptoms.

Results

(Peterson et al., 1998)

Structural Imaging: Sensorimotor CorticesSowell et al. (2008)

The average cortex in the TS group was 0.45 mm thinner thanthe controls.

Age-by-diagnosis interaction where cortices thickened with increasing agein control children, but not in those with TS.

Supplemental Motor Area (SMA)

Hampson, Tokoglu, King, Constable, & Leckman (2009)

Neurotransmitters

GABAergic neurons and Cholinergic neurons (a.k.a., acetylcholine) Individuals with TS showed a reduction in up to 60% of the GABAergic and

cholinergic interneurons in the caudate nucleus and putamen. In addition, the GABAergic neurons were markedly decreased in the external

segment of the globus pallidus (GPe), while significantly increased in the globus pallidus interna (GPi).

(Kalanithi et al., 2005; Kataoka et al., 2010)

Dopaminergic Systems Dopamine (D2) receptor antagonist pharmaceuticals such as haloperidol have

been found to be successful at suppressing tics temporarily.(Scahill et al., 2006)

Tetrabenazine (TBZ) acts as an inhibitor of dopamine (D2) and other monoamines (norepinephrine and serotonin) and has demonstrated tic suppression. Also has showed little to no reports of TBZ-induced tardive dyskinesia.

(Kenney, Hunter, & Jankovic, 2007)

Increases in tics following exposure to increased dopaminergic activity in the central nervous system (CNS) such as L-dopa

(Anderson, Leckman, & Cohen, 1998. As cited in Leckman, Bloch, Smith, Larabi, & Hampso, 2010)

Neurotransmitters

Noradrenergic System Alpha-2 adrenergic agonists such as clonidine, have reported to reduce tic severity

Clonidine’s primary action is inhibition of norepinephrine (results in reduced dopamine in the striatum). Fewer side effects and long term risk potential in comparison to traditional dopamine antagonists

(Bloch, Panza, Landeros-Weisenberger, & Leckman, 2009)

Adult TS patients have showed elevated levels of cerebrospinal fluid (CSF) norepinephrine and higher levels of norepinephrine in their urine in response to lumbar puncture stress relative to healthy controls

(Chappell et al., 1994; Leckman et al., 1995; As cited in Leckman et al., 2010)

Serotonergic System Although serotonin reuptake inhibitors (SRIs) are effective in treating OCD, SRIs are

less effective in treating tics and tic-related OCD. (March et al., 2007; Scahill et al., 2006)

Inconsistencies in the literature regarding abnormalities of serotonin between TS alone subjects and healthy controls

(Leckman et al., 2010)


Literature

Tic Suppression: Verbal Instructions and Reinforcement

BL: BaselineVI: Verbal InstructionDRO: Reinforced Suppression

Woods and Himle (2004) N = 4 (3 boys, 1 girl) Token dispenser (“Tic detector”) Remote controlled operant tokendispenser.

BL condition: Tic freely

VI condition: Verbal instructions not to tic

DRO condition: Verbal instructions not to tic Told every10-secs of tic-free intervals,

token would be awarded.

Results Adding reinforcement toverbal instructions reduced tics by 76% Consequences can affect tic

expression

“Tic Detector”

Premonitory Urges…Negative Reinforcement?

Premonitory Urge(unpleasant)

Expression of TIC

Termination of URGE

Situational Antecedents

Figure by Piacentini J., “New Thoughts on Behavioral Treatment of Tourette Syndrome.”

February, 2006

Himle et al. (2007) 5 TS children (ages 8, 10, 13, 14, and 17) Inclusion: presence of premonitory urges, tic rate at least 1/min, and no previous

behavioral treatment for tic suppression

Measures Anxiety Disorders Interview Schedule-4th Edition (ADIS-IV) Child Behavior Checklist (CBCL) Yale Global Tic Severity Scale (YGTSS) Premonitory Urge for Tics Scale (PUTS) Direct-observation

Materials “Tic Detector” (established by Woods et al., 2004). Laptop computer displayed a 9-point “urge thermometer” every 30s

Design (ABAB withdrawal) – 5-minute conditions Baseline: “feel free to tic” Suppression: earn a token for each 10s tic-free intervals. Interval resets if tic occurs.

Tic Suppression and Premonitory Urge

Results

4/5 children displayed a clear and reliable suppression effect 3/4 children reported more intense premonitory urges during suppression(DRO) in comparison to BL conditions. The older children (e.g., Randy) had a greater ability to suppress the tics.

(Himle et al., 2007)

17 Year Old Male14 Year Old Male10 Year Old Female

Development of Premonitory UrgeWoods et al. (2005) Premonitory Urge for Tics Scale (PUTS): 9-item self-report 42 TS children (8 to 16 years old) Young: 8 – 10 years old vs. Old: 11 – 16 years old

PUTS Scores: Young vs. Old Total PUTS scores (M = 18.5 ± 6.5 vs. M = 18.6 ± 7.3, p = ns) Frequency of urges (items 7 and 8, p = ns)

PUTS Consistency Internal consistency: Young vs. Old (α = 0.57 vs. α = 0.89)

CONCLUSION: Researchers suggested the sensations are present and temporally stable in Young and Old youths, but Old youths can reliable notice and describe it.


Literature

Happen immediately before tics and make them more or less likely to occur

Internal (e.g., premonitory urges, anxiety, or boredom)

External (e.g., sports, the presence of other people, or being home from school)

Antecedents

Events after tics that make the frequency or intensity of tics more or less likely to happen

Internal (e.g., embarrassment, or relief from premonitory urge)

External (e.g., attention from family or peers, escape from activities)

ConsequencesTics

Contextual Factors

Conelea and Woods (2008a)

(Table 6 adapted from Cohen et al., 2013)

Reinforcement and Context

Woods, Walther, Bauer, Kemp, and Conelea (2009) 10 children with TS (n = 9) or Chronic Tic Disorder (n = 1) Mean age of 10.8 years (9-15 years old)

4 Training sessions, consisting of 3 conditions

1. Purple light (verbal instructions to suppress, reinforced suppression)

2. Orange light (verbal instructions to suppress, no reinforced suppression)

3. No light (baseline, verbal instructions to tic freely) Each 5-min condition replicated 3 times in random order during each training session

5th session was a test of acquisition Verbal instructions to suppress (or not suppress) were not provided Purple light, orange, no light condition presented 3 times No reinforcers delivered

* (Reinforcement via “Tic Detector” protocol utilized by Woods et al., 2004).

TRAINING PHASE Mean Tics Per Minute (TPM):

BL > SUP-Purple (p = .002, d = 1.10) 63.6% reduction in TPM was found during the training phase for SUP-Purple

Mean Tics Per Minute (TPM): Training Phase SUP-No Reinforcement-Orange > SUP-Purple (p = .03, d = 0.47)

TEST – 5th Session TPM: BL-Test condition > Test-Purple (p = .003, d = 0.66)

Key Finding: Situation where previous reinforcement took place can be learned and applied to later tic expressions

Results

Impact of Attention on TicsConelea and Woods (2008b) 9 TS children (M = 11.5 years, range = 9 – 15) ADHD 4/9 (ADIS-IV ratings; 6, 4, 4, 4)

Followed protocol performed by Woods et al., 2004 (e.g., token dispenser and one-way mirror observation).

Continuous Performance Test Audio presentation of letters (200 single-letter trials) ‘A-L’ sequence was the target among 10 non-target letters Completed CPT at pre- and post-experiment and SUP + DIS conditions

Conditions1. Baseline (BL): tic freely, told tic detector was on but would not dispense tokens

2. Suppression (SUP): reinforced via tokens

3. Suppression and Distraction (SUP + DIS): reinforced via tokens + complete auditory CPT

Suppression findings Tic frequencies BL > SUP (p = .02, d = 1.34) and SUP + DIS (p = .03, d = 1.29) Tic frequencies between SUP (a.k.a. DRO) and SUP + DIS did not differ

CPT accuracy findings Pre and post scores did not differ so they were combined Hits: SUP + DIS < Pre/Post (p = .04, d = .77) Errors: did not differ between Pre/Post and SUP + DIS

Results

(Conelea et al., 2008)

Impact of Stress on Tic FrequenciesConelea, Woods, and Brandt (2011) 8 TS and 2 Persistent (Chronic) Tic Disorder (ages 9-17 years)

Followed protocol performed by Himle et al., 2007 (e.g., token dispenser, “urge thermometer”)

STRESS Task Timed mental math task 4 sets that increased in difficulty (e.g., “9 – 3 – 2” to “7y – 10 = 18”).

Conditions1. Baseline (BL)

2. Reinforced Suppression (SUP)

3. Reinforced Suppression plus Stress Induction (SUP + STRESS)

4. Stress Induction (Stress)

- Each condition was 5 minutes, each condition was performed twice

Results

(Conelea et al., 2011)

Mean Tics Per Minute SUP < BL (p = .01, r = -.69) BL = STRESS (p = .79) SUP + STRESS > SUP (p = .01, r = -.69)

Stress Rating STRESS > BL (p = .03, r = .57) SUP < SUP + STRESS (p = .03, r = .57)

Urge Rating (Try to ignore data – collected every 5-mins previous study Himle et al., 2007 was 30-secs)

Key finding: stress might disrupt suppression, not increase tics overall


Literature

Peer RelationshipsStokes, Bawden, Camfield, Backman, & Dooley (1991) Evaluated 29 TS youngsters (M = 11.4 years) TS participants completed self-esteem scales and neuropsychological testing Teachers and parents completed behavior rating scales (i.e., CBCL) Classmates completed the Pupil Evaluation Inventory (PEI)

Provides measures of aggression, withdrawal, and likeability Classmates served as the control group

Peer Relationships Rated as more withdrawn (p < .02) by their classmates Rated as less popular (p < .005) by their classmates 35% of TS sample received the lowest rating in the class on 1 or more PEI factors Teachers rated TS children as more aggressive (p < .025) and more withdrawn (p

< .005) Comorbid ADHD diagnosis were rated as more aggressive by their classmates

than TS children without ADHD (p < .02)

Note: these social problems were not predicted by the frequency or duration of tics.

Social Functioning

Champion, Fulton, and Shady (1988) 210 TS participants (ages 3-60+; 70% were school-aged children) Survey examining type and frequency of tics, degree and nature of sleep disorders,

the degree and nature of associated behavior problems, the TS individual’s perceived level of psychosocial functioning, and perceived level of support from others.

42% of respondents reported problems in forming and maintaining friendships.

~ 50% reported problems with dating as a result to having TS.

Family members, including spouses when applicable, and physicians were rated as most supportive.

Teachers who were educated about TS were found to be more supportive than teachers who lacked knowledge about TS.


Literature

Habit Reversal Training (HRT)Arzin and Nunn (1973) Introduced “Habit-Reversal” treatment Treated 12 individuals with habits or tics 90% symptom reduction after 1 session 99% symptom reduction at 3 month follow-up

1. Awareness Training Detect pre-tic warning signs (e.g., premonitory urges)

2. Competing Response Training Blocks tics and sustainable Ex: crossing arms so that a certain motor tic cannot take place or breathing a

certain way that is incompatible with a vocal tic Perform CRT for 1-3 minutes following temptation to perform tic

3. Motivational and/or Ancillary Techniques – includes social support and behavioral reward system Ex: praise from family, friends, or teachers for successful effort

Comprehensive Behavioral Intervention for Tics (CBIT)

1. Psychoeducation

2. Habit Reversal Training

3. Functional Intervention

4. Reward System

5. Relaxation Training

CBIT StudyPiacentini et al. (2010) 126 TS or CTD children (age range: 9 -17 years) studied at 3 sites (UCLA, Johns

Hopkins University, and U. of Wisconsin – Milwaukee)

Study Treatments

1. CBIT

2. Psychoeducation/Supportive Therapy – Therapists were prohibited from providing direct instructions about tic management.

At 10 weeks evaluation + positive responders continued treatment to 3 months At 3 months evaluation + treatment sessions discontinued At 6 months follow-up evaluation

Primary Outcome Measures YGTSS - Total Tic Score [0-50] YGTSS - Impairment [0-50] Clinical Global Impressions (CGI) - Improvement Scale [1-8]: determined by clinician

10 Weeks YGTSS Total Tic Score CBIT > PST reduction in tics (p < .001, d = .68)

10 Weeks CGI Improvement (Very Much Improved “1” or Much Improved “2”) CBIT > PST positive treatment response (52.5% vs. 18.5%, p < .001)

CBIT = 32/61 participants PST = 12/65 participants

10 Weeks YGTSS Impairment CBIT > PST reduction in impairment from tics (51% vs. 30%, p < .01, d = 0.57)

Continued “Positive Responders” Evaluated at 3 months CBIT: 24/28 (85.7%) PST: 11/12 (91.7%)

Continued “Positive Responders” Evaluated at 6 months CBIT: 20/23 (86.9%) PST: 6/8 (75.0%)

Results

Available Treatments

CBIT RCT: YGTSS - ES = 0.57 – 0.68(Piacentini et al., 2010)

Dopamine Antagonists: ES = 0.58 Averse effects: sedation, cognitive dulling, weight gain, and metabolic

problems No significant differences on the efficacy of 4 antipsychotics tested

(haloperidol, pimozide, risperidone and ziprasidone)

Alpha-2 agonists: ES = 0.31

(ES = 0.68 w/ADHD; ES = 0.15 w/o ADHD) Averse effects: sedation and low blood pressure

(Weisman, Qureshi, Leckman, Scahill, & Bloch, 2013)

DSM-5 Model of Tourette Syndrome

Genetic & Physiological Factorso Risk alleleso Older paternal ageo Lower birth weighto Obstetrical complicationso Maternal smoking during

pregnancy

Environmental Factorso Perception by others



Secondary Featureso Premonitory Urgeso ADHD o OCD

Functional Consequenceso Social isolationo Interpersonal conflicto Peer victimizationo Inability to work/ go to schoolo Physical injury


New Model of Tourette SyndromeGenetic & Physiological Factorso Risk alleleso Lower birth weighto Maternal smoking during

pregnancyo PANDAS



Functional Consequenceso Social isolation (e.g., dating)o Interpersonal conflicto Peer victimizationo Inability to work/ go to schoolo Physical injuryo Perception by others

o GABAo DAo NE

o Cortico-striatal-

thalamic-circuito Sensorimotor cortex

Premonitory Urges

ADHD

OCD

Sleep Disorders

o Attentiono Aggression

Complex PhonicImpulse Control

Complex Motor

Simple Head Motor/Vocal

Simple Motor


Antipsychotics

CBIT

α-2 agonists

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Michael Gramlich Child Psychopathology Fall 2014 Tourette Syndrome (TS)

Documents

vocal tic disorder motor

exhaustion tics

tic onset

tourette syndrome ts

tourette syndrome criteria

combination of simple

functioning tic disorders

tic vulnerability