Previous studies have demonstrated that Gilles de la Tourette syndrome (TS) is a familial disorder and that chronic tics (CT) and obsessive compulsive disorder (OCD) appear to be etiologically related to the syndrome. In the present study we report the results from a study of 338 biological relatives of 86 TS probands, 21 biologically unrelated relatives of adopted TS probands, and 22 relatives of normal subjects. The 43 first-degree relatives of the adopted TS and normal probands constituted a control sample. The rates of TS, CT, and OCD in the total sample of biological relatives of TS probands were significantly greater than in the relatives of controls. In addition, the morbid risks of TS, OCD, and CT were not significantly different in families of probands with OCD when compared to relatives of probands without OCD. These findings provide further evidence that OCD is etiologically related to TS.

Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P<5 × 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P=1.85 × 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (P=3.6 × 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.

Symptoms of Tourette's syndrome vary in frequency and intensity. Although such variability may be the result of deficits in the underlying neurological system, tic expression can also be systematically impacted by contextual factors. This article reviews research on the impact of several contextual factors on tic expression and discusses implications for future research and treatment development.

This report describes an adolescent boy who has Tourette's syndrome and developed a subtle but significant increase in vocal tics after an 8-month respite. The increase in vocal tics was associated with an acute increase in psychological stressors and resulted in recurrent air swallowing, which, in turn, caused abdominal cramping, eructation, and flatus, eventually leading to aeroenteria. Air swallowing was recognized only after a second hospital admission for recurrent ileus. Air swallowing and associated symptoms were mitigated by reinstitution of psychopharmacologic treatment and an increase in the patient's self-awareness of the air-swallowing behavior. Clinically significant air swallowing has not been described previously in Tourette syndrome or a tic disorder. This case is important for pediatricians and pediatric gastroenterologists because either may be the first to evaluate a child or an adolescent with unexplained recurrent ileus. This report also documents the importance of the connection between the brain and the body.

OBJECTIVE:Gilles de la Tourette's syndrome is a well-characterized disorder with clear DSM-IV criteria. However, the great deal of clinical variability across patients may represent an underlying etiologic complexity. Issues of phenotypic heterogeneity are particularly critical to current efforts at mapping genes involved in this syndrome. METHOD:Lifetime tic symptom data were obtained from direct structured interviews of 85 Tourette's disorder probands. Information on 29 tic symptoms was elicited. The probands' tic symptoms were grouped by using agglomerative hierarchical clustering, with no a priori assumptions concerning the relatedness of symptoms. Scores for the probands' symptom clusters were used as variables in a principal-component factor analysis. The relationships of the resulting factor scores to comorbidity in probands and recurrence risks in relatives were examined. In addition, intraclass correlations were calculated for within-family factor scores of 36 families. RESULTS:Four significant factors were identified: 1) aggressive phenomena (e.g., kicking, temper fits, argumentativeness), 2) purely motor and phonic tic symptoms, 3) compulsive phenomena (e.g., touching of others or objects, repetitive speech, throat clearing), and 4) tapping and absence of grunting. Analysis of the symptom loadings, comorbidity, recurrence risks, and within-family correlations indicate that these factors represent a valid structure with clinical and biological relevance. CONCLUSIONS:In this symptom-based factor analysis of Tourette's disorder, four factors accounted for 61% of the phenotypic symptom variance in Tourette's disorder probands and their first-degree relatives. Three of these factors may indicate the presence of heritable components of the Tourette's disorder phenotype.

Tourette syndrome (TS) is a neurological disorder characterized by highest familial recurrence rate among neuropsychiatric diseases with complicated inheritance. Recurrence of Tourette syndrome was frequently observed in clinical. Unexpectedly, the mechanism of recurrence of Tourette syndrome was failure to elucidate. Here, we first shown that lipopolysaccharide(LPS) may played an important role in the recurrence of Tourette syndrome. The TS model in rats was induced by DOI (the selective 5-HT2A/2C agonist 1-(2, 5-dimethoxy-4-iodophenyl) -2- aminopropane). The rats were randomly divided into 4 groups:(1)Control;(2) Control + LPS; (2)TS; (3)TS + LPS. The results demonstrated that the LPS treatment significantly increased stereotypic score and autonomic activity. LPS treatment also significantly increased inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum and striatum. Also, highly expressed TLR4, MyD88, P-NF-κBp65, P-IκBα in TS rats were increased respectively by LPS treatment as indicted in western blot analysis and immunohistochemistry analysis. Thus, it was supposed that lipopolysaccharide(LPS) may played an important role in the recurrence of Tourette syndrome and its mechanism was related to TLR/NF-κB pathway.

Many patients, parents of children with Tourette's disorder, and professionals have suggested that following a period of suppression, tics will rebound to a rate that will exceed the average rate of occurrence. At present, there are no empirical data to support or refute such an effect. This experiment utilized an A-B-A design with replication to test this hypothesized effect. Following baseline observation, participants were instructed to refrain from exhibiting tics while watching videotapes, engaging in conversation, or while alone in a room with no activity. Observation continued following the suppression phase. Results of this experiment showed suppression of tics in almost one half of all sessions, with adults demonstrating suppression more frequently. Furthermore, results of this experiment failed to support a commonly held perception that following a period of voluntary suppression tics will rebound to a rate that will exceed the average rate of occurrence.

Exposure and response prevention (ER), a behavioral treatment program consisting of exposure to premonitory sensory experiences during prolonged tic suppression, was shown to be a promising new treatment for tics in Tourette's syndrome (TS). In this study, the commonly reported paradoxical increase in tic frequency following voluntary tic suppression, i.e., rebound phenomenon, was examined. Tic frequency was rated in 20 TS patients during 15-minute videotaped conversations taken both before and following 10 ER sessions. In addition, tic frequency was obtained at home by family members of the patients during 15-minute daily tic frequency registrations. Ratings following ER sessions were compared with ratings obtained before the sessions. Neither the ratings at the institute nor the ratings at home supported a rebound effect following ER tic suppression.

Tourette's syndrome (TS) is a neurobiological disorder consisting of motor and vocal tics that are thought to be temporarily suppressible. Many professionals, however, believe that a paradoxical increase in tic frequency (above baseline levels) occurs when efforts to suppress have ceased (i.e., a rebound effect). To date, little research has investigated tic suppression or its effects. This study examined tic frequency during baseline, suppression, and post-suppression conditions using an experimental preparation reported to reliably produce tic suppression in children. Six children with TS and one with chronic tic disorder (CTD) were recorded during baseline and repeated suppression and post-suppression conditions. Tic frequency was significantly lower during suppression as compared to baseline. Although tic frequency during post-suppression was higher than during suppression, it was lower than baseline levels, arguing against a "rebound" effect of tic suppression. Exploratory analyses revealed that scores on the attention problems subscale of the Child Behavior Checklist significantly predicted tic suppressibility. The relationships between age, tic severity, and tic suppressibility were also explored.

IMPORTANCE:Tourette syndrome/chronic tic disorder (TS/CT) and obsessive-compulsive disorder (OCD) overlap in their phenomenological features and often co-occur in affected individuals and families. Understanding how these disorders cluster in families provides important clinical information and is an important step in understanding the causes of these disorders. OBJECTIVE:To determine familial recurrence for TS/CT and OCD using a national epidemiologic sample. DESIGN, SETTING, AND PARTICIPANTS:We performed a population-based study of national health registries in Denmark, including all individuals (n = 1 741 271) born in Denmark from January 1, 1980, through December 31, 2007, and followed up through December 31, 2013. We identified those with TS/CT and/or OCD. MAIN OUTCOMES AND MEASURES:The prevalence of TS/CT and OCD and relative recurrence risk (RRR) for TS/CT or OCD among individuals with an oldest sibling or a parent diagnosed as having TS/CT or OCD compared with individuals without an affected oldest sibling or an affected parent. RESULTS:In this sample, 5596 individuals were diagnosed as having TS/CT; 6191, OCD; and 412, both disorders. The overall cohort prevalence of TS/CT was 0.42% (95% CI, 0.41%-0.43%) and of OCD, 0.84% (95% CI, 0.81%-0.87%). The mean sibling recurrence risk for TS/CT across all birth years was 9.88% (95% CI, 8.02%-12.16%) and for OCD, 4.01% (95% CI, 2.78%-5.76%). The sibling RRR for TS/CT was 18.63 (95% CI, 15.34-22.63). In contrast, the sibling RRR for OCD was 4.89 (95% CI, 3.45-6.93). The parent-offspring RRR for TS/CT was 61.02 (95% CI, 44.43-83.82), whereas the parent-offspring RRR for OCD was 6.25 (95% CI, 4.82-8.11). The sibling and parent-offspring cross-disorder risks were also significant, ranging from 3.20 (95% CI, 2.22-4.62) to 10.27 (95% CI, 5.17-20.39). CONCLUSIONS AND RELEVANCE:Tourette syndrome/CT and OCD cluster in families. The familial aggregation of TS/CT is profound and substantially higher than the familial aggregation for OCD. The recurrence risk estimates provide an important clinical framework for identifying individuals at risk and provide insights into the causes of these disorders.

Tourette disorder (TD) and other chronic tic disorders are neurodevelopmental/neuropsychiatric disorders characterized by motor and/or vocal tics. Family studies indicate that TD strongly aggregates within families and that other chronic tic disorders are biologically related such that studies typically combine them into any chronic tic disorder (CTD). Because of stigma, bullying, and comorbidity with other neuropsychiatric disorders, CTDs can severely impact the quality of life of individuals with these disorders. The genetic architecture of CTDs is complex and heterogeneous, involving a myriad of genetic variants. Thus, providing familial recurrence risks is based on empirical recurrence risk estimates rather than genetic testing. Because empiric recurrence risks for CTDs have not been published, the purpose of this study is to calculate and report these recurrence risks estimates. Based on population prevalence and increased risk to different relatives from a large population-based family study, we calculated the empiric recurrent risk estimate for each relative type (full sibling, parents, offspring, all first-degree, and all second-degree). The recurrence risk estimate for CTDs in first-degree relatives is 29.9% [95% confidence interval (CI) = 23.2-38.5%]. The risk is higher in males, 33.7% (95% CI = 26.2-43.3%), than females, 24.3% (95% CI = 18.9-31.3%). Given the complex, heterogeneous genetic architecture of CTDs, individuals concerned about recurrence risk should be referred to genetic counseling. Such counseling should include discussion of the derivation and limitations of these empiric recurrence risk estimates, including the upper and lower limits of the range of risk.