Ticked Off Anger Outbursts and Aggressive Symptoms in Tourette Disorder
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Ticked Off
Anger Outbursts and Aggressive Symptoms in
Tourette Disorder
Marianna Ashurova, MDa,b,*, Cathy Budman, MD
c,d
,
Barbara J. Coffey, MD, MSe
KEYWORDS
Rage in Tourette disorder Explosive outbursts in Tourette disorder
Aggressive symptoms in Tourette disorder
Disruptive behaviors in Tourette disorder
KEY POINTS
Explosive outbursts (rage) are common symptoms of impulsive aggression in Tourette
disorder.
Explosive outbursts often are associated with tic severity and psychiatric comorbidity in
Tourette disorder.
Explosive outbursts in Tourette disorder cause significant morbidity and require compre-
hensive evaluation with targeted treatments.
BACKGROUND
Aggression is a complex construct encompassing a range of different internal pro-
cesses and external manifestations. The term, aggression, is applied to an array of
different symptoms, behaviors, and experiences, some considered developmentally
and/or socially appropriate, whereas others are regarded as maladaptive and patho-
logic. Aggressive symptoms and behavioral and emotional dysregulation are frequent
reasons for referral to mental and behavioral health services and are among the core
symptoms in several psychiatric disorders, including intermittent explosive disorder,
a
Zucker Hillside Hospital, ACP Building Basement, 75-59 263rd Street, Glen Oaks, NY 11004,
USA; b Child & Adolescent Psychiatry Consultation Liaison Service, Cohens Children’s Medical
Center, 268-01 76th Avenue, New Hyde Park, NY 11040, USA; c Long Island Center for Tourette,
1615 Northern Boulevard, Suite #306, Manhasset, NY 11030, USA; d Zucker School of Medicine,
500 Hofstra Boulevard, Hempstead, NY 11549, USA; e Department of Psychiatry and Behavioral
Sciences, Child and Adolescent Psychiatry, Tourette Association Center of Excellence, University
of Miami Miller School of Medicine, 1120 Northwest Fourteenth Street, Suite 1442, Miami, FL
33136, USA
* Corresponding author.
E-mail address: cbudmanmd@gmail.com
Child Adolesc Psychiatric Clin N Am - (2020) -–-
https://doi.org/10.1016/j.chc.2020.10.006 childpsych.theclinics.com
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disruptive mood dysregulation disorder, oppositional defiant disorder (ODD), and
conduct disorder.1,2 The most common aggressive symptoms in clinically referred
children are impulsive in nature and associated with substantial functional impairment
for the individual, family, and community.3–8
GENERAL FEATURES OF TOURETTE DISORDER
Tourette disorder (TD) is a neurodevelopmental disorder characterized by multiple re-
petitive movements (ie, motor tics) and at least 1 repetitive sound or vocalization (ie,
phonic tic) that persist (not necessarily concurrently) for at least 1 year. Tics charac-
teristically wax and wane in severity, change in type and in location, and are not
due to any other underlying medical condition or substance.2 Tics typically begin be-
tween 4 years and 6 years of age, peak in severity at 10 years to 12 years, and often
decline during mid to late adolescence.9 TD occurs worldwide and is reported more
frequently in boys than girls.10
Whereas its exact prevalence is uncertain, TD is estimated to occur in approxi-
mately 0.52% to 0.77% of youth.11 Chronic motor tic disorder, which may represent
a milder form of TD, appears to be approximately twice as prevalent.12,13 TD is one
of the most heritable but heterogeneous neuropsychiatric disorders of childhood,
resulting from a complex interplay between both genetic and environmental
factors.14,15
Co-occurring psychiatric conditions are extremely common in TD and are associ-
ated with greater overall morbidity and lowered quality of life.16–21 Approximately
90% of youth with TD have been reported to have at least 1 or more psychiatric con-
ditions, including obsessive-compulsive disorder (OCD), attention-deficit/
hyperactivity disorder (ADHD) (with 72.1% of people with TD having both OCD and
ADHD), mood disorders (30%), non-OCD anxiety disorders (30%) and other impulse
control problems, sleep disturbances, and school and social problems.21–24
ANGER OUTBURSTS AND AGGRESSIVE SYMPTOMS IN TOURETTE DISORDER
Excessive anger and aggressive symptoms have been reported in 25% to 70% of in-
dividuals with TD worldwide.25–27 In an international survey of 3500 outpatients with
TD, 37% reported a lifetime history of anger control problems and 25% experienced
current anger problems.28 Among youth with TD, such symptoms range in their inten-
sity from persistent angry verbal protests and intense argumentativeness to more se-
vere outbursts of verbal and/or physical aggression (ie, rage attacks or explosive
outbursts). Aggressive behavior is grossly out of proportion to any stressor, is highly
destructive to relationships and physical property, typically is directed at the primary
caregiver, and may vary in duration from minutes to hours.29–31 The aggressive out-
bursts occur mostly at home rather than in school or other settings.25,31 Major life
events (ie, being bullied, severe parental conflict, or parental divorce) that influence
tic expression and severity also are linked with aggressive symptoms in TD.32
Common precipitants include failing to get one’s way, experiencing unforeseen
frustration or change in plans, and being reprimanded, criticized, or cor-
rected.25,30,33,34 Explosive outbursts also may be triggered by a cognitive or sensory
urge or discomfort.30 Family members typically experience these sudden angry be-
haviors as shocking and escalating with lightning speed; the angry responses are
age-inappropriate, unpredictable, intense, excessive, and irrational.30,31 Those expe-
riencing these sudden fits of anger describe feeling “out of control” and are acutely
distressed; most show signs of heightened physiologic arousal, including increased
heart rate and psychomotor agitation. A majority of explosive outbursts are impulsive
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and reactive in nature; afterward, the individual often experiences feelings of
increased physical/emotional calm and remorse. In contrast, predatory or proactive
aggression is characterized by deliberate, planned, goal-directed behaviors with
low autonomic arousal.33,35,36
DEVELOPMENTAL COURSE
The onset of anger control problems in TD typically occurs during early childhood and
may persist into adolescence and adulthood.37,38 These symptoms are a major cause
of morbidity in TD and are associated with increased family stress and conflict;
impaired social, academic, and occupational functioning; and increased rates of psy-
chiatric hospitalization.30,39–44
The etiology of anger control problems in TD is multifactorial, stemming from a com-
bination and synergism of biopsychosocial factors.30,32,39,42 Tic complexity and
severity, for example, correlate with worsening irritability and with a stronger associ-
ation to vocal rather than motor tics.18 Tic severity also contributes to worsening
school performance, impaired social functioning, and reduced overall quality of
life.45–47 Psychiatric comorbidities, in particular ADHD, OCD, and mood disorders,
are highly and significantly associated with aggression in TD as
well.26,27,29,33,34,48–50 Some studies comparing those with TD and OCD, with or
without ADHD, found that ADHD is the main predictor of disruptive behaviors in TD
as well as the main explanatory factor for lack of inhibitory control.51–53 Untangling in-
teractions among psychiatric comorbidities and their symptoms and evaluating func-
tional consequences of different tic types, complexities, and severities, along with
considering how varying psychosocial stresses have an impact over the course of
development, pose major challenges for clinical assessment and management.
CLINICAL CORRELATES OF AGGRESSIVE SYMPTOMS IN TOURETTE DISORDER
Early studies that explored the phenomenology of explosive outbursts in clinically
referred youth with TD reported an apparent association with underlying psychiatric
comorbidity, in particular comorbid ADHD and/or OCD.25,30,50,54–56
In a study of 113 clinically referred youth with TD, ages 7 years to 17 years, 48 (43%)
subjects with rage attacks were more likely to meet current Diagnostic and Statistical
Manual of Mental Disorders (Fourth Edition) criteria for major depression, depression
not otherwise specified, bipolar I disorder, ADHD, and ODD, and lifetime criteria for
OCD and/or ODD than the 65 comparison subjects without explosive outbursts.30
An investigation of 218 TD-affected individuals who participated in a genetic study
(N 5 104 from a nonclinical sample in Costa Rica, and N 5 114 recruited from spe-
cialty US TD clinics) examined the prevalence and clinical correlates of explosive out-
bursts; 20% of all TD-affected individuals had explosive outbursts, with no significant
differences in prevalence between the nonclinical and the clinical samples. In the over-
all sample, ADHD, greater tic severity, and lower age of tic onset were associated
strongly with explosive outbursts. ADHD, male gender, and prenatal exposure to to-
bacco were significantly associated with explosive outbursts in the clinical sample,
whereas lower age of onset and greater severity of tics were significantly associated
with explosive outbursts in the nonclinical sample.29
A large study of 578 clinically referred individuals with TD showed a significant as-
sociation between tic severity and current aggressive behaviors.39 An association be-
tween tic severity and higher levels of irritability also was demonstrated in a clinical
study of 101 patients with TD.18 More recently, however, a clinical study of 47 youth
ages 7 years to 17 years with TD from a tertiary pediatric Tourette clinic compared
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with a group of 32 healthy age-matched and sex-matched controls found no signifi-
cant differences in aggression scores measured by the Overt Aggression Scale, and
levels of aggression were not correlated with tic severity.48 In this study, verbal
aggression occurred in 70% of the youth with TD and was the most prevalent type.
Although the probability of aggression in the TD cohort was increased by comorbid
ADHD and OCD, only ADHD severity emerged as a significant predictor of
aggression.35
NEUROBIOLOGICAL INFLUENCES ON AGGRESSIVE SYMPTOMS IN TOURETTE
DISORDER
Studies in the non–TD-disordered population show that aggressive symptoms are
influenced by interconnected circuitry that integrates activities associated with
arousal, impulse control, motivation, memory, affect regulation, and sensory and so-
cial processing.57 Aggression dyscontrol may be the consequence of exaggerated ac-
tivity in the subcortical circuits that mediate adaptive aggressive behaviors because
they are triggered by endogenous or environmental cues at vulnerable time points
or may be due to disturbed activity within multiple converging cortical and subcortical
circuits; aggression also is shaped by social context and repeated environmental
reward/reinforcement.57,58 Evidence from neuroimaging studies of intermittent explo-
sive disorder in adults suggests simultaneous hypofunction of the medial prefrontal
cortex and hyperfunction of the amygdala.59 Failure of top-down cognitive control
may be common to TD, OCD, and ADHD.60 Disturbances of circadian rhythms and ab-
normalities of neurotransmission involving dopamine, serotonin, norepinephrine, and
glutamate g-aminobutyric acid neurotransmission in the prefrontal cortex as well as
low testosterone and elevated cortisol have been associated with impulsive aggres-
sion.61–66 A recent study of 55 patients with TD and explosive outbursts using a multi-
modal neuroimaging approach found structural changes in the right supplementary
motor area as well as in the right hippocampus and in the left orbitofrontal cortex, sug-
gesting lower connectivity within the sensorimotor cortico-basal ganglia network and
aberrant connectivity pattern among the orbito-fontal cortex, amygdala, and
hippocampus.67
EVALUATION AND DIFFERENTIAL DIAGNOSIS OF AGGRESSIVE SYMPTOMS IN
TOURETTE DISORDER
Comprehensive evaluation of the individual with TD and aggressive symptoms is indi-
cated. Multidisciplinary evaluation is helpful, given the clinical complexity of these
cases. Detailed history should include developmental, medical, and behavioral symp-
toms and conditions; family, social, and trauma background; alcohol and substance
use; prescribed, over-the-counter medications and supplements; accidental or inten-
tional toxic exposures; and psychosocial history and identifiable triggers68 (Table 1).
Once underlying medical conditions and specific psychosocial triggers are
excluded, the presence and severity of comorbid psychiatric disorders, in particular
ADHD, OCD, and mood disorders, must be carefully explored. Other co-occurring
psychiatric conditions should be considered, including autistic spectrum disorder,
ODD, conduct disorder, posttraumatic stress disorder, borderline personality disor-
der, specific learning disorders, and specific impulse control disorders.
Self-injurious behaviors (SIBs), such as pinching, slapping, biting, poking, and
head-banging, that result in moderate to severe injury may occur up to 60% of all
patients with TD and may be associated increased tic severity, copra phenomena,
high levels of obsessiveness and hostility, OCD, ADHD, increased numbers and
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Table 1
Differential diagnosis of aggression in youth with Tourette disorder
Causes Clinical Examples
Metabolic encephalopathies Hyperthyroidism, primary hyperparathyroidism
Infectious encephalopathies Pediatric autoimmune neuropsychiatric symptoms
Autoimmune encephalopathies Systemic lupus erythematosus (SLE),
N-methyl-D-aspartate receptor encephalitis,
Beçet syndrome
Traumatic brain injury Postconcussive syndromes, head trauma
Seizure disorder Partial complex seizures
Movement disorders Wilson disease, Huntington disease
Acute intoxications/withdrawal states Lead poisoning, alcohol intoxication, steroid
abuse
Accidental/deliberate poisoning Prescribed medication overdose
Medication side effects/interactions Acute akathisia, antidepressant activation
Parasomnias Night terrors
Physical pain Injury secondary to tics
Sexual, physical, emotional abuse Rape, trauma, bullying
Other psychosocial problems Family conflict
severity of psychiatric disorders, episodic rages, affective dysregulation, and severe
impulsivity.39,69–73 Severe SIBs occur in only 5% of all TD cases.74
A recent clinical study of 165 consecutive patients ages 5 years to 50 years revealed
a lifetime history of self-harming behaviors (SHBs) in 39.4%. In this sample, ADHD and
OCD were found to be risk factors for lifetime SHBs, whereas only tic severity emerged
as a statistically significant risk factor for current and lifetime SHBs in children. Anxiety
and other psychiatric comorbidities, but not tic severity, was associated with SHBs in
adults.75
ENVIRONMENTAL INFLUENCES ON AGGRESSIVE SYMPTOMS IN TOURETTE
DISORDER
Usually the adverse impact on quality of life from TD is linked more closely with psy-
chosocial and environmental factors than with tics themselves.76,77 Many with TD and
its co-occurring conditions struggle to attain competency and confidence in navi-
gating normal age-appropriate development, family relationships, peer attachment,
and academic and occupational performance.78,79 A comparative study showed
that parents of children with TD experience greater aggravation than parents of chil-
dren without TD; parents who report being bothered by tics and rage symptoms are
more likely to punish their children.80,81 An authoritative parenting style with unrealistic
expectations and minimal support negatively reinforces tics and aggression.78 Con-
flict avoidance, failure to set appropriate expectations and limits, and family accom-
modation of OCD symptoms and/or tics also reinforce aggression.82
TREATMENT STRATEGIES FOR AGGRESSIVE SYMPTOMS IN TOURETTE DISORDER
Psychosocial Interventions
Considerable evidence supports the efficacy of behavioral interventions for reduction
of aggressive behaviors in children with/without tic disorders. These include parent
guidance or coaching therapy, teacher training, behavioral modification, and pro-
grams addressing skills deficits/issues within a patient-centered approach.49,83
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Psychoeducation and parent and teacher training are particularly important, because
parents, siblings, school staff, peers, health care providers, and others struggle to un-
derstand which behaviors of TD are deliberate or intentional and which are tics, com-
pulsions, impulsive-compulsive symptoms, or medication side effects.49,84,85
Diminished parental expectations for their children’s self-control may be over-
generalized, leading to increased disruptive behaviors.84 Family accommodation of
tics and/or OCD symptoms occurs frequently and is associated with greater levels
of overall functional impairment.86,87 A study of children with OCD ages 6 years to
16 years showed that rage impaired quality of life out of proportion to OCD symptoms
alone. This impairment was explained by family accommodation, resulting in either
worsening rage and/or rage promoting increased familial accommodation.87 In a study
of youth ages 6 years to 18 years with tic disorder, 68% of parents of children with TD
endorsed some form of tic accommodation during the month prior to study participa-
tion.86 Family accommodation likely plays a significant role in fueling or contributing to
explosive outbursts in TD as well.
How parental psychopathology and family expressed or repressed emotion also
triggers and fuels explosive outbursts in youth with TD requires further consideration.
Because TD is highly heritable, the likelihood that a parent(s) and/or siblings may suffer
from tics and/or co-occurring psychiatric comorbidities is high. Therefore, screening,
identifying, and treating psychopathology in family members of youth with TD with
rage symptoms are imperative.
Providing the necessary parental psychoeducation and skills to better understand
and manage their child’s often puzzling behaviors has demonstrated significant effi-
cacy for managing explosive outbursts in youth with TD. A randomized controlled trial
of parent management training versus treatment as usual in youth with tic disorders
and disruptive behaviors comparing 10 sessions of parent training (including psycho-
education about tics and co-occurring symptoms, limit and expectation setting, time-
outs, and positive reinforcement) demonstrated a 51% decline in disruptive behaviors
versus 19% in the treatment as usual, with a reported effect size of 0.96, comparable
to that achieved by parent training for non–tic-associated ODD.81The clinical
approach “brief trans-diagnostic parent training,” also has demonstrated treatment
efficacy for children with TD and aggression.88
Cognitive behavior therapy appears moderately effective in reducing anger and
aggression in children without tic disorders and may have application for those with
TD.89–93 Treatment focuses on improving awareness of behavioral patterns and asso-
ciated emotions and cognitions.93
A study that investigated anger control training (ACT) in adolescents with TD be-
tween the ages of 11 years and 16 years randomized subjects with ODD to receive
either ACT or treatment as usual for 10 weeks. Among those who received ACT (ie,
10, 1-hour–long sessions that included managing anger, cognitive restructuring, and
behavioral interventions), 52% demonstrated a reduction in disruptive behavior
compared with an 11% reduction in the treatment as usual control group; these im-
provements were sustained at 3 month follow-up.49 Additional studies are necessary
to ascertain which treatment interventions are most useful at certain ages and with
which particular clinical subtypes of TD.
Psychopharmacologic Interventions
Atypical antipsychotics
A majority of individuals with TD do not require pharmacologic intervention for tic sup-
pression alone; however, depending on aggression severity, medication intervention
may become more immediate, particularly when aggression occurs in more than 1
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setting.94 Atypical antipsychotics, such as aripiprazole and olanzapine, have been
used to treated combined TD and aggression.34,95 These agents, however, may cause
serious adverse effects, including acute dystonic reactions, parkinsonism, akathisia,
neuroleptic malignant syndrome, acute dystonia, weight gain, and risks for metabolic
syndrome.34,96 Nonetheless, when there is urgency to address severe, recurrent rage,
particularly if accompanied by severe tics, unstable mood, severe OCD, and anxiety,
use of atypical antipsychotics on at least an acute basis may be necessary.
Stimulants and a-agonists
ADHD is 1 of the 2 most frequently comorbid disorders with TD yet may be under-
recognized and undertreated. This is of particular concern because many clinicians
still avoid use of psychostimulants for treatment of combined ADHD and tics due to
unwarranted concerns that these agents are contraindicated in TD. Treatment of TD
with comorbid ADHD is particularly important, because both disruptive behavior
and tic severity may be reduced when ADHD symptoms are treated.97
Tics, ADHD symptoms, and aggressive behaviors have been shown to improve by
treatment with a-agonists (such as clonidine and guanfacine), psychostimulants, and
targeted combined pharmacotherapy with an a-agonist and psychostimulant.98–100
Youth with comorbid TD and ADHD who are treated with psychostimulants show an
overall reduction of aggression and antisocial behavior.35,101,102 Short-acting methyl-
phenidate was found effective in treating oppositional behavior and peer aggression in
children with ADHD and TD.103 a-Agonists also have been reported to decrease irrita-
bility and aggression in conduct disorder co-occurring with TD.104 When a-agonists
are used to treat tics in TD without ADHD, treatment effect size is reduced.98,99
Selective serotonin inhibitors
Treatment of youth with OCD, tic, and rage attacks with serotonin reuptake inhibitors
(SRIs) may be beneficial.56 In an open-label study of paroxetine in 45 children with TD
and explosive outbursts, 76% demonstrated reduced rage symptoms using an
average dose of 33 mg/d. A majority of subjects met diagnostic criteria for OCD,
ADHD, or both. However, 4 subjects experienced worsening of rage outbursts, and
1 subject experienced a hypomanic episode.54 Using SRIs for treatment of rage re-
quires close monitoring for adverse effects, such as activation, hypomania, and
aggression.105 Larger, randomized controlled studies are needed to confirm efficacy
of these agents for treatment of explosive outbursts in TD.
SUMMARY
TD is a complex neurodevelopmental disorder characterized by multiple motor and
phonic tics and is associated with high rates of psychiatric comorbidity. Symptoms
of impulsive aggression commonly are encountered in the clinical setting, cause sig-
nificant morbidity, and pose considerable diagnostic and treatment challenges. These
symptoms usually are multifactorial in etiology and result from a complex interplay of
illness severity and psychosocial factors, including tic severity, comorbid psychiatric
disorders, and family accommodation of aggression. Treatment strategies require
comprehensive evaluation and include both behavioral and pharmacologic interven-
tions. More research is needed in this important area of scientific, clinical, and public
health significance.
DISCLOSURE
The authors have nothing to disclose.
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