Tourette Syndrome (TS)
Michael Gramlich
Child Psychopathology
Fall 2014
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
DSM-5 Classification: “Neurodevelopmental Disorders”  “Motor 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
(American Psychiatric Association, 2013)
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

Coprolalia

Echopraxia

Copropraxia
HBO: Tourette Syndrome Clip
(American Psychiatric Association, 2013)
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
(American Psychiatric Association, 2013)
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
(American Psychiatric Association, 2013)
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)
(American Psychiatric Association, 2013)
Differential Diagnosis
Disorder
Description
Primary Difference
 Prolonged Duration
(seconds to minutes)
 Lack of a premonitory urge
Motor Stereotypies Involuntary, rhythmic,
repetitive, movements
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
(American Psychiatric Association, 2013)
DSM-5 Model of Tourette
Syndrome
Genetic & Physiological
Factors
o Risk alleles
o Older paternal age
o Lower birth weight
o Obstetrical complications
o Maternal smoking during
pregnancy
Exacerbating Factors
o Anxiety
o Excitement
o Exhaustion
o Stressful events
Alleviating Factors
o Focused activities
Core Features
o Motor Tics &
o Vocal Tics
Environmental Factors
o Perception by others
Functional Consequences
o Social isolation
o Interpersonal conflict
o Peer victimization
o Inability to work/ go to school
o Physical injury
Secondary Features
o Premonitory Urges
o ADHD
o OCD
Literature











Prevalence/Onset of TS
Clinical Features
Heritability + Genetics
Comorbidity
Risk Factors
Brain Structures
Neurotransmitters
Tic Suppression
Exacerbating/Alleviating Factors
Quality of Life
Treatment
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)
Coprophenomena
Freeman 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
TS = 8.7% (± 1.6%)
Controls
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
Twins
TS 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)
Genetics
Although 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: Functioning
Carter 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)
Results
(Carter et al., 2000)
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 firstdegree relatives.
(Cohen, Leckman, & Bloch, 2013)
(Bloch et al., 2006a)
Comorbid Sleep Disorders
Ghosh 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 Theory
Pediatric 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 Outcome
McGuire 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.
2.
3.
4.
5.




Number (0-5)
Frequency (0-5)
Intensity (0-5)
Complexity (0-5)
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].

Review






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).
Literature











Prevalence/Onset of TS
Clinical Features
Heritability + Genetics
Comorbidity
Risk Factors
Brain Structures
Neurotransmitters
Tic Suppression
Exacerbating/Alleviating Factors
Quality of Life
Treatment
Fine-motor Skills
Bloch, 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).
Structural Imaging: Basal
Ganglia
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
Results
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

(Peterson et al., 2003)
Structural Imaging: Basal
Ganglia
Bloch, 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
Results
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
(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.
Results
BOLD Signal Changes “Free”
Motor Tics
“Suppression” Events and Severity of
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.
(Peterson et al., 1998)
Structural Imaging:
Sensorimotor Cortices
Sowell et al. (2008)
 The average cortex in the
TS group was 0.45 mm thinner than
the controls.
 Age-by-diagnosis interaction where
cortices thickened with increasing age
in 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











Prevalence/Onset of TS
Clinical Features
Heritability + Genetics
Comorbidity
Risk Factors
Brain Structures
Neurotransmitters
Tic Suppression
Exacerbating/Alleviating Factors
Quality of Life
Treatment
Tic Suppression: Verbal
Instructions and Reinforcement
Woods and Himle (2004)
N = 4 (3 boys, 1 girl)
Token dispenser (“Tic detector”)
Remote controlled operant token
dispenser.
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 to
verbal instructions reduced tics
by 76%
 Consequences can affect tic
expression
BL: Baseline
VI: Verbal Instruction
DRO: Reinforced Suppression
“Tic Detector”
Premonitory Urges…
Negative Reinforcement?
Situational
Antecedents
Premonitory Urge
(unpleasant)
Expression of TIC
Termination of URGE
Figure by Piacentini J., “New Thoughts on Behavioral Treatment of Tourette Syndrome.”
February, 2006
Tic Suppression and
Premonitory Urge
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.
Results
10 Year Old Female
14 Year Old Male
17 Year Old Male
 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)
Development of Premonitory
Urge
Woods 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











Prevalence/Onset of TS
Clinical Features
Heritability + Genetics
Comorbidity
Risk Factors
Brain Structures
Neurotransmitters
Tic Suppression
Exacerbating/Alleviating Factors
Quality of Life
Treatment
Antecedents
Tics
Consequences

Happen immediately before
tics and make them more or
less likely to occur

Events after tics that make the
frequency or intensity of tics
more or less likely to happen

Internal (e.g., premonitory
urges, anxiety, or boredom)

Internal (e.g., embarrassment,
or relief from premonitory urge)

External (e.g., sports, the
presence of other people, or
being home from school)

External (e.g., attention from
family or peers, escape from
activities)
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).
Results
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
Impact of Attention on Tics
Conelea 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
Conditions
1.
2.
3.
Baseline (BL): tic freely, told tic detector was on but would not dispense tokens
Suppression (SUP): reinforced via tokens
Suppression and Distraction (SUP + DIS): reinforced via tokens + complete
auditory CPT
Results
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
(Conelea et al., 2008)
Impact of Stress on Tic
Frequencies
Conelea, 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”).
Conditions
1.
2.
3.
4.
Baseline (BL)
Reinforced Suppression (SUP)
Reinforced Suppression plus Stress Induction (SUP + STRESS)
Stress Induction (Stress)
- Each condition was 5 minutes, each condition was performed twice
Results
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
(Conelea et al., 2011)
Literature











Prevalence/Onset of TS
Clinical Features
Heritability + Genetics
Comorbidity
Risk Factors
Brain Structures
Neurotransmitters
Tic Suppression
Exacerbating/Alleviating Factors
Quality of Life
Treatment
Peer Relationships
Stokes, 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











Prevalence/Onset of TS
Clinical Features
Heritability + Genetics
Comorbidity
Risk Factors
Brain Structures
Neurotransmitters
Tic Suppression
Exacerbating/Alleviating Factors
Quality of Life
Treatment
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 Study
Piacentini 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
Results
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%)
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
Factors
o Risk alleles
o Older paternal age
o Lower birth weight
o Obstetrical complications
o Maternal smoking during
pregnancy
Exacerbating Factors
o Anxiety
o Excitement
o Exhaustion
o Stressful events
Alleviating Factors
o Focused activities
Core Features
o Motor Tics &
o Vocal Tics
Environmental Factors
o Perception by others
Functional Consequences
o Social isolation
o Interpersonal conflict
o Peer victimization
o Inability to work/ go to school
o Physical injury
Secondary Features
o Premonitory Urges
o ADHD
o OCD
New Model of Tourette Syndrome
Genetic & Physiological Factors
o Risk alleles
o Lower birth weight
o Maternal smoking during
pregnancy
o PANDAS
Exacerbating Factors
o Anxiety
o Excitement
o Exhaustion
o Stressful events
Alleviating Factors
o Focused activities
Complex Phonic
Impulse Control
Complex Motor
o GABA
o DA
o NE
Core Features
o Motor Tics &
o Vocal Tics
o Cortico-striatalthalamic-circuit
o Sensorimotor
cortex
Premonitory Urges
Antipsychotics
CBIT
Simple Head Motor/
Vocal
Simple Motor
Functional Consequences
o Social isolation (e.g., dating)
o Interpersonal conflict
o Peer victimization
o Inability to work/ go to school
o Physical injury
o Perception by others
Sleep Disorders
OCD
ADHD
α-2
agonists
o Attention
o Aggression
References















Azrin, N. H., & Nunn, R. G. (1973). Habit-reversal: a method of eliminating nervous habits and tics. Behav Res Ther, 11(4), 619-628.
Bloch, M. H., Leckman, J. F., Zhu, H., & Peterson, B. S. (2005). Caudate volumes in childhood predict symptom severity in adults with
Tourette syndrome. Neurology, 65(8), 1253-1258. doi: 10.1212/01.wnl.0000180957.98702.69
Bloch, M. H., Panza, K. E., Landeros-Weisenberger, A., & Leckman, J. F. (2009). Meta-analysis: treatment of attentiondeficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry, 48(9), 884-893. doi:
10.1097/CHI.0b013e3181b26e9f
Bloch, M. H., Peterson, B. S., Scahill, L., Otka, J., Katsovich, L., Zhang, H., & Leckman, J. F. (2006a). Adulthood outcome of tic and
obsessive-compulsive symptom severity in children with Tourette syndrome. Arch Pediatr Adolesc Med, 160(1), 65-69. doi:
10.1001/archpedi.160.1.65
Bloch, M. H., Sukhodolsky, D. G., Leckman, J. F., & Schultz, R. T. (2006b). Fine-motor skill deficits in childhood predict adulthood tic
severity and global psychosocial functioning in Tourette's syndrome. J Child Psychol Psychiatry, 47(6), 551-559. doi:
10.1111/j.1469-7610.2005.01561.x
Carter, A. S., O'Donnell, D. A., Schultz, R. T., Scahill, L., Leckman, J. F., & Pauls, D. L. (2000). Social and emotional adjustment in
children affected with Gilles de la Tourette's syndrome: associations with ADHD and family functioning. Attention Deficit
Hyperactivity Disorder. J Child Psychol Psychiatry, 41(2), 215-223.
Champion, L. M., Fulton, W. A., & Shady, G. A. (1988). Tourette syndrome and social functioning in a Canadian population. Neurosci
Biobehav Rev, 12(3-4), 255-257.
Chao, T. K., Hu, J., & Pringsheim, T. (2014). Prenatal risk factors for Tourette Syndrome: a systematic review. BMC Pregnancy Childbirth,
14, 53. doi: 10.1186/1471-2393-14-53
Cohen, S. C., Leckman, J. F., & Bloch, M. H. (2013). Clinical assessment of Tourette syndrome and tic disorders. Neurosci Biobehav
Rev, 37(6), 997-1007. doi: 10.1016/j.neubiorev.2012.11.013
Comings, D. E., Himes, J. A., & Comings, B. G. (1990). An epidemiologic study of Tourette's syndrome in a single school district. J
Clin Psychiatry, 51(11), 463-469.
Conelea, C. A., & Woods, D. W. (2008a). The influence of contextual factors on tic expression in Tourette's syndrome: a review. J
Psychosom Res, 65(5), 487-496. doi: 10.1016/j.jpsychores.2008.04.010
Conelea, C. A., & Woods, D. W. (2008b). Examining the impact of distraction on tic suppression in children and adolescents with Tourette
syndrome. Behav Res Ther, 46(11), 1193-1200. doi: 10.1016/j.brat.2008.07.005
Conelea, C. A., Woods, D. W., & Brandt, B. C. (2011). The impact of a stress induction task on tic frequencies in youth with Tourette
Syndrome. Behav Res Ther, 49(8), 492-497. doi: 10.1016/j.brat.2011.05.006
Freeman, R. D., Fast, D. K., Burd, L., Kerbeshian, J., Robertson, M. M., & Sandor, P. (2000). An international perspective on Tourette
syndrome: selected findings from 3,500 individuals in 22 countries. Dev Med Child Neurol, 42(7), 436-447.
Freeman, R. D., Zinner, S. H., Muller-Vahl, K. R., Fast, D. K., Burd, L. J., Kano, Y., . . . Berlin, C. M., Jr. (2009). Coprophenomena in
Tourette syndrome. Dev Med Child Neurol, 51(3), 218-227. doi: 10.1111/j.1469-8749.2008.03135.x
References















Ghosh, D., Rajan, P. V., Das, D., Datta, P., Rothner, A. D., & Erenberg, G. (2014). Sleep disorders in children with Tourette syndrome.
Pediatric Neurology, 51(1), 31-35. doi: 10.1016/j.pediatrneurol.2014.03.017
Hampson, M., Tokoglu, F., King, R. A., Constable, R. T., & Leckman, J. F. (2009) Brain areas coactivating with motor cortex during
chronic motor tics and intentional movements. Biological Psychiatry, 65, 594-599.
Himle, M. B., Woods, D. W., Conelea, C. A., Bauer, C. C., & Rice, K. A. (2007). Investigating the effects of tic suppression on premonitory
urge ratings in children and adolescents with Tourette's syndrome. Behav Res Ther, 45(12), 2964-2976. doi:
10.1016/j.brat.2007.08.007
Hyde, T. M., Aaronson, B. A., Randolph, C., Rickler, K. C., & Weinberger, D. R. (1992). Relationship of Birth-Weight to the PhenotypicExpression of Gilles-De-La-Tourettes Syndrome in Monozygotic Twins. Neurology, 42(3), 652-658.
Kalanithi, P. S., Zheng, W., Kataoka, Y., DiFiglia, M., Grantz, H., Saper, C. B., . . . Vaccarino, F. M. (2005). Altered parvalbumin-positive
neuron distribution in basal ganglia of individuals with Tourette syndrome. Proc Natl Acad Sci U S A, 102(37), 13307-13312.
doi: 10.1073/pnas.0502624102
Kataoka, Y., Kalanithi, P. S., Grantz, H., Schwartz, M. L., Saper, C., Leckman, J. F., & Vaccarino, F. M. (2010). Decreased number of
parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome. J Comp Neurol, 518(3), 277291. doi: 10.1002/cne.22206
Kenney, C., Hunter, C., & Jankovic, J. (2007). Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders.
Movement Disorders, 22(2), 193-197. doi: Doi 10.1002/Mds.21222
Khalifa, N., & von Knorring, A. L. (2006). Psychopathology in a Swedish population of school children with tic disorders. J Am Acad Child
Adolesc Psychiatry, 45(11), 1346-1353. doi: 10.1097/01.chi.0000251210.98749.83
Kurlan, R., McDermott, M. P., Deeley, C., Como, P. G., Brower, C., Eapen, S., . . . Miller, B. (2001). Prevalence of tics in schoolchildren
and association with placement in special education. Neurology, 57(8), 1383-1388.
Leckman, J. F. (2002). Tourette's syndrome. Lancet, 360(9345), 1577-1586. doi: 10.1016/S0140-6736(02)11526-1
Leckman, J. F., Bloch, M. H., Scahill, L., & King, R. A. (2006). Tourette syndrome: the self under siege. J Child Neurol, 21(8), 642-649.
Leckman, J. F., Bloch, M. H., Smith, M. E., Larabi, D., & Hampson, M. (2010). Neurobiological Substrates of Tourette's Disorder. Journal
of Child and Adolescent Psychopharmacology, 20(4), 237-247. doi: 10.1089/cap.2009.0118
Leckman, J. F., Walker, D. E., & Cohen, D. J. (1993). Premonitory urges in Tourette's syndrome. Am J Psychiatry, 150(1), 98-102. doi:
10.1176/ajp.150.1.98
Leckman, J. F., Zhang, H., Vitale, A., Lahnin, F., Lynch, K., Bondi, C., . . . Peterson, B. S. (1998). Course of tic severity in Tourette
syndrome: the first two decades. Pediatrics, 102(1 Pt 1), 14-19.
Lin, H., Katsovich, L., Ghebremichael, M., Findley, D. B., Grantz, H., Lombroso, P. J., . . . Leckman, J. F. (2007). Psychosocial stress
predicts future symptom severities in children and adolescents with Tourette syndrome and/or obsessive-compulsive disorder. J
Child Psychol Psychiatry, 48(2), 157-166. doi: 10.1111/j.1469-7610.2006.01687.x
References














Lin, H., Yeh, C. B., Peterson, B. S., Schahill, L., Grantz, H., Findley, D. B., Katsovich, L., Otka, J., Lombroso, P. J., King, R. A., &
Leckman, J. F. (2002). Assessment of symptom exacerbations in a longitudinal study of children with Tourette’s syndrome or
obsessive compulsive disorder. The American Academy of Child and Adolescent Psychiatry, 41(9), 1070-1077.
March, J. S., Franklin, M. E., Leonard, H., Garcia, A., Moore, P., Freeman, J., & Foa, E. (2007). Tics moderate treatment outcome with
sertraline but not cognitive-behavior therapy in pediatric obsessive-compulsive disorder. Biol Psychiatry, 61(3), 344-347. doi:
10.1016/j.biopsych.2006.09.035
McGuire, J. F., Nyirabahizi, E., Kircanski, K., Piacentini, J., Peterson, A. L., Woods, D. W., . . . Scahill, L. (2013). A cluster analysis of tic
symptoms in children and adults with Tourette syndrome: clinical correlates and treatment outcome. Psychiatry Res, 210(3),
1198-1204. doi: 10.1016/j.psychres.2013.09.021
McMahon, W. M., Carter, A. S., Fredine, N., & Pauls, D. L. (2003). Children at familial risk for Tourette's disorder: Child and parent
diagnoses. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics, 121B(1), 105-111. doi:
10.1002/Ajmg.B.20065
Mell, L. K., Davis, R. L., & Owens, D. (2005). Association between streptococcal infection and obsessive-compulsive disorder, Tourette's
syndrome, and tic disorder. Pediatrics, 116(1), 56-60. doi: 10.1542/peds.2004-2058
Mol Debes, N. M., Hjalgrim, H., & Skov, L. (2008). Validation of the presence of comorbidities in a Danish clinical cohort of children with
Tourette syndrome. J Child Neurol, 23(9), 1017-1027. doi: 10.1177/0883073808316370
Murphy, T. K., Kurlan, R., & Leckman, J. (2010). The immunobiology of Tourette's disorder, pediatric autoimmune neuropsychiatric
disorders associated with Streptococcus, and related disorders: a way forward. J Child Adolesc Psychopharmacol, 20(4), 317331. doi: 10.1089/cap.2010.0043
O'Rourke, J. A., Scharf, J. M., Yu, D., & Pauls, D. L. (2009). The genetics of Tourette syndrome: a review. J Psychosom Res, 67(6), 533545. doi: 10.1016/j.jpsychores.2009.06.006
Pauls, D. L., Raymond, C. L., Stevenson, J. M., & Leckman, J. F. (1991). A family study of Gilles de la Tourette syndrome. Am J Hum
Genet, 48(1), 154-163.
Peterson, B. S., & Leckman, J. F. (1998). The Temporal dynamics of tics in Gilles de la Tourette syndrome. Biological Psychiatry, 44(12),
1337-1348.
Peterson, B. S., Skudlarski, P., Anderson, A. W., Zhang, H., Gatenby, J. C., Lacadie, C. M., . . . Gore, J. C. (1998). A functional magnetic
resonance imaging study of tic suppression in Tourette syndrome. Arch Gen Psychiatry, 55(4), 326-333.
Peterson, B. S., Thomas, P., Kane, M. J., Scahill, L., Zhang, H., Bronen, R., . . . Staib, L. (2003). Basal Ganglia volumes in patients with
Gilles de la Tourette syndrome. Arch Gen Psychiatry, 60(4), 415-424. doi: 10.1001/archpsyc.60.4.415
Piacentini, J., Woods, D. W., Scahill, L., Wilhelm, S., Peterson, A. L., Chang, S., . . . Walkup, J. T. (2010). Behavior therapy for children
with Tourette disorder: a randomized controlled trial. JAMA, 303(19), 1929-1937. doi: 10.1001/jama.2010.607
Price, R. A., Kidd, K. K., Cohen, D. J., Pauls, D. L., & Leckman, J. F. (1985). A twin study of Tourette syndrome. Arch Gen Psychiatry,
42(8), 815-820.
References











Robertson, M. M. (2008). The prevalence and epidemiology of Gilles de la Tourette syndrome. Part 1: the epidemiological and prevalence
studies. J Psychosom Res, 65(5), 461-472. doi: 10.1016/j.jpsychores.2008.03.006
Scahill, L., Erenberg, G., Berlin, C. M., Jr., Budman, C., Coffey, B. J., Jankovic, J., . . . Tourette Syndrome Association Medical Advisory
Board: Practice, C. (2006). Contemporary assessment and pharmacotherapy of Tourette syndrome. NeuroRx, 3(2), 192-206.
doi: 10.1016/j.nurx.2006.01.009
Scharf, J. M., Yu, D., Mathews, C. A., Neale, B. M., Stewart, S. E., Fagerness, J. A., . . . Pauls, D. L. (2013). Genome-wide association
study of Tourette's syndrome. Mol Psychiatry, 18(6), 721-728. doi: 10.1038/mp.2012.69
Sowell, E. R., Kan, E., Yoshii, J., Thompson, P. M., Bansal, R., Xu, D., . . . Peterson, B. S. (2008). Thinning of sensorimotor cortices in
children with Tourette syndrome. Nat Neurosci, 11(6), 637-639. doi: 10.1038/nn.2121
Stokes, A., Bawden, H. N., Camfield, P. R., Backman, J. E., & Dooley, J. M. (1991). Peer problems in Tourette's disorder. Pediatrics,
87(6), 936-942.
Sullivan, P. F. (2010). The psychiatric GWAS consortium: big science comes to psychiatry. Neuron, 68(2), 182-186. doi:
10.1016/j.neuron.2010.10.003
Tourette Syndrome Association International Consortium for, G. (2007). Genome scan for Tourette disorder in affected-sibling-pair and
multigenerational families. Am J Hum Genet, 80(2), 265-272. doi: 10.1086/511052
Weisman, H., Qureshi, I. A., Leckman, J. F., Scahill, L., & Bloch, M. H. (2013). Systematic review: pharmacological treatment of tic
disorders--efficacy of antipsychotic and alpha-2 adrenergic agonist agents. Neurosci Biobehav Rev, 37(6), 1162-1171. doi:
10.1016/j.neubiorev.2012.09.008
Woods, D. W., & Himle, M. B. (2004). Creating tic suppression: comparing the effects of verbal instruction to differential reinforcement. J
Appl Behav Anal, 37(3), 417-420. doi: 10.1901/jaba.2004.37-417
Woods, D. W., Piacentini, J., Himle, M. B., & Chang, S. (2005). Premonitory Urge for Tics Scale (PUTS): initial psychometric results and
examination of the premonitory urge phenomenon in youths with Tic disorders. J Dev Behav Pediatr, 26(6), 397-403.
Woods, D. W., Walther, M. R., Bauer, C. C., Kemp, J. J., & Conelea, C. A. (2009). The development of stimulus control over tics: a
potential explanation for contextually-based variability in the symptoms of Tourette syndrome. Behav Res Ther, 47(1), 41-47.
doi: 10.1016/j.brat.2008.10.013