Ruth D. Bruun

Explosive outbursts in children with Tourette's disorder

OBJECTIVE Sudden, explosive outbursts of behavior occur in some children with Tourettes disorder (TD). The etiology of these symptoms is unknown. This study investigated the relationship between explosive outbursts, TD, and its comorbid disorders. METHOD Tic type and severity and the presence of specific comorbid disorders were compared in 37 children with TD and explosive outbursts and 31 children with TD who did not have such symptoms. RESULTS Children with TD and explosive outbursts were more likely to demonstrate significant comorbid conditions, particularly attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and oppositional defiant disorder. Tic type and severity did not appear related to the presence of explosive outbursts. A highly significant relationship was demonstrated between the number of comorbid psychiatric diagnoses and explosive outbursts. CONCLUSIONS Explosive outbursts in children with TD resemble intermittent explosive disorder and may reflect dysregulation of diverse domains of brain function. The presence of such symptoms should alert the clinician to underlying comorbid conditions.

Genome-wide association study of Tourette's syndrome

Tourettes 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.

Self injurious behaviour in Tourette syndrome: correlates with impulsivity and impulse control

Background: Self injurious behaviour (SIB), the deliberate, repetitive infliction of self harm, is present in a wide variety of neuropsychiatric disorders, including Tourette syndrome (TS). Although SIB occurs in up to 60% of individuals with TS, and can cause significant clinical impairment and distress, little is known about its aetiology. Objective: This study examined the relationship between SIB and other behavioural features that commonly co-occur with TS in nearly 300 subjects with TS participating in three genetic studies. SIB, obsessions, compulsions, tic severity, attention deficit hyperactivity disorder related impulsivity, risk taking behaviours, and rages were systematically assessed in all subjects. Methods: Using logistic regression, a best fit model was determined for both mild to moderate SIB and severe SIB. Results: Mild/moderate SIB in TS was correlated with the presence of obsessive and compulsive symptoms such as the presence of aggressive obsessions or violent or aggressive compulsions, and with the presence of obsessive−compulsive disorder and overall number of obsessions. Severe SIB in TS was correlated with variables related to affect or impulse dysregulation; in particular, with the presence of episodic rages and risk taking behaviours. Both mild/moderate and severe SIB were also correlated with tic severity. Conclusions: This study suggests that mild/moderate and severe SIB in TS may represent different phenomena, which has implications for clinical management of these symptoms.

THE COURSE AND PROGNOSIS OF TOURETTE SYNDROME

The view of Tourette syndrome as a lifelong disorder, once held as a certainty, has changed considerably in the past two decades. It is now known that in the majority of cases, tics will ebb in severity and will no longer be problematic in the adult years. This discovery, however, has been accompanied by the realization that Tourette syndrome is a far more complex disorder than was originally discerned and that it has many unanswered questions.

Tic Symptom Profiles in Subjects with Tourette Syndrome from two Genetically Isolated Populations

BACKGROUND Tourette Syndrome (TS) has a complex etiology and wide variability in phenotypic expression. Identifying underlying symptom patterns may be useful for etiological and outcome studies of TS. METHODS Lifetime tic and related symptom data were collected between 1996 and 2001 in 121 TS subjects from the Central Valley of Costa Rica and 133 TS subjects from the Ashkenazi Jewish (AS) population in the US. Subjects were grouped by tic symptoms using an agglomerative hierarchical cluster analysis. Cluster membership was tested for association with available ancillary information (age of onset, tic severity, comorbid disorders, medication treatment and family history). RESULTS Cluster analysis identified two distinct groups in each sample, those with predominantly simple tics (cluster 1), and those with multiple complex tics (cluster 2). Membership in cluster 2 was correlated with increased tic severity, global impairment, medication treatment, and presence of comorbid obsessive-compulsive symptoms in both samples, and with family history of tics, lower verbal IQ, earlier age of onset, and comorbid obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in the AS sample. CONCLUSIONS This study provides evidence for consistent and reproducible symptom profiles in two independent TS study samples. These findings have implications for etiological studies of TS.