Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention deficit/hyperactivity disorders

BACKGROUND: Previous studies have provided preliminary serological evidence supporting the theory that symptoms of tic disorders or obsessive-compulsive disorder (OCD) may be sequelae of prior streptococcal infection. It is unclear, however, whether previously reported associations with streptococcal infection were obscured by the presence of diagnostic comorbidities. It is also unknown whether streptococcal infection is associated in vivo with anatomical alterations of the brain structures that have been implicated in the pathophysiology of these disorders. METHODS: Antistreptococcal antibody titers were measured in 105 people diagnosed as having CTD, OCD, or attention-deficit/hyperactivity disorder (ADHD) and in 37 community controls without a disorder. Subjects were unselected with regard to their history of streptococcal exposure. Basal ganglia volumes were measured in 113 of these subjects (79 patients and 34 controls). RESULTS: A DSM-IV diagnosis of ADHD was associated significantly with titers of 2 distinct antistreptococcal antibodies, antistreptolysin O and anti-deoxyribonuclease B. These associations remained significant after controlling for the effects of CTD and OCD comorbidity. No significant association was seen between antibody titers and a diagnosis of either CTD or OCD. When basal ganglia volumes were included in these analyses, the relationships between antibody titers and basal ganglia volumes were significantly different in OCD and ADHD subjects compared with other diagnostic groups. Higher antibody titers in these subjects were associated with larger volumes of the putamen and globus pallidus nuclei. CONCLUSIONS: These findings suggest that the prior reports of an association between antistreptococcal antibodies and either CTD or OCD may have been confounded by the presence of ADHD. They also support the hypothesis that in susceptible persons who have ADHD or OCD, chronic or recurrent streptococcal infections are associated with structural alterations in basal ganglia nuclei.     

Clinical phenomenology and phenotype variability in Tourette syndrome

Tourette syndrome (TS) is a neurodevelopmental disorder with a rich phenomenology that includes simple and complex motor and vocal tics as well as multiple comorbidities. From a nosological perspective, it is evident that a continuum of tic severity exists, of which TS is the most severe and rare form, while transient tics and chronic tics represent milder forms. From a psychopathology perspective, TS is often concurrent with obsessive–compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD); these disorders appear to define TS “types” TS only, TS+OCD, and TS+OCD+ADHD. Additional clinical aspects of TS include more frequent than expected occurrence of anger episodes, anxiety disorders, mood disorders, impulse control disorders, learning disorders, and pervasive developmental disorders. Data reduction techniques have been used more recently to define a “simple” and “complex” tic symptom clusters or factors. Phenomenologic approaches can be used in TS to guide future pathophysiologic research.     

Clinical phenomenology and phenotype variability in Tourette syndrome

Tourette syndrome (TS) is a neurodevelopmental disorder with a rich phenomenology that includes simple and complex motor and vocal tics as well as multiple comorbidities. From a nosological perspective, it is evident that a continuum of tic severity exists, of which TS is the most severe and rare form, while transient tics and chronic tics represent milder forms. From a psychopathology perspective, TS is often concurrent with obsessive–compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD); these disorders appear to define TS “types” TS only, TS+OCD, and TS+OCD+ADHD. Additional clinical aspects of TS include more frequent than expected occurrence of anger episodes, anxiety disorders, mood disorders, impulse control disorders, learning disorders, and pervasive developmental disorders. Data reduction techniques have been used more recently to define a “simple” and “complex” tic symptom clusters or factors. Phenomenologic approaches can be used in TS to guide future pathophysiologic research.     

ADHD prevalence and association with hoarding behaviors in childhood‐onset OCD

Background: It has been suggested that attention‐deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD), both neurodevelopmental disorders with onset in childhood, are highly comorbid, but previous studies examining ADHD and OCD comorbidity have been quite variable, partly because of inconsistency in excluding individuals with tic disorders. Similarly, ADHD has been postulated to be associated with hoarding although this potential relationship is largely methodologically unexplored. This study aimed to examine the prevalence of ADHD among individuals with childhood‐onset OCD but without comorbid tic disorders, as well as to examine the relationship between clinically significant hoarding behaviors (hoarding) and ADHD. Method: ADHD prevalence rates and the relationship between ADHD and hoarding were examined in 155 OCD‐affected individuals (114 probands and 41 relatives, age range 4–82 years) recruited for genetic studies and compared to pooled prevalence rates derived from previously published studies. Results: In total, 11.8% met criteria for definite ADHD, whereas an additional 8.6% had probable or definite ADHD (total=20.4%). In total, 41.9% of participants with ADHD also had hoarding compared to 29.2% of participants without ADHD. Hoarding was the only demographic or clinical variable independently associated with ADHD (odds ratio=9.54, P<0.0001). Conclusion: ADHD rates were elevated in this sample of individuals with childhood‐onset OCD compared to the general population rate of ADHD, and there was a strong association between ADHD and clinically significant hoarding behavior. This association is consistent with recent studies suggesting that individuals with hoarding may exhibit substantial executive functioning impairments and/or abnormalities, including attentional problems. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

The behavioral spectrum of tic disorders: a community-based study

BACKGROUND: Tourette syndrome (TS) and related tic disorders are commonly associated with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). It has been argued, however, that any observed association between TS and these and other psychopathologies may be due to ascertainment bias in that individuals with multiple problems are more likely to be referred for medical evaluation. METHODS: In order to overcome the potential confounding by ascertainment bias, the authors conducted a community-based study of school children using direct interviews to determine the prevalence of tic disorders and any comorbid psychopathology. A standard psychiatric interview and standardized rating scales were utilized to diagnose childhood behavioral disorders. RESULTS: Of the 1,596 children interviewed, 339 were identified as having tics. The following psychopathologies were found more commonly (p < 0.05) in the children with tics: OCD, ADHD, separation anxiety, overanxious disorder, simple phobia, social phobia, agoraphobia, mania, major depression, and oppositional defiant behavior. CONCLUSION: The behavioral spectrum of tic disorders includes OCD, other anxiety disorders, a mood disorder, and attention-deficit and disruptive behavior disorders.     

Clinical correlates of quality of life in Tourette syndrome

Tourette syndrome (TS) is a neurodevelopmental disorder involving tics, which is frequently accompanied by comorbid obsessive compulsive (OCD) or attention deficit hyperactivity disorder (ADHD). Individuals with TS often report poor quality of life (QoL) in comparison with the general population. This study investigated the clinical correlates of QoL in young people with TS using a self‐report multidimensional QoL measure, and a range of clinical scales used to assess tic severity and the symptoms of anxiety, depression, OCD, ADHD and other emotional and behavioral symptoms. Symptoms of depression, OCD, and ADHD appeared to have a widespread negative impact on QoL, but poorer QoL was not associated with increased tic severity. Greater emotional and behavioral difficulties, including symptoms of OCD, were among the best predictors of poor QoL in young people with TS. © 2010 Movement Disorder Society     

Compulsive phenomena in children with tic disorder and attention deficit-hyperactive disorder

Tic disorders (TD), obsessive-compulsive disorders (OCD) and attention-deficit/hyperactivity disorder (ADHD) are often associated with deficits of impulse control and aggressive behavior. Tic disorders and OCD are closely related on epidemiological, psychopathological and neurobiological levels, whereas ADHD and OCD phenomena seem to be at opposite poles. Research evidence on the clinical significance of associated obsessive-compulsive behavior is reviewed and linked to our own new data. Thus the analyses of a worldwide database on Tourette's Syndrome (TS) (N = 4,833) showed that that the associated symptomatology of the OCD spectrum has to emphasized. In further investigations, premonitory sensorimotor phenomena reminiscent of OCD were more frequent in children with tic disorders as they grew older. Obsessive-compulsive behavior concomitant with TS was particularly associated with impulsive and aggressive behavior, as well as with depression and anxiety. The data suggest a reduced serotonergic transmission. Self-reports by children with ADHD, as opposed to those by their parents, mentioned a significantly higher quantitative degree of OC phenomena than those by children with TS. These findings suggest that OC symptoms in children with ADHD have so far been neglected in assessments by others. In summary, a complex psychopathological pattern of tic, OC behavior, impulsivity and internalizing symptomatology emerges that requires discriminating assessment and treatment.     

Tic disorders: Administrative prevalence and co-occurrence with attention-deficit/hyperactivity disorder in a German community sample

Coexistence of tics and attention-deficit/hyperactivity disorder (ADHD) has important clinical and scientific implications. Existing data on the co-occurrence of tic disorders, Tourette Syndrome (TS), and ADHD are largely derived from small-scale studies in selected samples and therefore heterogeneous. The Nordbaden project captures the complete outpatient claims data of more than 2.2 million persons, representing 82% of the regional population in 2003. Based upon the number of diagnosed cases of tic disorders, TS, and ADHD, we determined 12-months administrative prevalence rates as well as rates of co-occurrence. Both tic disorders and ADHD were diagnosed most often in the age group 7–12 years (any tic disorder: 0.8%; ADHD: 5.0%). With increasing age, the administrative prevalence difference in favor of males disappeared, with tic disorders being somewhat more frequently reported in females than males in the age groups above 30 years. The highest rate of ADHD co-occurring with tic disorders was found in adolescents (age 13–18 years, 15.1%). Tic disorders were observed in 2.3% of patients with ADHD. Administrative prevalence rates of tic disorders and TS were substantially lower compared to rates found in community-based epidemiological studies, suggesting that a large number of cases remain undetected and untreated under present conditions of routine outpatient care.     

Antineuronal antibodies in a group of children with obsessive-compulsive disorder and Tourette syndrome

An autoimmune hypothesis has been suggested for early onset obsessive-compulsive disorder and Tourette syndrome. The term: Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) has been proposed as an aetiological subtype of OCD and TS, related to a Group A beta haemolytic streptococcal (GABHS) infection that triggers an autoimmune response. Antineural antibodies have been studied and found in the sera of some patients with these disorders, and they are thought to cross-react with streptococcal and basal ganglia antigens. The present study included 32 prepubertal-onset OCD patients, 21 with TS diagnosis (some of them meeting criteria for PANDAS) and 19 normal children, all aged between 9 and 17 years. Antibodies were assayed by immunohistochemistry and immunoblot. Special attention was paid to the methodology and a high serum dilution was used to minimize non-specific binding. No anti-basal ganglia antibodies were detected by immunohistochemistry in any of the samples. Two proteins, with approximate molecular weights of 86 kDa and 55 kDa, were found in sera from 7 patients. Though the study supports the hypothesis of an autoimmune process underlying OCD or TS in some patients, further research is needed.     

Association of cortical disinhibition with tic, ADHD, and OCD severity in Tourette syndrome.

Hyperkinetic disorders may involve excess excitatory output from thalamus to cerebral cortex. Case-control, neurophysiological studies in persons with Tourette Syndrome (TS), Attention Deficit Hyperactivity Disorder (ADHD), and Obsessive-Compulsive Disorder (OCD) support this model. To compare the strength of association between motor cortex inhibition and tic, ADHD, and OCD severity in TS, we used transcranial magnetic stimulation to measure motor cortex inhibition in 36 children and adults with TS. Current symptom severity was assessed with standard clinical rating scales and compared with neurophysiological measures using correlational and multivariate regression analyses. Severity of ADHD symptoms and motor tics were associated significantly and independently with short interval intracortical inhibition (SICI) (r(2) = 0.50; F[2,27] = 13.7; P < 0.001), particularly in subjects not taking neuroleptics (r(2) = 0.68; F[2,17] = 17.8; P < 0.0001). The correlation of cortical disinhibition was greater with ADHD symptoms severity (r = 0.53; P = 0.003) than with tic severity (r = 0.42; P = 0.02), suggesting that in TS, the association between SICI and ADHD symptoms may be more consistent or direct than the association between SICI and tics.     

Is parental report of upper respiratory infection at the onset of obsessive-compulsive disorder suggestive of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection?

The diagnosis of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) requires a prospectively determined association between group A beta-hemolytic streptococcal (GABHS) infection and obsessive-compulsive disorder (OCD) or tic disorder. Screening for GABHS infection imposes a significant burden on both patient and clinician. To heighten the index of suspicion for PANDAS, it would be useful to know if parent-reported upper respiratory infection (URI) is associated with PANDAS symptoms or associated characteristics. Eighty-three consecutive, clinically referred patients aged 6 to 17 years with a primary diagnosis of OCD and their primary caregivers were asked about URI signs and symptoms at the time of OCD onset, PANDAS symptoms, OCD and tic symptoms, comorbidity, and putative PANDAS risk factors. Specific inquiry regarding URI symptoms proved more informative than general inquiry. In the URI present versus URI absent group, more patients experienced a sudden rather than insidious onset of symptoms. Additionally, more patients with a URI plus sudden onset exhibited a comorbid tic disorder. Until validated biomarkers permit retrospective diagnosis, a history that OCD began around the time of a URI should clue the clinician to look prospectively for PANDAS. Additional research is required to define the boundaries of PANDAS and to develop psychometrically reliable and valid diagnostic strategies.     

A family study of juvenile obsessive-compulsive disorder.

OBJECTIVES: To determine whether juvenile obsessive-compulsive disorder (OCD) is familial and whether the rate of Tourette syndrome (TS) and tic disorders is higher among relatives of patients with OCD than among relatives of controls subjects. METHOD: We assessed first-degree relatives of 35 juvenile OCD probands (aged 16 years or less) and 34 matched, psychiatrically unaffected control subjects, using the Diagnostic Interview for Children and Adolescents-Revised (DICA-R) (unpublished), a Questionnaire for tic disorders, the Children's Version of Leyton's Obsessional Inventory (CV-LOI), and the Children's Version of the Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Similarly, we assessed adult relatives, using the Schedule for Clinical Assessment in Neuropsychiatry (SCAN), Leyton's Obsessional Inventory (LOI), the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and a Questionnaire for tic disorders. The diagnoses were determined by consensus, using DSM-III-R criteria. We calculated age-corrected morbid risk, using Weinberg's method. RESULTS: The morbid risk for OCD among the relatives of OCD probands was 4.96%, while none of the relatives of unaffected control subjects had OCD. We did not diagnose TS in any of the relatives of either OCD probands or control subjects. We diagnosed chronic motor tic disorders in only 1 of the relatives of OCD probands, while none of the relatives of control subjects had any tic disorder. CONCLUSION: Most juvenile cases of OCD are nonfamilial and unrelated to tic disorders, while only a few are familial. There is a need to re-examine the issue of familiality in cases of OCD, as well as its relation to TS, using larger community samples to better understand the hypotheses of familial transmission and comorbidity with tic disorders.     

Parental psychopathology and offspring attention-deficit/hyperactivity disorder in a nationwide sample

ObjectiveTo study the associations between a wide range of parental psychiatric disorders and offspring attention-deficit/hyperactivity disorder (ADHD).MethodThis study is based on a nested case–control design. The association between parental registered psychiatric diagnoses and offspring ADHD was examined adjusting for socioeconomic and prenatal factors. Data was linked from Finnish nationwide registers. The cases (n = 10,409) were all the children born between years 1991 and 2005 in Finland and diagnosed with ADHD by the end of 2011. Four controls without ADHD (n = 39,124) were matched for every case by sex, age and place of birth. Main outcomes were adjusted odds ratio (aOR) for parental diagnosis of cases vs controls. Analyses were further stratified by sex. Disorders diagnosed before and after birth were analyzed separately.ResultsThe odds ratio for ADHD increased when only mother (aOR 2.2, 95% CI 2.0–2.3), only father (aOR 1.7, 95% CI 1.6–1.8) and both parents (aOR 3.6, 95% CI 3.3–4.0) were diagnosed. Maternal diagnosis showed stronger association than paternal. The weight of association between several parental disorders and offspring ADHD were similar. Maternal psychopathology overall showed stronger associations with girls than boys with ADHD. The diagnoses registered after birth did not show stronger association than the diagnoses registered before. Conclusions: Maternal psychopathology showing stronger association than paternal implies that environmental factors or their interaction with genetic factors partly mediates the risk of parental psychopathology. Similar associations between several maternal psychiatric disorders and offspring ADHD points towards the need for investigating some common mother-related risk factors.     

Psychiatric disorders in first-degree relatives of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)

OBJECTIVE: To determine the rates of psychiatric disorders in the first-degree relatives of children with infection-triggered obsessive-compulsive disorder (OCD) and/or tics (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; PANDAS). METHOD: The probands of this study were 54 children with PANDAS (n = 24 with a primary diagnosis of OCD; n = 30 with a primary diagnosis of a tic disorder). One hundred fifty-seven first-degree relatives (100 parents [93%] and 57 siblings [100%]) were evaluated for the presence of a tic disorder. One hundred thirty-nine first-degree relatives (100 parents [93%] and 39 of 41 siblings over the age of 6 [95%]) were evaluated with clinical and structured psychiatric interviews to determine the presence of subclinical OCD, OCD, and other DSM-IV Axis I disorders. RESULTS: Twenty-one probands (39%) had at least one first-degree relative with a history of a motor or vocal tic; 6 mothers (11%), 9 fathers (19%), and 8 siblings (16%) received this diagnosis. Fourteen probands (26%) had at least one first-degree relative with OCD; 10 mothers (19%), 5 fathers (11%), and 2 siblings (5%), received this diagnosis. An additional 8 parents (8%) and 3 siblings (8%) met criteria for subclinical OCD. Eleven parents (11%) had obsessive-compulsive personality disorder. CONCLUSIONS: The rates of tic disorders and OCD in first-degree relatives of pediatric probands with PANDAS are higher than those reported in the general population and are similar to those reported previously for tic disorders and OCD. Further study is warranted to determine the nature of the relationship between genetic and environmental factors in PANDAS.     

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.     

The role of comorbid major depressive disorder in the clinical presentation of adult ADHD

Most adults with attention-deficit/hyperactivity disorder (ADHD) are not recognized and remain untreated, although a large fraction of these individuals are diagnosed and treated for other comorbid mental disorders, such as major depressive disorder (MDD). The fact that MDD is one of the most commonly occurring mental disorders with high comorbidity with adult ADHD raises the question whether such comorbidity is associated with differences in the clinical picture of ADHD. Three hundred and twenty adult ADHD outpatients were evaluated. Diagnoses followed DSM-IV criteria. Interviews to evaluate ADHD and oppositional defiant disorder (ODD) were performed based on the Portuguese version of K-SADS-E. Psychiatric comorbidities were investigated using SCID-IV and MINI. Regression models were applied to test MDD association with clinical and demographic outcomes. Subjects presenting ADHD and MDD had a higher frequency of generalized anxiety disorder and social phobia and a lower frequency of substance dependence, grade repetition and school suspensions, when compared to subjects with ADHD without MDD. Furthermore, adults presenting ADHD and MDD reported higher demand for psychotherapy and pharmacological treatment prior to enrollment in the study when compared to ADHD subjects free of MDD. However, contrary to what could be expected based on these data, the presence of MDD was not associated with an earlier ADHD diagnosis. These results point to the need for research and medical education into an earlier and more efficient ADHD diagnosis in patients who search for mental health care.     

Antineuronal antibody status and phenotype analysis in Tourette's syndrome.

The Gilles de la Tourette syndrome (GTS) spectrum includes psychiatric comorbidities, mainly obsessive-compulsive disorder (OCD) and attention-deficit-hyperactivity disorder (ADHD). The role of environmental factors, e.g., antineuronal antibodies (ANeA), remains unclear. We compared the clinical features of ANeA-positive and ANeA-negative patients in 53 children and 75 adults with GTS. All diagnoses were made according to DSM-IV-TR criteria. A positive ANeA Western immunoblot showed bands for at least 1 of 3 reported striatal antigens (40, 45, and 60 kDa). Twelve children (23%) and 18 adults (25%) with GTS were ANeA-positive. Disease duration, tic phenomenology and severity, frequency of echo/pali/coprophenomena, self-injurious and aggressive behavior, or frequency of OCD comorbidity did not significantly differ between ANeA-positive and negative patients. Similar findings were obtained analyzing separately the three different antibody reactivities. A comorbid diagnosis of ADHD was significantly less frequent in GTS patients positive for the anti-60 kDa antibody only. Using a multivariate logistic regression model, adjusting for age, gender, and age at disease onset, a comorbid diagnosis of ADHD remained inversely associated with anti-60 kDa antibodies (odds ratio = 0.14; P = 0.002; 95% confidence interval 0.04-0.49). ANeA status does not differentiate a specific phenotype of GTS.     

Anxiety disorders and obsessive compulsive disorder 9 months after perinatal loss

ObjectivePerinatal loss (stillbirth after 20 weeks of gestational age or infant death in the first month) impacts one to two infants per hundred live births in the United States and can be a devastating experience for parents. We assessed prevalence of anxiety disorders and obsessive compulsive disorder (OCD) among bereaved and live-birth mothers.MethodsWe collaborated with the Michigan Department of Community Health to survey Michigan mothers with perinatal death or live birth. We measured symptoms of generalized anxiety disorder, social phobia, panic disorder and OCD using validated written self-report screens and collected data on maternal demographics, psychiatric history, social support and intimate partner violence.ResultsA total 609/1400 mothers (44%) participated, returning surveys 9 months postdelivery. Two hundred thirty-two mothers had live birth, and 377 had perinatal loss. In unadjusted analyses, bereaved mothers had higher odds of all four disorders. In logistic regression adjusted for covariates, bereaved mothers still had higher odds of moderate–severe generalized anxiety disorder [odds ratio (OR): 2.39, confidence interval (CI): 1.10–5.18, P= .028] and social phobia (OR: 2.32, CI: 1.52–3.54, P< .0005) but not panic disorder or OCD.ConclusionBereaved mothers struggle with clinically significant anxiety disorders in the first year after perinatal loss; improved identification and treatment are essential to improve mental health for this vulnerable population.     

Pre- and perinatal complications in relation to Tourette syndrome and co-occurring obsessive-compulsive disorder and attention-deficit/hyperactivity disorder

Pre- and perinatal complications have been implicated in the onset and clinical expression of Tourette syndrome albeit with considerable inconsistencies across studies. Also, little is known about their role in co-occurring obsessive-compulsive disorder (OCD) and attention–deficit/hyperactivity disorder (ADHD) in individuals with a tic disorder. Therefore, we aimed to investigate the role of pre- and perinatal complications in relation to the presence and symptom severity of chronic tic disorder and co-occurring OCD and ADHD using data of 1113 participants from the Tourette International Collaborative Genetics study. This study included 586 participants with a chronic tic disorder and 527 unaffected family controls. We controlled for age and sex differences by creating propensity score matched subsamples for both case-control and within-case analyses. We found that premature birth (OR = 1.72) and morning sickness requiring medical attention (OR = 2.57) were associated with the presence of a chronic tic disorder. Also, the total number of pre- and perinatal complications was higher in those with a tic disorder (OR = 1.07). Furthermore, neonatal complications were related to the presence (OR = 1.46) and severity (b = 2.27) of co-occurring OCD and also to ADHD severity (b = 1.09). Delivery complications were only related to co-occurring OCD (OR = 1.49). We conclude that early exposure to adverse situations during pregnancy is related to the presence of chronic tic disorders. Exposure at a later stage, at birth or during the first weeks of life, appears to be associated with co-occurring OCD and ADHD.     

Pharmacotherapy of Tourette's syndrome and associated disorders.

Tourette's syndrome (TS) is a chronic neuropsychiatric disorder characterized by multiform motor and phonic tics. Conditions that are commonly associated with TS include attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). Medications used to treat tics include haloperidol, pimozide, and clonidine. Symptoms of ADHD may respond to clonidine or desipramine. Specific serotonin uptake inhibitors, such as fluoxetine or clomipramine, are used in the treatment of OCD symptoms. The decision to use medication and the monitoring of its impact require careful assessment of the child's overall development and not only the presence of tic symptoms.