Chapter 44. Tourette Disorder and Obsessive–Compulsive Disorder in Children and Adolescents

Essentials of Diagnosis

DSM-IV-TR Diagnostic Criteria

Tourette's Disorder

1. Both multiple motor and one or more vocal tics have been present at some time during the illness, although not necessarily concurrently. (A tic is a sudden, rapid, recurrent, nonrhythmic, stereotyped motor movement or vocalization.)

2. The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout a period of more than 1 year, and during this period there was never a tic-free period of more than 3 consecutive months.

3. The onset is before age 18 years.

4. The disturbance is not due to the direct physiological effects of a substance (e.g., stimulants) or a general medical condition (e.g., Huntington's disease or postviral encephalitis).

Chronic Motor or Vocal Tic Disorder

1. Single or multiple motor or vocal tics (i.e., sudden, rapid, recurrent, nonrhythmic, stereotyped motor movements or vocalizations), but not both, have been present at some time during the illness.

2. The tics occur many times a day nearly every day or intermittently throughout a period of more than 1 year, and during this period there was never a tic-free period of more than 3 consecutive months.

3. The onset is before age 18 years.

4. The disturbance is not due to the direct physiological effects of a substance (e.g., stimulants) or a general medical condition (e.g., Huntington's disease or postviral encephalitis).

5. Criteria have never been met for Tourettes Disorder.

Transient Tic Disorder

1. Single or multiple motor and/or vocal tics (i.e., sudden, rapid, recurrent, nonrhythmic, stereotyped motor movements or vocalizations)

2. The tics occur many times a day, nearly every day for at least 4 weeks, but for no longer than 12 consecutive months.

3. The onset is before age 18 years.

4. The disturbance is not due to the direct physiological effects of a substance (e.g., stimulants) or a general medical condition (e.g., Huntington's disease or postviral encephalitis).

5. Criteria have never been met for Tourettes Disorder or Chronic Motor or Vocal Tic Disorder.

Tic Disorder Not Otherwise Specified

This category is for disorders characterized by tics that do not meet criteria for a specific Tic Disorder. Examples include tics lasting less than 4 weeks or tics with an onset after age 18 years.

(Adapted with permission from Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Text Revision. Copyright 2000 American Psychiatric Association.)

General Considerations

Epidemiology

Transient tic behaviors are commonplace among school-age children. Estimates range between 4% and 24% of school-age children experiencing tics. The number of children experiencing chronic motor tic disorders is roughly one-quarter this number. Once thought to be much rarer, the current lifetime prevalence estimates for TS ranges from 0.1% to 1%.

The prevalence of tic disorders peaks during the late first and early second decades of life due to the clinical course of the disorder. They are roughly one-third as prevalent in adulthood. Boys are about twice as likely to be affected by tic disorders as girls.

Etiology

The current understanding of Tourette syndrome (TS) provides a good working model for understanding the pathogenesis of other childhood neuropsychiatric disorders: a genetically determined vulnerability, age-dependent expression of symptoms reflecting maturational factors, sexual dimorphism, stress-dependent fluctuations in symptom severity, and environmental influences on the phenotypical expression of the tic.

Strong evidence implicates the basal ganglia and corticostriatal−thalamocortical (CSTC) abnormalities as central to the pathogenesis of tics. Indirect evidence for the involvement of the basal ganglia in the pathogenesis of TS comes from the association with basal ganglia pathology of other movement disorders such as Sydenham's chorea, Huntington's disease, hemiballismus and Parkinson's disease. Direct evidence supporting CSTC abnormalities in TS comes from neuroimaging, neuropathological and neurosurgical studies.

CSTC loops are multiple, parallel, but partially overlapping, neuroanatomical circuits, relaying information from most regions of the cortex to subcortical areas, particularly the striatum and thalamus, which in turn project to a subset of the original cortical areas. In CSTC loops, the basal ganglia can be viewed as a way station between intention and action (thought, affect and movement). Tics, repetitive and stereotyped movements are believed to arise from imbalances in focal populations in the basal ganglia circuits. A tic may arise through failure of inhibition of a discrete population of striatal projection neurons which become abnormally active and cause an unwanted disinhibition of a corresponding group of thalamocortical projection neurons. Thus a cortical motor pattern generator is activated so that unintended urges and motor and vocal tics are triggered.

Altered dopaminergic functioning has also been strongly implicated in the pathogenesis of TS. Evidence for abnormal dopamine neurotransmission in TS is inferred from two clinical observations. First, blockade of dopamine receptors by neuroleptic drugs suppresses tics in a majority of patients. In addition, dopamine-releasing drugs such as cocaine and amphetamines have been reported to precipitate or exacerbate tics. It has been shown that TS patients release more dopamine at dopaminergic synapses in response to amphetamine. Second, the importance of dopamine in TS is supported by brain imaging using dopamine ligands in single photon emission computed tomography and positron emission tomography. In one twin study, tic severity was related to dopamine D2 receptor binding in the head of the caudate nucleus.

Genetics

Although the particular genetic factors responsible for TS remain largely undiscovered, there is a sizable heritable component responsible for this illness. Early twin studies have suggested that the concordance rate for TS among monozygotic twin pairs is greater than 50% while the concordance of dizygotic twin pairs is about 10%. If twins with chronic motor tic disorder are included, concordance figures increase to 77% for monozygotic and 30% for dizygotic twin pairs. Differences in the concordance of monozygotic and dizygotic twin pairs indicate that genetic factors play an important role in the etiology of TS and related conditions. These figures also suggest that nongenetic factors are critical in determining the nature and severity of the clinical syndrome.

The overall risk that an offspring of a parent with TS will develop TS is approximately 10–15%, while the risk of offspring developing a tic disorder (20–29%) or obsessive–compulsive disorder (OCD) (12–32%) is slightly higher. The risk of developing tic disorders in male offspring is higher than for females, while the risk of developing OCD is lower.

Recently, an analysis of a chromosomal anomaly in one TS patient led to the identification of two sequence variants in the SLITRK1 gene in approximately 1% of TS cases. Specifically, among 174 unrelated probands with TS, one frameshift mutation and two identical variants in the 3′ untranscribed region of this gene were identified. None of these anomalies was demonstrated in over 3,600 controls. SLITRK1 mRNA is expressed in the human fetal brain at 20 weeks gestation in multiple neuroanatomical areas implicated in TS neuropathology including the cortical plate, striatum, globus pallidus, thalamus and subthalamic nucleus. While other genes of major effect are likely to be found, it is becoming ever clear that TS is likely to be a polygenetic disorder with complex gene–environment interactions that have yet to be fully elucidated.

Environmental Factors

The existence of monozygotic twins discordant for tic severity emphasizes the importance of environmental factors in the phenotypic expression of TS. In monozygotic twins discordant for tic severity, the twin with more severe tics has usually had the lower birth weight and has a greater number of dopamine receptor sites in the caudate nucleus. In observational and case control studies, low (Activity, Pulse, Grimace, Appearance, and Respiration); APGAR scores, stressful maternal life circumstances during pregnancy and maternal first-trimester nausea are risk factors for TS.

Tic disorders have long been identified as “stress-sensitive” conditions. Typically, symptom exacerbations follow in the wake of stressful life events. These events need not be adverse in character. Clinical experience suggests that in some unfortunate instances a vicious cycle can be initiated in which tic symptoms are misunderstood by the family and teachers, leading to active attempts to suppress the symptoms by punishment and humiliation. These efforts can lead to a further exacerbation of symptoms and an increase in stress in the child's interpersonal environment. Prospective longitudinal studies have begun to examine systematically the effect of intramorbid stress. These studies indicate that patients with TS experience more stress than matched healthy controls and that antecedent stress may play a role in subsequent tic exacerbations.

Post-infectious autoimmune mechanisms have been implicated in a small number of post-streptococcal cases of TS and OCD known as Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal (PANDAS) infections. PANDAS cases are characterized by a sudden onset of symptoms, episodic course, and abrupt symptom exacerbations, sometimes accompanied by adventitious movements. The most salient differentiating factor between PANDAS and other cases of TS and OCD is an exacerbation of OCD and tic symptoms accompanied by positive streptococcal throat cultures, increased antistreptoccal and antineuronal antibodies, but no evidence of rheumatic fever. Evidence that PANDAS and post-streptococcal autoimmune factors are associated with some cases of tics and OCD comes from a variety of sources. Sydenham's chorea, a late autoimmune sequela of rheumatic fever, is often accompanied by tics, mood changes, OCD, attention-deficit hyperactivity disorder (ADHD) and anxiety. There is a large series of over 50 children in whom exacerbations of OCD or tics were accompanied by positive streptococcal throat cultures and increased antistreptoccal and antineuronal antibodies without evidence of rheumatic fever. One case-control study found an increased proportion of group A β-hemolytic streptococcal (GABHS) infections (odds ratio = 3.05) within the preceding 3 months in children newly-diagnosed with TS compared to well-matched controls. This suggests a role for post-streptococcal autoimmune factors in a large proportion of cases. A larger odds ratio (12.1) was demonstrated when subjects had multiple GABHS infections in the previous year, suggesting a dose-dependent effect of exposure to infection. However, prospective longitudinal studies have failed to provide evidence that newly acquired GABHS infections precede tic exacerbations. The relative prevalence of PANDAS cases and the importance of autoimmune mechanisms to TS are controversial.

Clinical Findings

Signs & Symptoms

Tics are sudden, repetitive movements, gestures, or utterances that typically mimic an aspect of normal behavior. Individual tics rarely last more than a second. Many tics occur in bouts with brief inter-tic intervals of less than one second. Individual tics can occur singly or together in an orchestrated pattern. They vary in intensity or forcefulness. Motor tics, which can be viewed as disinhibited fragments of normal movement, can vary from simple, abrupt movements such as eye blinking, nose twitching, head or arm jerking, or shoulder shrugging to more complex movements that appear to have a purpose, such as facial or hand gestures or sustained looks. These two phenotypic extremes of motor tics are classified as simple and complex motor tics respectively. Similarly, phonic tics can be classified into simple and complex. Simple vocal tics are sudden, meaningless sounds such as throat clearing, coughing, sniffing, spitting, or grunting. Complex phonic tics are more protracted, meaningful utterances, which vary from prolonged throat clearing to syllables, words or phrases and to even more complex behaviors such as repeating ones own words (palalalia) or those of others (echolalia) and, in rare cases, the use of obscenities (coprolalia).

The severity of tics in TS waxes and wanes throughout the course of the disorder. The tics of TS and other tic disorders are highly variable from minute-to-minute, hour-to-hour, day-to-day, week-to-week, month-to-month, and even year-to-year. Tic episodes occur in bouts, which in turn also tend to cluster. Tic symptoms, however, can be exacerbated by stress, fatigue, extremes of temperature and external stimuli (e.g., in echolalia). Intentional movement attenuates tics in the affected area and intense involvement in activities tends to dissipate tic symptoms.

Many individuals with tics, especially those post-pubertal, are aware of premonitory urges: feelings of tightness, tension, or itching that are accompanied by a mounting sense of discomfort or anxiety relieved only by the performance of a tic. Premonitory urges are similar to the sensation preceding a sneeze or an itch. Premonitory urges cause many TS patients to suffer from an endless cycle of rising tension and tic performance because the relief provided by tic performance is ephemeral. Thus, soon after tic performance the tension of the premonitory urge again rises to a crescendo. A majority of patients also report a fleeting sense of relief after a bout of tics has occurred. Most are able to suppress their tics for short intervals of time.

With increasing awareness of premonitory urges, TS patients begin to exhibit a variable degree of voluntary control over tic performance. 92% of TS subjects in one study reported that the tics they exhibited were either partially or totally voluntary. However, this voluntary control should be likened to that governing eye blinking. Eye blinking and tics can both be inhibited voluntarily, but only for a limited period of time and only with mounting discomfort. Thus, some adult TS patients are able to demonstrate nearly complete control over when their tics will occur. However, when complete or near complete control of tics is present, resistance to the mounting tension of premonitory urges can produce mental and physical exhaustion even more distracting than the tics themselves.

The tics, which are the most prominent feature of TS, may be neither the first nor the most impairing psychological disturbance TS patients endure. Children with TS have higher rates of OCD, ADHD, and disinhibited speech and behavior compared to the general population. In one study, 65% of TS patients in late adolescence regarded their behavioral problems (including ADHD and OCD) and learning difficulties to have had an equal or greater impact on their life function than the tics themselves did. In the natural course of comorbid psychiatric illness in TS, ADHD symptom, typically precede the onset of tic symptoms by a couple of years, whereas OCD symptoms typically present around the age of 12–13 after tics have reached their peak severity. Approximately 50% of children with TS experience comorbid ADHD, and an even greater proportion of children with comorbid disorders reach clinical attention. Roughly one-third to one-half of TS patients will experience clinically significant OCD symptoms during the course of their lifetime. Figure 44–1 depicts the clinical course of comorbid ADHD and OCD symptoms in children with tic disorders.

Instruments for Diagnosis and Measurement

Direct observational methods (e.g., videotaped tic–counting) are the most objective measures of tic severity. However, the frequency of tics varies dramatically according to setting and activity. In addition, many individuals with TS can suppress their symptoms for brief periods of time. Thus, clinical rating scales are the preferred method for assessing initial tic severity and measuring change in tic severity. The Yale Global Tic Severity Scale is a clinician-rated, semi-structured scale that begins with a systematic inventory of tic symptoms rated as present or absent over the past week. Current motor and phonic tics are then rated separately according to number, frequency, intensity, complexity, and interference, in accordance with 6-point ordinal scales (0 = absent; 1 through 5 for severity). Three scores are yielded: Total Motor, Total Phonic and Total Tic. Self-report inventories such as the Yale Child Study Center TS Obsessive–Compulsive Disorder Symptom Questionnaire can be completed by the family prior to their initial consultation. They are valuable ancillary tools in order to gain a long−term perspective of the child's developmental course and the natural history of the tic disorder. The Yale Global Tic Severity Scale and Yale Child Study Center TS Obsessive–Compulsive Disorder Symptom Questionnaire are freely available.

Laboratory Findings and Imaging

At present, no laboratory testing or neuroimaging is useful in diagnosing or treating tic disorders. However, strong evidence from neuroimaging, neuropathological and neurochemical studies implicates abnormalities in the basal ganglia and CSTC circuits in the pathogenesis of TS. On volumetric MRI, individuals with TS have smaller caudate volume than healthy controls. Reduced caudate volume in children with TS has been associated with increased tic and OCD severity in adulthood. Functional neuroimaging has revealed increased activation of the frontal cortex and caudate during willful tic suppression. This increased activation of frontal cortex and caudate is in turn correlated with decreased activity of the globus pallidus, putamen, and thalamus. Positron emission tomography studies in TS have demonstrated increased striatal dopamine receptor and transporter densities and increased amphetamine induced dopamine release in the putamen.

Differential Diagnosis

Tic disorders must be distinguished from movement disorders caused by general medical conditions (e.g., Huntington's disease, stroke, Lesch-Nyhan syndrome, Wilson's disease, Sydenham's chorea, multiple sclerosis, postviral encephalitis, head injury) or the direct effects of a drug (e.g. akathisia and tardive dyskinesia associated with neuroleptic medication). Table 44–1 defines the major types of movements that commonly need to be distinguished from tics. Medical and family history, movement morphology, rhythm, and modifying influences are usually sufficient for making the diagnosis. Onset of movements prior to age 18, a waxing-and-waning course of symptoms and the changing of the specific tic movements over time are characteristic of TS.

In children, tics need to be distinguished from the stereotypies of stereotyped movement disorders or pervasive developmental disorder. Stereotypies typically have an earlier age of onset than tics, are bilateral rather than unilateral, and have a soothing quality. Table 44–2 contrasts tics and stereotypies. Complex tics need to be distinguished from the compulsions of OCD. Making this particularly difficult is the high comorbidity between the two conditions. Compulsions are usually performed in response to an obsession and preceded by anxiety, worry, or concern, whereas tics are generally performed in response to a physical sensation or urges. Compulsions typically are more elaborate than tics and are more likely to resemble “normal” behavior. Often a diagnosis of both OCD and tic disorder are warranted in the same individual.

Treatment

Given the usual waxing and waning course of tic disorders, it is probable that any intervention performed in response to symptom exacerbation will lead to clinical improvement. It is usually thus most prudent to treat overall, long-term symptom severity rather than chasing individual ebbs and flows in the natural course of the illness. Interventions should be started with the goal of reducing tics (and the side effects of treatment) to a level that minimizes social and educational impairment rather than to eliminate the tics completely (which will be unsuccessful in the majority of cases). Many cases of TS can be successfully managed without medication. When patients present with coexisting ADHD, OCD, depression, or bipolar illness it is usually better to treat these “comorbid” conditions first, as their successful treatment will often diminish tic severity.

Usual clinical practice focuses initially on educational and supportive intervention. Pharmacological treatments are typically held in reserve. The decision to employ psychoactive medication is usually made if the educational and supportive interventions have been in place for a period of months and it is clear that the tic symptoms are persistently severe and a source of impairment in terms of self-esteem, relationships with family or peers, or the child's school performance.

Psychoeducational Interventions

Educating the patient, his family members, teachers, and peers is among the most important interventions available. It should be undertaken for nearly all patients with tic disorders. Family psychoeducation should focus on the following:

1. Tics are not voluntary or provocative. They typically occur in “bouts” during which tics appear in rapid succession followed by tic-free intervals.

2. Physical sensations like an itch or before a sneeze are experienced by many patients prior to tics. TS is a sensorimotor disorder. A momentary sense of relief follows the tic.

3. Many patients are able to suppress tics over the short term but often at the expense of increasing discomfort and distraction due to the premonitory urges. It is not uncommon for a child to have relatively minor tics at school and then to let loose a bout of tics after coming home.

4. Tics increase and decrease in severity over time. Due to the natural ebb and flow of symptoms, any interventions started during an exacerbation of tic severity may appear successful, because of a natural decline in symptom severity.

5. Symptoms usually improve by adulthood. This information contradicts impressions gained from the lay literature that typically focuses on the most extreme cases.

6. Tics tend to be exacerbated by fatigue, sleeplessness, stress, excitement, changes in temperature, and streptococcal infection. Tics often tend to be alleviated when a child is deeply engaged in a motor activity such as sports, playing musical instruments, or dancing. The exact exacerbating and alleviating factors are highly individualized. Good sleep and regular exercise improve tics.

7. Comorbid ADHD, OCD, learning disabilities, and disruptive or disinhibited behaviors may occur. Improving these disorders often leads to an improvement in the tics.

Resources to help educate parents about tic disorders are available at the Tourette Syndrome Association website: www.tsa-usa.org

Perhaps equally important is educating the school. By educating the educators, clinicians can promote a positive and supportive environment in the classroom. If possible, teachers should respond to outbursts of tics with grace and understanding. Repeated scolding is counterproductive. The child may develop opposition to authority figures and be reluctant to attend school. Moreover, classmates may feel free to tease the child. A useful compendium of educational accommodations is available at http://www.tourettesyndrome.net/education.htm

Educating peers may be equally important. Many clinicians actively encourage patients, families, and teachers to educate peers and classmates about TS. It is remarkable what can be tolerated in the classroom and on the playground when teachers and peers simply know what the problem is and learn to disregard it.

Psychopharmacologic Intervention

Table 44–3 depicts the attributes of medications regularly used to treat tic disorder. Dopamine D2 receptor antagonists are the most predictably effective tic-suppressing agents over the short-term. Among the typical neuroleptics, haloperidol and pimozide have the most favorable data demonstrating efficacy. Long-term experience has been less favorable, and the “reflexive” use of these agents should be avoided. Common potential side effects are tardive dyskinesia, acute dystonia, sedation, depression, school and social phobia, and/or weight gain. In many instances, by starting at low dose and adjusting the dosage upwards slowly, clinicians can avoid these side effects. The goal should be to use as little medication as possible to render the tics “tolerable.” Attempts to stop the tics completely often risk over-medication.

Due to the extrapyramidal side effects associated with typical neuroleptics, atypical neuroleptics, such as risperidone, olanzapine and ziprasidone are now the most widely used medications to treat tic symptoms. These agents have potent 5-HT2 blocking effects as well as more modest blocking effects on dopamine D2. Double-blind clinical trials have supported the efficacy of risperidone, olanzapine, and ziprasidone. Risperidone and olanzapine are often associated with weight gain and sedation. Ziprasidone use can be associated with QT prolongation in children, so serial monitoring with electrocardiograms may be necessary.

Clonidine and guanfacine are potent α2-receptor agonists that are thought to reduce central noradrenergic activity. Although less effective in relieving tics compared to the neuroleptic medication, α2-receptor agonists have the advantage of also improving comorbid ADHD symptoms in patients with tics. The principal side effect associated with clonidine is sedation, which occurs in 10–20% of subjects. It abates with continued use. Other side effects include dry mouth, transient hypotension, and rare episodes of worsening behavior. To reduce the likelihood of symptom or blood pressure rebound, clonidine should be tapered and not withdrawn abruptly. Guanfacine is generally preferred to clonidine because it is less sedating and not associated with rebound hypertension following withdrawal. In extreme cases, botulinum toxin injections temporarily weaken muscles associated with severe motor or vocal tics. The most common sites of injection are the neck (for motor tics) and shoulders and throat (for vocal tics).

When comorbid ADHD is the most impairing to a patient presenting with comorbid tics, the stimulants methylphenidate, d-amphetamine, and Adderall are still first line agents for the medical management of ADHD. While most patients with both ADHD and a preexisting tic disorder do well on stimulants, clinical case reports and controlled studies indicate that some children with ADHD may exhibit tics de novo or experience a worsening of tics when exposed to a stimulant. Based on a large multisite randomized, controlled clinical trial, the combination of clonidine and methylphenidate is efficacious. Nonstimulants used in ADHD include atomoxetine, tricyclic antidepressants (desipramine and nortriptyline), atypical antidepressants such as bupropion, clonidine, and guanfacine.

Psychotherapeutic Interventions

Habit reversal training (HRT) is the first psychotherapeutic intervention that has shown promise in reducing tic severity in patients with TS. HRT significantly reduces tic symptoms in adults with TS when compared to supportive therapy in randomized, unblinded, wait-list controlled clinical trials. HRT has shown promise in uncontrolled trials among children with TS.

HRT consists of two main components: (1) awareness training and (2) competing response practice. Awareness training consists of 4 components designed to increase an individual's awareness of his own tics. These components include (1) response description—in which the patient learns how to describe tic movements and re-enacts them into a mirror; (2) response detection—in which the therapist aids the patient in tic detection by pointing out each tic immediately after it occurs in the session; (3) early warning procedure—in which an individual learns how to identify the earliest signs of tic occurrence; and (4) situational awareness training—in which an analysis is conducted to identify the high-risk situations when tics are most likely to occur. Competing response practice involves teaching individuals to produce an incompatible physical response (i.e., isometric contraction of tic-opposing muscles) upon the urge to perform a tic.

Neurosurgical Interventions

Neurosurgical interventions for TS are reserved for adults with intractable tics that severely affect social functioning. Originally, neurosurgical lesioning procedures were attempted to treat the most severe cases of TS. Deep brain stimulation, a relatively reversible, stereotactic technique, used to treat other movement disorders, has become the preferred method of neurosurgical treatment for medically intractable tics. Deep brain stimulation has several advantages over previous neurosurgical lesioning procedures in that it lacks many of the permanent complications typically associated with lesioning procedures (the electrodes can be removed), lends access to many surgically inaccessible sites, and allows for bilateral stimulation. It holds great promise for adult patients with intractable tics. However, in using Deep brain stimulation for tics, neither the appropriate site of electrode placement nor the electrode stimulation parameters have been established in carefully controlled clinical studies. The preferred sites of electrode placement are either the midline thalamic nuclei or the globus pallidus, pars internus (GPi). Case reports indicate a 50–80% improvement in tic frequency following the procedure. Every possible medical option to treat tics beforehand should be exhausted.

Prognosis

The onset of TS is usually characterized by simple, transient motor tics that affect the face (typically eye blinking) around 5–7 years of age. Over time, simple motor tics generally progress in a rostrocaudal direction affecting other areas of the face, followed by the head, neck, arms, and lastly and less frequently, the lower extremities. With time, vocal tics often appear, tics become increasingly complex, and premonitory urges are experienced. TS symptoms generally peak in severity between the ages of ten and twelve. Tic severity, however, typically dissipates with the onset of adolescence. The reduction in TS severity generally ends by the early twenties. Although a small minority of TS patients experience catastrophic outcomes in adulthood, on the whole, individuals rarely experience either a sustained worsening or improvement of their symptoms after the third decade of life. One-half to two-thirds of individuals with TS experience a marked reduction of symptoms by late adolescence and early twenties, and one-third to one-half of these patients become virtually asymptomatic in adulthood. Figure 44–2 diagrams the general course of tic severity of TS patients through the first two decades of their illness.

Given that tics in children are often ephemeral, producing substantial social and educational impairment when the tics are at their worst but little afterwards, the importance of minimizing social consequences (peer teasing, poor self-esteem, and social withdrawal) and educational impairment can not be overstated in determining long-term outcome. The proper management of, and vigilance for, psychiatric conditions highly comorbid with tic disorder, such as ADHD and OCD (that currently are more effectively treated) are also crucial. Ensuring that patients with a history of tic disorders refrain from using substances known to induce tics such as amphetamines or crack/cocaine is also likely to improve their prognosis.

Essentials of Diagnosis

DSM-IV-TR Diagnostic Criteria

Obsessive–Compulsive Disorder

1. Either obsessions or compulsions:

   • Obsessions as defined by (1), (2), (3), and (4):

     1. recurrent and persistent thoughts, impulses, or images that are experienced, at some time during the disturbance, as intrusive and inappropriate and that cause marked anxiety or distress

     2. the thoughts, impulses, or images are not simply excessive worries about real-life problems

     3. the person attempts to ignore or suppress such thoughts, impulses, or images, or to neutralize them with some other thought or action

     4. the person recognizes that the obsessional thoughts, impulses, or images are a product of his or her own mind (not imposed from without as in thought insertion)

   • Compulsions as defined by (1) and (2):

     1. repetitive behaviors (e.g., hand washing, ordering, checking) or mental acts (e.g., praying, counting, repeating words silently) that the person feels driven to perform in response to an obsession, or according to rules that must be applied rigidly

     2. the behaviors or mental acts are aimed at preventing or reducing distress or preventing some dreaded event or situation; however, these behaviors or mental acts either are not connected in a realistic way with what they are designed to neutralize or prevent or are clearly excessive

2. At some point during the course of the disorder, the person has recognized that the obsessions or compulsions are excessive or unreasonable.

3. The obsessions or compulsions cause marked distress, are time consuming (take more than 1 hour a day), and significantly interfere with normal routine, occupational (or academic) functioning, or usual social activities or relationships.

4. If another Axis I disorder is present, the content of the obsessions or compulsions is not restricted to it (e.g., preoccupation with food in the presence of an Eating Disorder; hair pulling in the presence of Trichotillomania; concern with appearance in the presence of Body Dysmorphic Disorder; preoccupation with drugs in the presence of a Substance Use Disorder; preoccupation with having a serious illness in the presence of Hypochondrias; preoccupation with sexual urges or fantasies in the presence of a Paraphilia; or guilty ruminations in the presence of Major Depressive Disorder).

5. The disturbance is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition.

(Reprinted, with permission, from Diagnostic and Statistical Manual of Mental Disorders, 4th edn., Text Revision. Copyright 2000 American Psychiatric Association.)

• In the above-mentioned listing, item B does not apply to children.
• A child must have either obsessions or compulsions, but not necessarily both, to qualify for a diagnosis of OCD. Obsessions are persistent ideas, thoughts, impulses, or images, experienced as intrusive and inappropriate, that cause marked anxiety or distress. Compulsions are repetitive behaviors (e.g., hand washing, checking) or mental acts (e.g., counting, repeating words silently) the goal of which is to prevent or reduce anxiety or distress, not to provide pleasure or gratification. Obsessions or compulsions must be severe enough to cause significant distress or impairment or take up more than 1 hour a day. It is not uncommon for children, especially younger children, with OCD to have clinically significant compulsions without the insight or ability to describe obsessions. This condition is known as “OCD with poor insight.”

General Considerations

Epidemiology

Results from the Epidemiological Catchment Area study of over 18,500 adults using structured clinical interviews estimated the lifetime prevalence of OCD among adults as 1.9–3.3%. Epidemiological studies of adolescents provide similar estimates, in the range of 1.9–3.6%. The sex distribution of these epidemiologic studies suggests that OCD affects males and females equally after puberty. However, males typically have an earlier age of onset, their first presentation occurring well before puberty.

Etiology

Abnormalities in the serotonin system appear to be central to the pathogenesis of OCD. Evidence favoring the serotonin hypothesis for OCD comes from the fact that serotonin reuptake inhibitors (SSRIs) such as fluoxetine, fluvoxamine, sertraline, and paroxetine are the most effective medications for OCD. The relative effectiveness of clomipramine, a serotonin selective tricyclic antidepressant strengthens this hypothesis. Exacerbation of OCD symptoms with the administration of mCPP, a serotonin agonist lends further support. High platelet serotonin levels and high cerebrospinal fluid concentration of 5-hydroxyindoline acetic acid (a major metabolite of serotonin) are correlated with treatment response to clomipramine in children with OCD. Evidence for the presence of abnormalities in other neurotransmitter systems, specifically dopamine, is evidenced by the successful augmentation of SSRI pharmacotherapy by neuroleptic medication and the high comorbidity of childhood OCD with tic disorders.

Consistent with the serotonin hypothesis, basal ganglia–frontal lobe dysfunction has been implicated in the pathogenesis of OCD. Positron emission tomography with the glucose analog [18F]fluorodeoxyglucose studies in children and adults with OCD demonstrate hypermetabolism in the caudate, orbitofrontal and anterior cingulate regions compared to normal controls during resting conditions and during periods of symptom provocation. These metabolic abnormalities were reversed with successful treatment, either behavioral or pharmacological. The high comorbidity of OCD with basal ganglia disorders such as TS and Sydenham's chorea supports this theory.

The association of obsessive-compulsive symptoms in Sydenham's chorea patients points to the importance of autoimmune processes in the pathogenesis of OCD. This observation led to the finding of a small subgroup of children with OCD or tic disorder who have pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). PANDAS cases have an abrupt, prepubertal onset of clinical symptoms (tic, OCD or both) after infection with GABHS. They experience symptom exacerbation with GABHS reinfection. PANDAS cases typically have a dramatic, episodic course and usually display coexisting choreiform movements if there are exacerbations. However, the prevalence of PANDAS remains controversial. PANDAS and OCD may be relatively infrequent. Nonetheless, the observation of OCD symptoms in Sydenham's chorea and the characterization of the PANDAS cohort of OCD and tic patients suggests the relevance of autoimmune and infectious factors to OCD pathogenesis.

Genetic and Environmental Factors

OCD contains a hereditable component. The strongest evidence supporting its hereditability comes from family studies and twins studies. Four family studies, each examining between 300 and 500 first-degree relatives of OCD patients, have estimated the rate of OCD to be 5–10-fold greater in first-degree relatives of OCD patients compared to the relatives of psychiatrically healthy controls. Twin studies in OCD have suggested an 87% concordance rate among monozygotic twins compared to 47% for dizygotic twins.

There is considerable evidence that TS and OCD share heritability, in other words that the same genes contribute to the phenotypic expression of both conditions. Relatives of OCD patients (without comorbid tics) have elevated rates of tic disorder compared to controls. Relatives of TS patients (irrespective of comorbid OCD diagnosis) have significantly higher rates of OCD than relatives of normal controls. An early age of onset (<18 years) is another factor associated with increased familial risk.

Studies examining potential genetic mechanisms have yet to identify unequivocally paraticular genes involved in the phenotypic expression of OCD. Among the most promising candidate genes are the serotonin transporter (SLC6A4) on 17q11 and the high-affinity neuronal excitatory amino acid transporter (SLAC1A1/ECCA-1) on 9p24.

Genetic studies of OCD have been hampered by the fact that OCD has a large degree of phenotypic heterogeneity and by a current lack of understanding into the molecular mechanisms underlying the disorder. The identification of quantitative endophenotypes with clinical, neuropsychological, imaging or electrophysiological measures, may advance the field.

With the exception of the PANDAS hypothesis, systematic efforts to identify environmental risk factors associated with OCD have lagged behind genetic studies. Current speculation focuses on perinatal adversity, parental child-rearing patterns, psychosocial stress (particularly the loss or threatened loss of close family members), traumatic brain injury, and exposure to drugs of abuse.

Clinical Findings

Signs and Symptoms

OCD is characterized by obsessions (unwanted and intrusive thoughts, images or impulses) and/or compulsions (repetitative behavioral or mental rituals). Since obsessions and compulsions are usually recognized by the child as nonsensical, inappropriate, or unreasonable, they are often both kept hidden from both parents and therapists. Especially in younger children, parental observation of compulsive behaviors (i.e., repeated checking of locks, washing or cleaning objects, hoarding) or physical signs of compulsive behavior (i.e., chapped hands or ulcerations from excessive washing,) can be the only definite signs of the disorder. Since the vast majority of OCD patients have insight into their condition, a detailed clinical history of obsessive and compulsive behavior from child and parents is sufficient to make a diagnosis of OCD. In order to qualify for a diagnosis of OCD, obsessions and compulsions must last more than 1 hour a day, and cause both distress and impairment.

OCD is generally considered to have a bimodal distribution in age of onset. One peak of incidence occurs in the peripubetal years and the other in early adulthood. Across the life cycle, the symptoms of OCD are similar. However, there are several important differences between pediatric and adult-onset OCD. Pediatric-onset OCD has a male predominance (unlike adult-onset OCD cases which are female-predominant), a stronger family history of OCD, and higher rates of comorbid ADHD and tic disorders. The specific content of obsessions and compulsions of OCD differ across age ranges. Children with OCD have much higher rates of aggressive obsessions (such as fear of a catastrophic event, fear of harm to self or others) and have poorer insight (i.e., being unable to recognize their obsessions and compulsions as excessive and unreasonable). Adolescents with OCD have a higher proportion of obsessions with sexual and religious themes, and cleaning and contamination-related symptoms are quite prevalent across age ranges. Patients with OCD and comorbid tics have a significantly higher rate of intrusive violent or aggressive thoughts and images, sexual and religious preoccupations, concerns with symmetry and exactness, hoarding and counting rituals, and touching and tapping compulsions compared to patients with non-tic OCD, who often suffer primarily from contamination worries and cleaning compulsions. Compulsions designed to eliminate a perceptually tinged mental feeling of unease, coined in the literature as “just right” perceptions, are particularly typical of patients with OCD and comorbid tics.

There is a very high prevalence of comorbid psychiatric illness in children with OCD. In clinical samples, around 80% of children with OCD had comorbid illness. Tic disorders, ADHD, and anxiety disorder such as separation anxiety disorder are particularly common among children receiving treatment for OCD, whereas depression and anxiety disorders are particularly common in adolescent patients. Each of these comorbidities affects one-fifth to one-third of OCD patients reaching clinical attention. Proper screening for comorbid illness of OCD patients as well as the specific content and character of each patient's individual OCD symptoms is crucial to developing a proper pharmacological and behavioral treatment strategy. Comorbid psychiatric illnesses and comorbid tic disorders are associated with poor long-term outcome in children with OCD. Furthermore, OCD patients with comorbid tics have a poorer response to SSRI pharmacotherapy but an increased likelihood of responding to antipsychotic augmentation.

Instruments for Diagnosis and Measurement

The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is the standard clinical rating scale for the assessment of symptom severity in adults with OCD. The Y-BOCS is a 10-item ordinal scale (0–4) that rates the severity for both obsessions and compulsions according to time occupied, degree of interference, subjective distress, internal resistance, and degree of control. The Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) is a similar scale for use with children with OCD. CY-BOCS and Y-BOCS scales differ only according to the accompanying symptom screening checklist, the CY-BOCS being more developmentally appropriate. Both scales have been validated for use in their representative patient populations and are sensitive to changes in symptom severity following treatment. Both scales rate OCD symptoms from 0 (no symptoms) to 40 (severe OCD), a score less than 8 being considered as subclinical, over 16 as clinically significant, and over 24 as moderate to severe. Generally, a reduction in the Y-BOCS score of 25–35% with a final Y-BOCS rating of less than 16 is considered the criterion for response to treatment. The Y-BOCS rating scale takes approximately 5 minutes to complete once the patient has completed the initial symptom checklist. It serves as a good measure of symptom fluctuation in a clinical setting.

As OCD seems to be heterogeneous, with multiple genetic and environmental influences, researchers have stressed the importance of characterizing the differences between types of OCD patients so as to create more homogenous populations for genetic and neuroimaging studies. With this aim, the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS) was created. The DY-BOCS uses a combination of self-report checklists and clinician ratings to assess the presence and severity of OCD symptoms in 6 thematically related symptom dimensions: aggression/harm, cleaning/contamination, symmetry/ordering, religious/sexual, hoarding, and miscellaneous. The DY-BOCS rates symptom severity according to time occupied, subjective distress, and the interference that obsessions and compulsions cause within these 6 domains.

Laboratory Findings and Imaging

At present, no laboratory or neuroimaging findings are useful in either making the diagnosis of OCD or in predicting its prognosis or treatment. Clinical findings are sufficient. However, neuroimaging studies of OCD patients support the hypothesis that orbitofrontal–subcortical dysfunction is central to pathogenesis. PET symptom provocation studies have demonstrated hypermetabolism in the anterior-lateral orbitofrontal cortex, caudate nucleus and paralimbic brain areas of OCD patients when they are exposed to situations that provoke OCD symptoms compared to neutral stimulus periods. PET studies have also implicated hypermetabolism in the orbitofrontal cortex and caudate nucleus in subjects with OCD compared to normal controls. Hypermetabolism in these areas reverses with successful pharmacotherapy with SSRIs or cognitive behavioral therapy. Structural volumetric MRI studies of adult subjects with OCD find increased left gray orbitofrontal volumes and reduced overall orbitofrontal volumes compared to normal controls. MRI studies examining psychotropic-naïve children with OCD find increased anterior cingulate gray matter volume, increased globus pallidus volume, and reduced striatal volume compared to normal controls.

Differential Diagnosis

Recurrent thoughts, images and impulses similar to the obsessions present in OCD are encountered in many other mental disorders. For instance, in Major Depressive Episodes it is not uncommon for patients to have persistent thoughts about unpleasant circumstances, personal worthlessness, or possible alternative actions. These ruminative thoughts can be distinguished from those of OCD by the fact that they are mood-congruent and ego-syntonic compared to the obsessions of OCD. There is a high comorbidity between depression and OCD; thus it is common for both ruminative depressive thoughts and obsessive thoughts to present in the same individual. The symptoms of other anxiety disorders can also mimic the symptoms of OCD. Generalized Anxiety Disorder is characterized by excessive worry, but worries can be distinguished from obsessions by the fact that the person experiences them as excessive concern about real-life circumstances, whereas obsessions are generally experienced as excessive but unreasonable. The obsessions of OCD must also be distinguished from excessive worries in mental disorders about appearance (body dysmorphic disorder, anorexia and bulimia), a specific situation or circumstance (specific phobia), or serious illness due to misinterpretation of normal bodily signals (hypochondria).

In children, OCD obsessions concerning the fear of harm to self or others must be distinguished from the fears typical of separation anxiety disorder. These two conditions can be distinguished by the observation that the obsessions of OCD are usually accompanied by stereotyped and specific compulsive rituals (i.e., checking behavior, counting), whereas in separation anxiety disorder the compulsive actions are less stereotyped. Furthermore, the occurence of other OCD symptoms besides fear of harm aids in diagnostic clarification.

The repetitive stereotypies of children with autism spectrum disorders, mental retardation and pervasive developmental disorders can resemble the compulsions of OCD. However, stereotypies can usually be easily distinguished from the obsessions of OCD because of the child's accompanying symptoms and the fact that stereotypies are usually experienced as soothing or pleasurable whereas compulsions are ego-dystonic. Stereotypies can be present in children with normal socialization skills, cognitive ability and developmental trajectory. In these cases an early onset of symptoms (less than 2 years of age) and an increase in stereotypies with excitement can be used to distinguish the two conditions. Complex tics in children with TS can mimic the compulsions of OCD. Complex tics are usually preceded by a premonitory urge, whereas compulsions are preceded by anxiety or a specific obsession. The high comorbidity between tic disorders and OCD can make this distinction difficult.

Treatment

Cognitive–Behavioral Therapy (CBT) and pharmacotherapy are effective therapies in the treatment of pediatric OCD. In one double-blind, multi-center, placebo-controlled study, the combination of CBT and Zoloft has been demonstrated to be superior to either CBT or pharmacotherapy alone. All children with OCD should be offered CBT unless there is a strong clinical reason not to do so.

Psychotheraputic Interventions

Cognitive behavioral therapy for children with OCD is based on exposure and response prevention. With a number needed to treat of 2.6 (95% CI: 1.7–4.2) to induce a treatment-response in children with OCD, CBT is a first-line treatment for OCD across all age ranges. In CBT for OCD, the therapist must first examine and take a detailed history of a child's specific OCD symptoms. Symptom checklists such as those that accompany the CY-BOCS and Y-BOCS rating scales are useful. The therapist, working with child and parent, designs a hierarchy of exposures, both direct and imaginary, aimed to trigger the anxiety associated with the obsessions of OCD (e.g., touching a toilet seat for a child with contamination concerns, imagining a parent in a car accident for a child with fears of harm coming to others). The therapist then enters into a contract with the child and parent to work on completing the exposures over a set time frame, usually a couple of months. Next, the therapist engages in the specific exposures with the child (and sometimes parent) over several treatment sessions. The child agrees not to engage in his compulsions in response to the anxiety produced. During exposures the child reports on his level of anxiety using subjective units of distress (an anxiety thermometer). Child and parent are given similar exposure assignments to complete after each session. With increased duration of exposure and with further exposures (without performing the compulsions), the child's anxiety lessens, helping him to overcome the OCD. Most CBT treatment manuals for children with OCD are freely available. They include techniques for helping children deal with stress and anxiety such as relaxation therapy. They may also include exercises to illustrate other tenets of CBT such as recognizing cognitive distortions common in OCD (e.g., overestimation of risk, all-or-nothing thinking, overcoming the need for certainty, and recognizing excessive feelings of responsibility or guilt). If a CBT therapist is not available, there are therapeutic manuals that have distilled these treatment methods in a form that can be learned by a clinician in a time-efficient manner. Moreover, self-help books are available to allow parents and children to engage in aspects of treatment themselves.

Psychopharmacologic Interventions

SSRIs and clomipramine are the first-line pharmacotherapy for both children and adults with OCD. Clomipramine, fluoxetine, fluvoxamine, paroxetine, sertraline and citalopram have demonstrated superior efficacy to placebo in randomized, double-blind, placebo-controlled clinical trials. Table 44–4 depicts the traditional starting and target doses for SSRIs across the age spectrum. The number of subjects needed to detect a reasonable clinical treatment response (defined by a 25–35% reduction in CY-BOCS scores) has ranged from 4 to 6 in double-blind, placebo-controlled studies. Based on cumulative studies, SSRI pharmacotherapy will lead to an average of a 6.5–9 point decline in CY-BOCS ratings and an average 30–38% reduction in symptom severity. In a meta-analysis of pharmacotherapy trials for pediatric OCD, based on meta-regression techniques, clomipramine was found superior to the SSRIs. The other SSRIs currently used to treat OCD were roughly equivalent. Clomipramine may be superior to other serotonergic agents due to its unique pharmacodynamic properties. Clomipramine is metabolized into desmethylclomipramine, a secondary amine tricyclic antidepressant identical to desipramine with a chloride atom substitution. Desipramine has been reported to be effective in treating TS and ADHD. Thus, clomipramine may be more effective in treating the disorders associated with OCD than traditional SSRIs are. These meta-regression results should be interpreted with caution. No studies have directly compared the efficacy of clomipramine to other SSRIs in children with OCD. Studies comparing these agents in adults have found no significant differences.

Despite modest evidence suggesting it might be more effective than SSRIs in children, clomipramine is rarely used as the initial pharmacological agent in OCD due to its side effect profile. In view of the potential arrythmogenic properties of clomipramine, a baseline electrocardiogram and a detailed screening for a personal and family history should be undertaken in all patients before the initiation of pharmacotherapy. The U. S. Food and Drug Administration guidelines for unacceptable EKG indices for use of clomipramine are as follows: (1) PR interval > 200 ms, (2) QRS interval > 30% increased over baseline or > 120 msec, (3) blood pressure greater than 140/90, (4) heart rate > 130 bpm, or (5) QTc > 450 msec. Moreover, clomipramine has a worse side effect profile than SSRIs, with high rates of somnolence, gastrointestinal upset, reduced seizure threshold, and anticholinergic side effects. Despite these concerns, clomipramine remains a valuable treatment for children who do not respond to one or more SSRIs.

SSRIs are the first line pharmacologic treatment for children with OCD. Based on the currently available clinical trials literature, there is no evidence that one SSRI is more effective than another. The starting and target doses for SSRIs in children are depicted in Table 44–4. Pharmacological treatment for patients with SSRIs should continue for 2–3 months at the maximal tolerated dose of medication before a child is considered a nonresponder. Many OCD patients respond only after many weeks of SSRI monotherapy.

Augmentation Strategies

Approximately half of children placed on SSRIs fail to respond despite appropriate medication. If CBT has not been conducted, it should be at this point. In adults with OCD, as many as 25% of nonresponders respond if treated with another SSRI or clomipramine. There is modest evidence that, in children with OCD, clomipramine is more effective than SSRI. Furthermore, augmentation with neuroleptic medication has been demonstrated to be an effective strategy in the treatment of adults with OCD. In adults with OCD, the number of subjects needed to detect a clinically significant treatment response (35% reduction in Y-BOCS ratings) was 4.5 (95% CI: 3.2–7.1). Neuroleptic augmentation is particularly effective in OCD patients suffering from comorbid tics (NNT = 2.3), a result that is not surprising since neuroleptic medication is the mainstay of tic treatment. The doses of neuroleptic medications used to augment SSRIs are much lower than those used to treat psychosis and aggression in children.

Prognosis

Results from the Pediatric OCD Treatment Study and similarly designed randomized, double-blind clinical trials of pharmacological and behavioral treatments for OCD indicate that approximately one-third to one-half of children with OCD will experience a treatment response after 12 weeks of either behavioral or pharmacological treatment for OCD. The likelihood of treatment response is significantly higher when combination therapy with both cognitive behavioral therapy and pharmacotherapy with an SSRI are initiated at the beginning of treatment. The ability of children with OCD to sustain improvement over the long-term with either of these two treatment modalities is less well studied.

A meta-analysis of long-term outcome in pediatric-onset OCD estimated that the persistence rate for full OCD was 41% and for full or subclinical OCD was 60% after 1–7 years of follow-up. Predictors of poor long-term outcome in this meta-analysis were early age of OCD onset, poor initial treatment response and comorbid psychiatric illness. The presence of a comorbid tic disorder has also been associated with poor outcome in prospective, long-term outcome studies.