Disease relevance of GTS

• Gilles de la Tourette syndrome (GTS) is a sporadic or inherited complex neuropsychiatric disorder characterized by involuntary motor and vocal tics [1].
• Six had movement disorders related to non-tic conditions commonly associated with GTS: four patients had movements associated with OCD, one with ADHD and antisocial behavior, respectively [2].
• Recently, evidence has accumulated supporting the role of autoimmune mechanisms in the aetiology of GTS, suggesting that it is within the paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) spectrum of childhood neurobehavioural disorders [3].
• Chromosomal abnormalities have long been proposed to play a causative role in isolated cases of GTS spectrum phenomena, but confirmation of this hypothesis has yet to be forthcoming [4].
• CONCLUSIONS: ADD, learning problems, stuttering, and speech problems by themselves are not variant forms of GTS [5].

Psychiatry related information on GTS

• The rate of obsessive-compulsive disorder (OCD) was significantly elevated among the subjects with GTS (41.7%) compared with the population point prevalence of OCD (3.4) in those without GTS [6].
• There are paediatric psychological conditions in which rCBF has been undertaken, these include anorexia nervosa, autism, Gilles de la Tourette syndrome (GTS) and attention deficit disorder-hyperactivity (ADHD) [7].
• Psychopathology occurs in approximately 90% of GTS patients, with attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) being common [8].
• Bipolar affective disorder (BAD) and GTS may be related in some individuals [8].
• Depression and depressive symptoms are found to occur in 13% and 76% of GTS patients attending specialist clinics, respectively [8].

High impact information on GTS

• Locating genetic loci by associating the phenotype with DNA translocations, inversions, gain or losses, State et al. identified SLITRK1 as a candidate gene in an individual with GTS and inv(13) (q31.1; q33.1) [9].
• Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder characterized by impairing motor-vocal tics [9].
• In contrast, the rate of attention deficit hyperactivity disorder was only 8.3% compared with the population point prevalence of 3.9% in those individuals without GTS [6].
• Of the 25 SNPs, 3 were associated with GTS at a statistically significant level [10].
• Gilles de la Tourette syndrome (GTS) is a potentially debilitating neuropsychiatric disorder defined by the presence of both vocal and motor tics [4].

Chemical compound and disease context of GTS

• We report recent experiences with treatment with aripiprazole, a novel antipsychotic agent, which not only improved motor and vocal tics but also ameliorated some behavioural symptoms of the GTS cluster [11].
• 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 [12].
• Fasting plasma levels of tryptophan, kynurenine and the pteridines, neopterin and tetrahydrobiopterin were measured in seven patients with Gilles de la Tourette syndrome (GTS) and 10 healthy controls [13].
• This exploratory study was meant to determine the effect of the dopamine (DA) agonist pergolide on Gilles de la Tourette syndrome (GTS) in children and adolescents and to ascertain correlates of pergolide response [14].
• The present study was undertaken to compare measures of psychopathology, personality and blood serotonin between GTS and OCD (without tics), and to investigate whether an OCD spectrum hypothesis is supported for GTS [15].

Biological context of GTS

• We have investigated a GTS family with a complex chromosomal insertion/translocation involving chromosomes 2 and 7 [1].
• We hypothesize that disruption or decreased expression of CNTNAP2 could lead to a disturbed distribution of the K(+) channels in the nervous system, thereby influencing conduction and/or repolarization of action potentials, causing unwanted actions or movements in GTS [1].
• Our genome scan of sibling pair families with GTS found evidence suggestive of linkage to several chromosomal locations [16].
• In this study, we investigate the association of three microsatellite polymorphisms (MOGa, MOGb, MOGc) in the gene for MOG with GTS in 197 family trios collected from southwest China. Linkage disequilibrium between these three markers was observed with the strongest between MOGa and MOGc (D' = 0.541, P = 0.000) [3].
• Segregation analyses suggest that GTS and milder phenotypes are caused by a single dominant gene [17].

Anatomical context of GTS

• These findings suggest that GTS subjects who lack normal basal ganglia structural asymmetries also lack normal functional asymmetries on related neuropsychological measures [18].
• The glycine receptor gene responsible for hyperekplexia and the other neuroreceptor genes examined in this paper are not involved in the etiology of GTS in this large pedigree [19].
• We studied 17 patients with GTS and eight normal controls using volumetric MRI techniques for measuring the caudate nucleus, amygdala, and corpus callosum [20].
• BACKGROUND: Statistical characterization of tic behavior in Gilles de la Tourette syndrome (GTS) may provide insight into the dynamic functioning of the human central nervous system, as well as improve the quantitative assessment of tic symptom severity [21].
• Erythrocyte measures of copper-zinc superoxide dismutase (CuZnSOD) were performed on 11 subjects with a clinical diagnosis of Gilles de la Tourette syndrome (GTS) and 6 healthy controls at specified intervals throughout the day [22].

Associations of GTS with chemical compounds

• Some studies have implicated the D2 and D4 dopamine receptors as having a direct role in the etiology of GTS, but other studies have disputed those findings [23].
• The adrenergic system has been suggested to play a role in GTS based on the reduction of symptoms with the adrenergic receptor agonists, clonidine and guanfacine [16].
• We conducted an open-label trial of fluoxetine (20 to 40 mg/d) for 32 GTS patients with OCD [24].
• The neurotransmitter systems most often thought to be involved in GTS include those involving adrenaline, noradrenaline, and dopamine [25].
• Twenty-six GTS patients (10.5 +/- 2.6 years), experienced clinical response rates of 69% on 3.4 +/- 1.6 mg pimozide and 65% on 3.5 +/- 2.2 mg/day haloperidol [26].

Physical interactions of GTS

• CONCLUSION: Patients with GTS show higher striatal binding of FP-CIT to the striatum in comparison with age- and gender-matched control subjects, indicating that dopamine transporter abnormalities are involved in the pathophysiology of GTS [27].

Other interactions of GTS

• However, the dopamine D2 receptor may modulate the severity of GTS [23].
• We examined the inheritance of polymorphisms in the ADRA2A and ADRA1C genes in 113 nuclear families identified through a GTS proband [16].
• Cultures enriched in CD14-dependent DCs were more potent stimulators of a mixed leukocyte reaction, compared with control GTS cultures containing both types of DCs [28].
• Antigen-presenting function was acquired only when DC maturation was induced from these myelodendritic progenitors with GM-CSF + interleukin-4 or GTS [28].
• In our study both serotonin receptor subunit genes, HTR3A and HTR3B, were examined for sequence variations in GTS patients [29].

Analytical, diagnostic and therapeutic context of GTS

• In community and epidemiological studies, depression in GTS individuals was evident in two of five investigations [8].
• However, it is noted that sample sizes in most of these studies were small, and it is unclear at the present time as to why BAD may be overrepresented among GTS patients [8].
• Depression in people with GTS has been shown to result in a lower quality of life, potentially leading to hospitalization and suicide [8].
• Gilles de la Tourette Syndrome (GTS) has long been known to be familial, and evidence from twin studies indicates that it has a substantial genetic component [16].
• To further characterize the distal breakpoint for a role in GTS, we performed Southern blot hybridization analysis and identified a 6.5-kb SacI junction fragment in the patient's genomic DNA [30].

References