Disease relevance of Tourette Syndrome

• The dopamine transporter gene (DAT) has been implicated in a variety of disorders, including bipolar disorder, attention-deficit hyperactivity disorder, cocaine-induced paranoia, Tourette's syndrome, and Parkinson's disease [1].
• Gilles de la Tourette's syndrome (GTS) is a genetic disorder characterized by multiple motor and vocal tics, obsessive-compulsive disorder, and attention-deficit disorder [2].
• BACKGROUND: Dopamine agonists and antagonists can reduce abnormal movements and vocalizations (tics) in Tourette syndrome (TS); however, dopamine-responsive abnormal function in specific brain regions has not been directly demonstrated in TS [3].
• While these patients were seen in a specialized movement disorder clinic and may, therefore, represent a population with atypical and more severe symptoms, the high prevalence rate of dystonia (5.0% of all patients with Tourette's syndrome seen in the clinic) suggests that some patients with tics may have an increased risk for dystonia [4].
• Specifically, dopamine (DA) excess and acetylcholine (ACh) deficiency may characterize part of the pathology of several hyperkinetic movement disorders including tardive dyskinesia, Huntington disease, Gilles de la Tourette syndrome, l-dopa dyskinesias, tardive Tourette syndrome, and toxic Tourette syndrome [5].

Psychiatry related information on Tourette Syndrome

• The prevalence of the A1 allele was significantly increased in patients with Tourette's syndrome (44.9%, n = 147), attention deficit hyperactivity disorder (46.2%, n = 104), autism (54.5%, n = 33), alcoholism (42.3%, n = 104), and posttraumatic stress disorder (45.7%, n = 35) [6].
• METHODS: Forty-one children and adolescents with chronic tic disorders, including Tourette disorder and comorbid ADHD, were studied in a 6-week, double-blind, placebo-controlled, parallel trial [7].
• Dysfunction of the D2 dopamine receptors leads to aberrant substance-seeking behaviors (ethanol, drugs, tobacco, and food) and other related behaviors (pathological gambling, Tourette's disorder, attention-deficit/hyperactivity disorder) [8].
• FINDINGS: The literature supports considerable comorbidity of attention deficit hyperactivity disorder with conduct disorder, oppositional defiant disorder, mood disorders, anxiety disorders, learning disabilities, and other disorders, such as mental retardation, Tourette's syndrome, and borderline personality disorder [9].
• We have examined a VNTR polymorphism at the X-linked MAOA gene to test two hypotheses: (1) Do variants of the MAOA gene play a role in any of the behavioral disorders associated with Tourette syndrome or drug abuse [10]?

High impact information on Tourette Syndrome

• Cocaine and Tourette's syndrome [11].
• Treatment of Tourette's syndrome with RO22-1319, a D-2-receptor antagonist [12].
• Red-cell choline and Gilles de la Tourette syndrome [13].
• Purine phosphoribosyltransferase in gilles de la Tourette syndrome [14].
• HGPRT in the Gilles de la Tourette syndrome [15].

Chemical compound and disease context of Tourette Syndrome

• The D2 dopamine receptor and Tourette's syndrome [16].
• Transdermal nicotine patch and potentiation of haloperidol in Tourette's syndrome [17].
• Clonidine in Tourette syndrome [18].
• Comparison of pimozide with haloperidol in Gilles de la Tourette syndrome [19].
• Longlasting improvement of Tourette's syndrome with transdermal nicotine [20].

Biological context of Tourette Syndrome

• Linkage disequilibrium between an allele at the dopamine D4 receptor locus and Tourette syndrome, by the transmission-disequilibrium test [21].
• RESULTS: Complete (theta = 0.0) linkage of Tourette's syndrome with DRD1 was ruled out (lod score of -10.1) when the disease was defined narrowly [22].
• Segregation studies have shown that Gilles de la Tourette Syndrome (GTS) is probably transmitted as an autosomal dominant gene disorder and can therefore be studied by classical linkage analysis to identify susceptibility loci [23].
• Dopamine D2 receptor gene (DRD2) haplotypes and the defense style questionnaire in substance abuse, Tourette syndrome, and controls [24].
• Assignment of the 5HT7 receptor gene (HTR7) to chromosome 10q and exclusion of genetic linkage with Tourette syndrome [25].

Anatomical context of Tourette Syndrome

• METHODS: To compare cerebrospinal fluid (CSF) levels of arginine vasopressin and oxytocin, we collected CSF at midday in a standardized fashion from a total of 83 individuals (29 patients with OCD, 23 patients with Tourette's syndrome, and 31 normal controls) [26].
• Huntington disease and Tourette syndrome. II. Uptake of glutamic acid and other amino acids by fibroblasts [27].
• CONCLUSIONS: Greater putamen dopamine release was seen in adults with Tourette's syndrome than in comparison subjects after a pharmacologic challenge with amphetamine [28].
• Controlled study of erythrocyte choline in Tourette syndrome [29].
• This study aims to investigate whether abnormalities in structural basal ganglia asymmetries in Tourette's syndrome (GTS) have functional significance [30].

Gene context of Tourette Syndrome

• Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome [31].
• These comprehensive analyses, however, fail to identify any common protein coding DAT sequence variant in more than 150 unrelated individuals free of neuropsychiatric disease, 109 individuals meeting City of Hope criteria for Tourette's syndrome, 64 individuals with DSM-IV diagnoses of ethanol dependence, or 15 individuals with ADHD [32].
• Gene content analyses of the breakpoint junctions revealed disruption of a gene (DIBD1 ) at 11q23, a genomic region that has also been implicated in schizophrenia and Tourette syndrome [33].
• Additive effect of three noradrenergic genes (ADRA2a, ADRA2C, DBH) on attention-deficit hyperactivity disorder and learning disabilities in Tourette syndrome subjects [34].
• The present study discovered no DRD1 coding region mutations in any of the Tourette's syndrome or alcohol dependent patients [35].

Analytical, diagnostic and therapeutic context of Tourette Syndrome

• Clonidine has been suggested to be effective in Gilles de la Tourette's syndrome (GTS), but no double-blind study has ever evaluated its effects using objective measures [36].
• METHOD: A double-blind, 24-week, placebo-controlled double crossover study of equivalent dose formulations of haloperidol and pimozide was conducted with 22 subjects, aged 7-16 years, with Tourette's disorder who were randomly assigned to first one active drug treatment and then the other [37].
• ECG changes during haloperidol and pimozide treatment of Tourette's disorder [38].
• The dopamine transporter protein gene (SLC6A3): primary linkage mapping and linkage studies in Tourette syndrome [39].
• Dopamine transporter binding in Gilles de la Tourette syndrome: a [123I]FP-CIT/SPECT study [40].

References