Sequence variants in SLITRK1 are associated with Tourette's syndrome.
(49/312)
Tourette's syndrome (TS) is a genetically influenced developmental neuropsychiatric disorder characterized by chronic vocal and motor tics. We studied Slit and Trk-like 1 (SLITRK1) as a candidate gene on chromosome 13q31.1 because of its proximity to a de novo chromosomal inversion in a child with TS. Among 174 unrelated probands, we identified a frameshift mutation and two independent occurrences of the identical variant in the binding site for microRNA hsa-miR-189. These variants were absent from 3600 control chromosomes. SLITRK1 mRNA and hsa-miR-189 showed an overlapping expression pattern in brain regions previously implicated in TS. Wild-type SLITRK1, but not the frameshift mutant, enhanced dendritic growth in primary neuronal cultures. Collectively, these findings support the association of rare SLITRK1 sequence variants with TS. (+info)
Caudate volumes in childhood predict symptom severity in adults with Tourette syndrome.
(50/312)
BACKGROUND: Most children with Tourette syndrome (TS) experience a marked decline in the severity of tic symptoms during adolescence. Currently no clinical measures can predict whose tic symptoms will persist into adulthood. Previous cross-sectional imaging studies have identified reduced caudate nucleus volumes in subjects with TS. OBJECTIVE: To evaluate whether caudate nucleus volumes in childhood can predict the severity of tic or obsessive-compulsive symptoms at follow-up in early adulthood. METHODS: In a prospective longitudinal study, clinical status and basal ganglia volumes of 43 children with TS were measured on high-resolution magnetic resonance images before age 14 years. Follow-up clinical assessments were conducted after age 16 years, an average of 7.5 years later. Linear regression and Tobit regression analyses were used to assess the association of basal ganglia volumes measured in childhood with the severity of tic and obsessive-compulsive disorder (OCD) symptoms at the time of childhood MRI and at follow-up in early adulthood. RESULTS: Volumes of the caudate nucleus correlated significantly and inversely with the severity of tic and OCD symptoms in early adulthood. Caudate volumes did not correlate with the severity of symptoms at the time of the MRI scan. CONCLUSIONS: Caudate volumes in children with Tourette syndrome predict the severity of tic and obsessive-compulsive symptoms in early adulthood. This study provides compelling evidence that morphologic disturbances of the caudate nucleus within cortico-striatal-thalamo-cortical circuits are central to the persistence of both tics and obsessive-compulsive symptoms into adulthood. (+info)
Tourette syndrome: not just a tic disorder.
(51/312)
Although tics are considered the hallmark of Tourette syndrome, arguably tics may not be the only or primary presenting symptom. For many children diagnosed with Tourette syndrome irritability, frustration intolerance, hyperactivity, inattention, ritual behavior or other difficulties may have been present a number of years before the appearance of tics. Children with Tourette syndrome are often highly co-morbid with attention deficit-hyperactivity disorder, obsessive compulsive symptoms, and other related behavioral problems that should be detected and treated effectively. Therefore tics should not be the sole indicator or receive over emphasis in the detection and treatment of Tourette syndrome. (+info)
Adulthood outcome of tic and obsessive-compulsive symptom severity in children with Tourette syndrome.
(52/312)
BACKGROUND: Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder that is characterized by both motor and phonic tics. One half to two thirds of children with TS experience a reduction or complete resolution of tic symptoms during adolescence. At least one third of adults with TS have comorbid obsessive-compulsive disorder (OCD). OBJECTIVES: To clarify the clinical course of tic and OCD symptoms in children with TS and determine if baseline clinical measurements in childhood are associated with future symptom severity in late adolescence and early adulthood. DESIGN: Prospective cohort study. SETTING: Yale Child Study Center tic and OCD outpatient specialty clinic. PARTICIPANTS: Forty-six children with TS who received a structured clinical evaluation prior to age 14 years. MAIN OUTCOME MEASURES: Expert-rated tic and OCD symptom severity at follow-up interview an average of 7.6 years later (range, 3.8-12.8 years). RESULTS: Eighty-five percent of subjects reported a reduction in tic symptoms during adolescence. Only increased tic severity in childhood was associated with increased tic severity at follow-up. The average age at worst-ever tic severity was 10.6 years. Forty-one percent of patients with TS reported at one time experiencing at least moderate OCD symptoms. Worst-ever OCD symptoms occurred approximately 2 years later than worst-ever tic symptoms. Increased childhood IQ was strongly associated with increased OCD severity at follow-up. CONCLUSION: Obsessive-compulsive disorder symptoms in children with TS became more severe at a later age and were more likely to persist than tic symptoms. (+info)
Interhemispheric connectivity and executive functioning in adults with Tourette syndrome.
(53/312)
The prefrontal cortex (PFC) is relatively smaller, and the corpus callosum (CC) larger, in adults with Tourette syndrome (TS). The authors explored the possible roles of the PFC and the CC in mediating interhemispheric interference and coordination in TS adults. They measured performance on M. Kinsbourne and J. Cook's (1971) verbal-manual interference task and on the bimanual Purdue Pegboard in 38 adults with TS and 34 healthy adults. Compared with controls, TS subjects were impaired on the bimanual Purdue Pegboard. On the dual task, right-hand performance did not differ between groups, but the normally expected left-hand advantage (opposite hemisphere condition) was absent in TS subjects. In the control group only, better left-hand performance accompanied larger PFC volumes but not CC cross-sectional area. PFC dysfunction might have precluded executive control of interference in the TS group. (+info)
Beck Depression Inventory is a useful screening tool for major depressive disorder in Gilles de la Tourette syndrome.
(54/312)
This study determined the prevalence of and factors associated with comorbid major depressive disorder (MDD) in patients with Gilles de la Tourette syndrome (GTS). How a simple self-report instrument, the Beck Depression Inventory (BDI), correlates with clinical assessment of comorbid MDD in this population was assessed. In a continuous sample of 114 adult patients with GTS, assessed clinically using the Diagnostic and Statistical Manual of Mental Disorders-IV criteria, 26 (23%) patients met criteria for MDD; more severe tics as measured with the Yale Global Tic Severity Scale, conduct disorder in childhood or higher age at the time of assessment were associated with MDD. The BDI score had a high negative predictive value for diagnosis of MDD, but a low positive predictive value. Using the BDI as a screening tool for comorbid MDD in patients with GTS is suggested. (+info)
Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study.
(55/312)
Little is known about the neural correlates of tics and associated urges. In the present study, we aimed to explore the neural basis of tics in patients with Tourette syndrome by using event-related functional MRI (fMRI). Ten patients (6 women, 4 men; age: mean +/- SD = 31 +/- 11.2) were studied while spontaneously exhibiting a variety of motor and vocal tics. On the basis of synchronized video/audio recordings, fMRI activities were analysed 2 s before and at tic onset irrespective of the clinical phenomenology. We identified a brain network of paralimbic areas such as anterior cingulate and insular cortex, supplementary motor area (SMA) and parietal operculum (PO) predominantly activated before tic onset (P < 0.05, corrected for multiple comparisons). In contrast, at the beginning of tic action, significant fMRI activities were found in sensorimotor areas including superior parietal lobule bilaterally and cerebellum. The results of this study indicate that paralimbic and sensory association areas are critically implicated in tic generation, similar to movements triggered internally by unpleasant sensations, as has been shown for pain or itching. (+info)
Enhanced cognitive control in young people with Tourette's syndrome.
(56/312)
Tourette's syndrome (TS) is a neurodevelopmental disorder characterized by the presence of chronic vocal and motor tics. Tics are sudden, highly stereotyped, movements that can be simple or complex in appearance. Since patients with TS have difficulties preventing unwanted movements, one might expect that their ability to voluntarily control goal-directed movements would be similarly poor. Indeed, it has been suggested that TS sufferers are impaired at inhibiting reflexively triggered movements and in rapidly selecting or switching between different motor sets. This idea is consistent with current views on the neurological basis of TS that posit a dysfunction of the neural circuits linking the frontal lobes and the striatum. These circuits are known to be involved in the voluntary control of action. By using an oculomotor switching task, we show for the first time that young people with TS exhibit paradoxically greater levels of cognitive control over their movements than their age-matched controls. This finding is consistent with an increased need to monitor and control movements and may indicate a subcortical locus for the triggering of tics. It also suggests that the constant need to suppress tics could have resulted in an enhancement of the executive processes involved in inhibitory control. (+info)