Tourette syndrome and obsessive-compulsive disorder

Tourette syndrome and obsessive-compulsive disorder are neuropsychiatric disorders that have sparked considerable interest over the decades. They are the focus of research for a remarkable diversity of disciplines, ranging from neuroimagers and prenatal epidemiologists to experts in the neural circuits that connect the cortex with the basal ganglia, as well as neuroimmunologists focusing on brain-based autoimmune phenomena. Several hypotheses have been put forward to explain the onset and exacerbation of these illnesses. Here, we discuss the clinical phenomenology and treatment options that are currently available. New psychopharmacological agents are being used that are based on a greater understanding of the neurobiology and are being used in combination with behavioral interventions. Longitudinal clinical investigations into clinical symptoms and the natural course are providing additional clues on the underlying pathophysiology. Recent advances in research models are also reviewed in an attempt to clarify some of the molecular etiologies that lead to these disorders.     

Obsessive-compulsive disorder in Tourette syndrome

Several lines of evidence suggest a meaningful association between obsessive-compulsive disorder and Tourette syndrome, including comorbidity, phenomenologic overlap, evidence from family and genetic studies, and the possible role of basal ganglia circuitry in both conditions. Obsessive-compulsive behaviors occur frequently in patients who have Tourette syndrome and tend to have a later onset than tics. Despite commonalities, the approaches to treating tics and obsessive-compulsive symptoms are actually quite distinct. A specialized form of cognitive behavior therapy and pharmacotherapy with a potent serotonin reuptake inhibitor are the two established first-line therapies for obsessive-compulsive disorder. An adequate trial of a serotonin reuptake inhibitor is 10 to 12 weeks in duration at doses near the upper end of the recommended range for age and weight. Cases of obsessive-compulsive disorder that do not sufficiently improve with serotonin reuptake inhibitors might benefit from adjunctive low-dose antipsychotic (eg, risperidone) medication whether or not tics are present. Warnings about an increased risk of suicidality among children and adolescents taking antidepressants for pediatric depression extend to those taking the medications for obsessive-compulsive disorder, but the risk-to-benefit ratio is more favorable in this latter population because several serotonin reuptake inhibitors have been shown to be efficacious in obsessive-compulsive disorder.     

Anti-striatal antibodies in Tourette syndrome cause neuronal dysfunction

Serologic studies of children with Tourette syndrome (TS) have detected anti-neuronal antibodies but their role in TS has not been explored. Stereotypies and episodic utterances, analogous to involuntary movements seen in TS, were induced in rats by intrastriatal microinfusion of TS sera or gamma immunoglobulins (IgG) under noninflammatory conditions, as found in TS. Immunohistochemical analysis confirmed the presence of IgG selectively bound to striatal neurons. These data support the hypothesis that binding of an anti-neuronal antibody from some children with TS induced striatal dysfunction and suggest a possible cause for the basal ganglia alterations observed in children with TS.     

Examination of the SGCE gene in Tourette syndrome patients with obsessive-compulsive disorder.

Mutations in the epsilon-sarcoglycan gene (SGCE) have been reported in families with myoclonus-dystonia (M-D). In addition to abnormal movements, obsessive-compulsive disorder (OCD) has also been described in families with M-D. OCD is a common feature in another movement disorder, namely Tourette syndrome (TS). The comorbidity of these disorders suggests that common genetic factors might be involved in their susceptibility. To evaluate this, we performed two sets of experiments. An association study using a polymorphism within an intron of the SGCE gene was assessed in patients with TS and OCD versus controls, and the SGCE gene itself was screened for mutations in all TS/OCD patients, followed by direct sequencing of the gene in a limited number of these patients. No correlation was found by either method.     

Early-onset Tourette syndrome with reversible autistic behaviour: a dysmaturational disorder

Early-onset Tourette syndrome comorbid with reversible autistic behaviour is described in twelve young males. After a normal gestation, delivery and first-year development, regression set in between the age of one and two with loss of various abilities and the emergence of autistic behaviour. At this time, or slightly later, they showed multiple motor and vocal tics, simple and complex: the latter could also be traced to most of their parents. Following an intervention based on intense cuddling, motor activation and paedagogic guidance, these children's abilities rapidly improved, reaching at follow-up a normal or borderline intellectual functioning and with the disappearance of their initial autistic behaviour. At follow-up tics were present in all, usually with the features of a full-blown Tourette syndrome, often comorbid with ADHD, and in some cases with OCD. Accepted: 6 June 2001     

Decreased platelet imipramine binding in Tourette syndrome children with obsessive-compulsive disorder.

[3H]Imipramine binding to blood platelets was assessed in eight untreated Tourette syndrome (TS) children, nine drug-free TS children with obsessive-compulsive disorder (OCD), and nine age-matched and gender-matched control subjects. The density of [3H]imipramine binding sites in TS + OCD patients was significantly lower compared with TS-OCD patients (28%) as well as when compared with controls (31%). This alteration was not accompanied by differences in the affinity of the binding site to the ligand. The decreased density of the platelet serotonin "transporter" might implicate the involvement of the serotonergic system in the pathophysiology of OCD in TS patients, but not in TS per se.     

Malignant Tourette syndrome.

The aim of this work was to draw attention to potentially life-threatening symptoms associated with Tourette syndrome (TS) and to explore their relationship to TS comorbidities. Medical records of all patients with TS evaluated at our Movement Disorders Clinic between July 2003 and July 2006 were reviewed. Data on patients with malignant TS, defined as >or=2 emergency room (ER) visits or >or=1 hospitalizations for TS symptoms or its associated behavioral comorbidities, were entered into a dataset and analyzed. Five illustrative cases are described. Of 333 TS patients evaluated during the 3-year period, 17 (5.1%) met the criteria for malignant TS. Hospital admission or ER visits were for tic-related injuries, self-injurious behavior (SIB), uncontrollable violence and temper, and suicidal ideation/attempts. Compared with patients with nonmalignant TS, those with malignant TS were significantly more likely to have a personal history of obsessive compulsive behavior/disorder (OCB/OCD), complex phonic tics, coprolalia, copropraxia, SIB, mood disorder, suicidal ideation, and poor response to medications. Although TS is rarely a disabling disorder, about 5% of patients referred to a specialty clinic have life-threatening symptoms. Malignant TS is associated with greater severity of motor symptoms and the presence of >or=2 behavioral comorbidities. OCD/OCB in particular may play a central role in malignant TS; obsessive compulsive qualities were associated with life-threatening tics, SIB, and suicidal ideation. Malignant TS is more refractory to medical treatment than nonmalignant TS.     

Congenital spinal cord haemangioblastoma: another cause of spinal cord section syndrome in the newborn.

A newborn infant with negative perinatal history and characteristic clinical findings of upper cervical spinal cord section is described. Metrizamide myelography performed on the 7th and 22nd days of life was negative. Peroneal somatosensory evoked responses showed a conduction block at the cervical level. Necropsy revealed a haemangioblastoma extending from levels C1 to C5.     

Aggressive behaviour in children with Tourette syndrome and comorbid attention-deficit hyperactivity disorder and obsessive-compulsive disorder.

BACKGROUND: Aggressive behaviour, defined as sudden, explosive outbursts of rage, has been reported as a clinical problem in approximately 23% to 40% of Tourette syndrome (TS) patients (1-5). Attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) are also reported in 50% to 70% of TS patients (6). OBJECTIVE: To investigate whether aggressive behaviour was associated with TS directly or found primarily in TS with comorbid ADHD or OCD. METHOD: Aggressive behaviour in 33 nonmedicated patients with TS (ages 6 to 14 years) and 6 healthy control subjects (ages 7 to 12 years) was examined by semistructured interview and multiinformant questionnaires. RESULTS: Aggression subscales on Achenbach's Child Behavior Checklist (CBCL) completed by parents and Teacher's Report Form (TRF) completed by teachers distinguished the TS-only and control groups from the group with TS + Comorbidity (P < 0.046, and P < 0.016) after adjusting for tic severity and age. The conduct disorder subscale on the Conners Parent Rating Scale (CPRS) was also significantly higher (P < 0.005) in the TS + comorbidity group than in the TS-only or control groups, with more problems reported in the older children. CONCLUSIONS: These findings provide additional evidence that aggressive behaviour observed in children with TS may be associated with comorbid ADHD or OCD (6), independent of tic severity or age. This is consistent with the clinical observation that most TS patients have only minimal symptoms, which do not interfere with their daily functioning.     

Gilles de la Tourette syndrome and voluntary movement: a functional MRI study

Tourette syndrome (TS) is hypothesised to be caused by an abnormal organization of movement control. The aim of this study was to use functional magnetic resonance imaging to study motor cortex activation in a TS patient. Usual and unusual self-paced voluntary movements were performed. The TS patient displayed supplementary motor area (SMA) activation during both tasks. This activation reflects a continuous use of the SMA to perform the voluntary motor movements required in both tasks. Moreover, the absence of tics during the execution of these voluntary motor tasks suggests that tic activity may be suppressed by additional mental effort.     

Neurocognitive correlates of child obsessive compulsive disorder and Tourette syndrome

This study investigated the neurocognitive correlates of childhood OCD and TS, which are purported to share frontal-striatal dysfunction. Neurocognitive measures tapping frontal-striatal functions such as executive, attention/memory, and visuomotor abilities were administered to three groups of participants, OCD without comorbid TS (OCD), TS without comorbid OCD (TS), and normal controls. Results suggested that OCD group demonstrated deficits in the area of spatial attention relative to healthy controls. The OCD participants demonstrated no cognitive deficits compared to the TS group. TS participants showed trends towards impairments in the areas of response inhibition, divided attention, and cognitive flexibility relative to the OCD and normal control groups. Spatial attention deficits for the OCD group are partially consistent with adult OCD studies indicating deficits in spatial memory. TS findings were less robust and may be construed tentatively as suggestive of executive function deficits. Future research is needed to delineate the influence of development on neurocognitive deficits associated with OCD and TS.     

Chronic tics and Tourette syndrome in patients with obsessive-compulsive disorder

Tourette syndrome (TS) and chronic motor/vocal tics (CMVT) are both common disorders in patients with obsessive compulsive disorder (OCD). However, there have been few studies evaluating the differences between the OCD with TS and OCD with CMVT subgroups. This study was conducted in order to further investigate possible differences between the expression of the OCD phenotype in OCD with TS and that seen in OCD with CMVT. One hundred and fifty-nine outpatients referred to an OCD research program were evaluated using the following instruments: the Structured Clinical Interview for DSM-IV; the Yale-Brown Obsessive Compulsive Scale; the Yale Global Tic Severity Scale; and the USP-HARVARD Repetitive Behaviors Interview. Patients were divided into three groups: OCD patients without tics (OCD − TICS, n = 98), OCD patients with chronic motor or vocal tics (OCD + CMVT, n = 31) and OCD patients with TS (OCD + TS, n = 30). OCD + CMVT patients were similar to OCD + TS patients regarding the frequency of intrusive sounds, repeating behaviors, counting and tic-like compulsions (in both cases more frequent than in OCD − TICS patients). For age at obsessive-compulsive (OC) symptom onset, sensory phenomena score, number of comorbidities, frequency of somatic obsessions, bodily sensations and just-right perceptions, OCD + CMVT patients tended to be in between the other two groups. Our results suggest that there are qualitative and quantitative differences in the phenotypic expression of tic disorders in OCD patients, depending on whether the subject has TS or only CMVT.     

难治性抽动秽语综合征伴强迫症的立体定向手术治疗

目的 总结立体定向手术毁损一侧丘脑腹外侧核(VL)/板中间核(LM)联合未定带(ZI)和双侧扣带回前部(ACG)毁损治疗抽动秽语综合征(GTS)伴强迫症的经验.方法 术前录像记录患者平静下抽动情况.手术采用磁共振引导下立体定向射频毁损方式,一侧ZI+VL/LM毁损控制抽动症状,双侧AC毁损控制强迫症状.抽动严重程度以耶鲁大体抽动量表(YGTSS)评价,强迫行严重程度以耶鲁布朗强迫症量表(YBOCS)评价.结果 23例患者接受一侧ZI+VL/LM联合双侧ACG毁损术,其中左侧ZI+VL/LM毁损14例,右侧ZI+VL/LM 9例.术后患者肢体抽动较术前明显改善,其YGTSS评分由术前(20.3±7.2)分明显下降至术后(9.8±3.2)分(P<0.05);术后患者不自主发声显著缓解,其YGTSS评分由术前(19.6±8.8)分明显下降至术后(10.2±3.1)分(P<0.05);术后患者总体病情、生活质量显著提高,其YGTSS评分由术前(70.3±17.2)分明显下降至术后(30.8±10.9)分(P<0.05).另外,术后强迫症也明显缓解,其YBOCS评分由术前(37.2±3.9)分明显下降至术后(17.2±3.2)分(P<0.05).23例患者均未出现严重并发症.结论 一侧VL/LM联合ZI区和双侧ACG毁损术可有效地控制GTS,对GTS伴发的强迫症也有良好的疗效.     

Tourette syndrome: recent advances

Clinical and genetic studies have allowed the limits of Tourette syndrome to be broadened. There is now strong evidence that chronic motor tics and Tourette syndrome are different manifestations of an autosomal dominant gene with high penetrance. A genetic link with obsessive-compulsive disorder also appears to have been established. Up to 10% of cases of Tourette syndrome may be nongenetic phenocopies, however. There is also an association between Tourette syndrome and attention deficit hyperactivity disorder. This complicates therapy, as psychostimulant drugs may precipitate or exacerbate tics in some individuals. A high proportion of patients with Tourette syndrome also has neuropsychological deficits and learning disabilities. The pathophysiology is incompletely understood. The best supported hypothesis is that there is dopamine receptor supersensitivity, although there are strong suggestions of abnormalities in serotonin metabolism. The possibility of abnormalities in neuropeptide systems is being explored. Treatment of tics relies primarily on neuroleptics with dopamine receptor blocking activity. Clonidine may be useful in some patients, especially those with behavior problems. Obsessive-compulsive symptoms can be treated using appropriate pharmacologic agents. The treatment of attention deficit disorder in patients with tics should begin with behavioral strategies. Clonidine can be tried as the first-line drug, and psychostimulants should be used only if necessary and with great caution. In rare instances it may be necessary to combine a psychostimulant and a neuroleptic.     

Tourette syndrome: recent advances

In spite of new information relevant to the clinical and biological features of Tourette syndrome, areas of controversy still exist. A genetic substrate is present in at least some affected families; there also is clearly a genetic relationship between Tourette syndrome and chronic motor tic disorder. Patients with Tourette syndrome have an increased incidence of behavior problems, attention deficit disorder, and obsessive-compulsive symptoms. Treatment of the attention deficit disorder with psychostimulant drugs will exacerbate tics in some patients. Haloperidol remains the most consistently useful therapeutic agent. Pimozide and clonidine also may be useful, but further work is required before standard treatment protocols can be developed. The disorder most likely results from dysfunction of dopaminergic systems.