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Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder characterized by motor and vocal tics with an estimated prevalence of 1% in children and adolescents. GTS has high rates of inheritance with many rare mutations identified. Apart from the role of the neurexin trans-synaptic connexus (NTSC) little has been confirmed regarding the molecular basis of GTS. The NTSC pathway regulates neuronal circuitry development, synaptic connectivity and neurotransmission. In this study we integrate GTS mutations into mitochondrial pathways that also regulate neuronal circuitry development, synaptic connectivity and neurotransmission. Many deleterious mutations in GTS occur in genes with complementary and consecutive roles in mitochondrial dynamics, structure and function (MDSF) pathways. These genes include those involved in mitochondrial transport (NDE1, DISC1, OPA1), mitochondrial fusion (OPA1), fission (ADCY2, DGKB, AMPK/PKA, RCAN1, PKC), mitochondrial metabolic and bio-energetic optimization (IMMP2L, MPV17, MRPL3, MRPL44). This study is the first to develop and describe an integrated mitochondrial pathway in the pathogenesis of GTS. The evidence from this study and our earlier modeling of GTS molecular pathways provides compounding support for a GTS deficit in mitochondrial supply affecting neurotransmission.

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder characterized by motor and vocal tics with an estimated prevalence of 1% in children and adolescents. GTS has high rates of inheritance with many rare mutations identified. Apart from the role of the neurexin trans-synaptic connexus (NTSC) little has been confirmed regarding the molecular basis of GTS. The NTSC pathway regulates neuronal circuitry development, synaptic connectivity and neurotransmission. In this study we integrate GTS mutations into mitochondrial pathways that also regulate neuronal circuitry development, synaptic connectivity and neurotransmission. Many deleterious mutations in GTS occur in genes with complementary and consecutive roles in mitochondrial dynamics, structure and function (MDSF) pathways. These genes include those involved in mitochondrial transport (NDE1, DISC1, OPA1), mitochondrial fusion (OPA1), fission (ADCY2, DGKB, AMPK/PKA, RCAN1, PKC), mitochondrial metabolic and bio-energetic optimization (IMMP2L, MPV17, MRPL3, MRPL44). This study is the first to develop and describe an integrated mitochondrial pathway in the pathogenesis of GTS. The evidence from this study and our earlier modeling of GTS molecular pathways provides compounding support for a GTS deficit in mitochondrial supply affecting neurotransmission. [ABSTRACT FROM AUTHOR]

Background: To evaluate the long-term efficacy, prognostic factors, and safety of posteroventral globus pallidus internus deep brain stimulation (DBS) in patients with refractory Tourette syndrome (RTS)., Methods: This retrospective study recruited 61 patients with RTS who underwent posteroventral globus pallidus internus (GPi) DBS from January 2010 to December 2020 at the Chinese People's Liberation Army General Hospital. The Yale Global Tic Severity Scale (YGTSS), Yale-Brown Obsessive-Compulsive Scale (YBOCS), Beck Depression Inventory (BDI), Gilles de la Tourette Syndrome Quality-of-Life Scale (GTS-QOL) were used to evaluate the preoperative and postoperative clinical condition in all patients. Prognostic factors and adverse events following surgery were analyzed., Results: Patient follow up was conducted for an average of 73.33 ± 28.44 months. The final postoperative YGTSS (32.39 ± 22.34 vs 76.61 ± 17.07), YBOCS (11.26 ± 5.57 vs 18.31 ± 8.55), BDI (14.36 ± 8.16 vs 24.79 ± 11.03) and GTS-QOL (39.69 ± 18.29 vs 78.08 ± 14.52) scores at the end of the follow-up period were significantly lower than those before the surgery (p < 0.05). While age and the duration of follow-up were closely related to prognosis, the disease duration and gender were not. No serious adverse events were observed and only one patient exhibited symptomatic deterioration., Conclusions: Posteroventral-GPI DBS provides long-term effectiveness, acceptable safety and can improve the quality of life in RTS patients. Moreover, DBS is more successful among younger patients and with longer treatment duration., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Tourette syndrome (TS) is a severe neuropsychiatric disorder characterized by recurrent, involuntary physical and verbal tics. With a prevalence as high as 1% in children, a deeper understanding of the etiology of the disorder and contributions to risk is critical. Here, we cover the current body of knowledge in scientific literature regarding the genetics of TS. We first review the history and diagnostic criteria for TS cases. We then cover the prevalence, and begin to address the etiology of the disorder. We highlight long-standing evidence for a genetic contribution to TS risk from epidemiology studies focused on twins, families, and population-scale data. Finally, we summarize current large-scale genetic studies of TS along specific classes of genetic variation, including common variation, rare copy number variation, and de novo variation that impact protein-coding sequence. Although these variants do not account for the entirety of TS genetic risk, current evidence is clear that each class of variation is a factor in the overall risk architecture across TS cases.

Background: Tourette syndrome (TS) is a complex neuropsychiatric disorder coupled with obvious genetic heterogeneity. Studies in recent years have confirmed the association of SLITRK genes with sensory and neuropsychiatric diseases. To detect whether SLITRK6 is involved in the progress of TS, a family-based association study was performed to explore the possible genetic association between SLITRK6 and TS in the Chinese Han population., Methods: We genotyped 399 TS nuclear families trios, and then analyzed three tag SLITRK6 single nucleotide polymorphisms using the transmission disequilibrium test (TDT) haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods., Results: The TDT showed no statistically significant allele transfer for the three polymorphisms. The HRR and HHRR also showed a negative association., Conclusions: Despite the results suggesting that these polymorphisms may not be associated with susceptibility to TS in the Chinese Han population, we are still unable to determine the potential role of SLITRK6 in the pathogenesis of TS. Furthermore, the results still need to be confirmed in a larger sample size and in different populations., (© 2020 John Wiley & Sons, Ltd.)

Background: Maternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences., Methods: A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models., Results: PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31-1.99), ASD: aHR = 2.02 (95% CI 1.45-2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19-1.57), ASD: aHR = 1.46 (95% CI 1.21-1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys., Conclusions: Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.

Tourette syndrome is a heterogeneous disorder. The genetic basis is complex, and both in utero and ex utero environmental factors may modify the phenotypic expression of the disorder. Inflammation related to aberrations in immune activation appears to play a pathogenic role in some cases. Multiple neurochemical pathways are involved. Rather than being a pure movement problem, tics are now understood to also have a sensory component. This has resulted in new psychological therapeutic strategies and other potential treatments. Furthermore, comorbidities are common, particularly attention-deficit hyperactivity disorder, anxiety and obsessive-compulsive disorder, and often cause more difficulties than the tics. The approach to treatment is dependent on the degree and types of impairment. For many patients, education, acceptance and understanding are all that is needed. In more severe cases, psychological and/or pharmacological interventions may be indicated. In this article, the clinical features and pathophysiology of Tourette syndrome are reviewed, and a pragmatic management approach is discussed., (© 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Tourette syndrome (TS) is thought to involve dopaminergic disturbances, but the nature of those disturbances remains controversial. Existing hypotheses suggest that TS involves 1) supersensitive dopamine receptors, 2) overactive dopamine transporters that cause low tonic but high phasic dopamine, 3) presynaptic dysfunction in dopamine neurons, or 4) dopaminergic hyperinnervation. We review evidence that contradicts the first two hypotheses; we also note that the last two hypotheses have traditionally been considered too narrowly, explaining only small subsets of findings. We review all studies that have used positron emission tomography and single-photon emission computerized tomography to investigate the dopaminergic system in TS. The seemingly diverse findings from those studies have typically been interpreted as pointing to distinct mechanisms, as evidenced by the various hypotheses concerning the nature of dopaminergic disturbances in TS. We show, however, that the hyperinnervation hypothesis provides a simple, parsimonious explanation for all such seemingly diverse findings. Dopaminergic hyperinnervation likely causes increased tonic and phasic dopamine. We have previously shown, using a computational model of the role of dopamine in basal ganglia, that increased tonic dopamine and increased phasic dopamine likely increase the propensities to express and learn tics, respectively. There is therefore a plausible mechanistic link between dopaminergic hyperinnervation and TS via increased tonic and phasic dopamine. To further bolster this argument, we review evidence showing that all medications that are effective for TS reduce signaling by tonic dopamine, phasic dopamine, or both., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Tourette disorder is a developmental neuropsychiatric condition characterized by vocal and motor tics that can range in severity from mild to disabling. It represents one end of a spectrum of tic disorders and is estimated to affect 0.5-0.7% of the population. Accumulated evidence supports a substantial genetic contribution to disease risk, but the identification of genetic variants that confer risk has been challenging. Positive findings in candidate gene association studies have not replicated, and genomewide association studies have not generated signals of genomewide significance, in large part because of inadequate sample sizes. Rare mutations in several genes have been identified, but their causality is difficult to establish. As in other complex neuropsychiatric disorders, it is likely that Tourette disorder risk involves a combination of common, low-effect and rare, larger-effect variants in multiple genes acting together with environmental factors. With the ongoing collection of larger patient cohorts and the emergence of affordable high-throughput genomewide sequencing, progress is expected to accelerate in coming years., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose of Review: Describe developments in the etiological understanding of Tourette syndrome., Recent Findings: Tourette syndrome is a complex heterogenous clinical syndrome, which is not a unitary entity. Pathophysiological models describe gamma-aminobutyric acid-ergic-associated disinhibition of cortico-basal ganglia motor, sensory and limbic loops. MRI studies support basal ganglia volume loss, with additional white matter and cerebellar changes. Tourette syndrome cause likely involves multiple vulnerability genes and environmental factors. Only recently have some vulnerability gene findings been replicated, including histidine decarboxylase and neurexin 1, yet these rare variants only explain a small proportion of patients. Planned large genetic studies will improve genetic understanding. The role of inflammation as a contributor to disease expression is now supported by large epidemiological studies showing an association with maternal autoimmunity and childhood infection. Investigation of blood cytokines, blood mRNA and brain mRNA expression support the role of a persistent immune activation, and there are similarities with the immune literature of autistic spectrum disorder. Current treatment is symptomatic, although there is a better appreciation of factors that influence treatment response., Summary: At present, therapeutics is focused on symptom-based treatments, yet with improved etiological understanding, we will move toward disease-modifying therapies in the future.

Tourette syndrome (TS) is a neuropsychiatric disorder with the onset in childhood. TS is a form of tic disorders, and characterized by the motor and vocal tics, and comorbidities such as attention deficit hyperkinetic and obsessive compulsive disorders. These symptoms appear age dependently, showing a wax and wane course, and subside or abolish by the late teens. Pathophysiology of TS involves the dysfunction of both motor and non-motor basal ganglia-thalamo-cortical circuitries. The nigrostriatal dopamine (DA) system takes the exponential decrement at the striatum. In TS, this decrement is accelerated in association with DA-D2 receptor super-sensitivity, which disinhibits the descending and ascending output pathways of the basal ganglia. Disinhibited motor basal ganglia-thalamo-cortical circuitries develop the specific tics according to the target sites. Hypofunction of the 5-hydroxytriptophan (5-HT) neurons of the brainstem innervate the striatum involved in non-motor basal ganglia-thalamo-cortical circuitries and cause the obsessive compalsive disorder and other behavioral disorders. The associated DA-D2 receptor supersensitivity is assumed to be a consequence of the developmental abnormalities and not due to denervation supersensitivity. The treatments of TS aim to correct the 5-HT hypofunction by improving the environmental factors and super-sensitized DA receptors medically by a small dose of levodopa and/or aripiprazole.

Gilles de la Tourette syndrome is a chronic neuropsychiatric movement disease with combined motor tics and at least one vocal tic for a minimum period of 1 year. It typically begins in the childhood (under 18 years of age).Most of the patients with Tourette syndrome have comorbidities, which often impair their quality of life more than the tics themselves.There are reported abnormalities in the cortico-striato-thalamo-cortical regions as well as in the neurotransmission of dopamine and other neurotransmission systems. Genetic and non genetic factors are discussed.In each patient psychoeducation is the basis of treatment. Specific treatment is only needed in more severe tic disorders which cause evident psychosocial impairment.Behavior therapy should be tried before drug treatment. For very severely affected adults, deep brain stimulation is a further treatment option., Competing Interests: Interessenkonflikt: Die Autorin Kirsten Müller-Vahl erklärt, dass sie innerhalb der letzten 3 Jahre Mitglied im Sachverständigenausschuss für Betäubungsmittel der Bundesopiumstelle und im wissenschaftlichen Beirat der Fundación CANNA war sowie 2. Vorsitzende der International Association for Cannabinoid Medicines (IACM) ist. Sie ist beratend tätig für Abide Pharmaceutics, Inc., Prahealthsciences und Therapix Biosciences und erhielt Forschungsunterstützung von der Deutschen Forschungsgemeinschaft (DFG), dem Bundesinstitut für Bildung und Forschung (BMBF), der EU, dem National Institute of Mental Health (NIMH), der Kröner-Fresenius-Stifung und Abide Pharmaceutics, Inc. Ewgeni Jakubovski wird gefördert durch das BMBF., (© Georg Thieme Verlag KG Stuttgart · New York.)

Pre- and perinatal complications have been implicated in the onset and clinical expression of Tourette syndrome albeit with considerable inconsistencies across studies. Also, little is known about their role in co-occurring obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in individuals with a tic disorder. Therefore, we aimed to investigate the role of pre- and perinatal complications in relation to the presence and symptom severity of chronic tic disorder and co-occurring OCD and ADHD using data of 1113 participants from the Tourette International Collaborative Genetics study. This study included 586 participants with a chronic tic disorder and 527 unaffected family controls. We controlled for age and sex differences by creating propensity score matched subsamples for both case-control and within-case analyses. We found that premature birth (OR = 1.72) and morning sickness requiring medical attention (OR = 2.57) were associated with the presence of a chronic tic disorder. Also, the total number of pre- and perinatal complications was higher in those with a tic disorder (OR = 1.07). Furthermore, neonatal complications were related to the presence (OR = 1.46) and severity (b = 2.27) of co-occurring OCD and also to ADHD severity (b = 1.09). Delivery complications were only related to co-occurring OCD (OR = 1.49). We conclude that early exposure to adverse situations during pregnancy is related to the presence of chronic tic disorders. Exposure at a later stage, at birth or during the first weeks of life, appears to be associated with co-occurring OCD and ADHD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: We assessed the role of prenatal maternal smoking in risk for Tourette syndrome and chronic tic disorder (TS/CT) and pediatric-onset obsessive-compulsive disorder (OCD)., Method: In an analysis of 73,073 singleton pregnancies from the Danish National Birth Cohort, we calculated incidence rates (IR) per 1,000 person-year for TS/CT and OCD. We then determined crude and adjusted hazard ratios and 95% CIs associated with prenatal maternal smoking, considering smoking as a dichotomous (yes/no) variable or a stratified variable (no smoking, light smoking, and heavy smoking [≥10 cigarettes/day]). Additional analyses examined the effect of maternal smoking on risk for TS/CT with other comorbid psychiatric conditions., Results: In final adjusted analyses, heavy smoking was associated with a 66% increased risk for TS/CT (adjusted hazard ratio = 1.66, 95% CI = 1.17-2.35). In addition, heavy smoking was associated with a 2-fold increased risk for TS/CT with comorbid attention-deficit/hyperactivity disorder (ADHD), and both light and heavy smoking were associated with a more than 2-fold increased risk for TS/CT with any non-ADHD psychiatric comorbidity. Our parallel analyses of pediatric-onset OCD were likely underpowered but showed similar relationships., Conclusion: Prenatal maternal smoking was associated with increased risk for TS/CT as well as TS/CT with comorbid psychiatric conditions, even after adjustment for several important variables, including maternal psychiatric history, socioeconomic status, and partner smoking. Our findings point to a pathway linking prenatal tobacco exposure and altered brain development to TS/CT., (Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Tic disorders (TD), including chronic/persistent TD (CTD) and Tourette syndrome, have been described and studied for many years. Within the last two decades, intensified study efforts led to more specific assumptions about genesis and influences of both hereditary and environmental factors. TD in children and adolescents are very often accompanied by attention-deficit/hyperactivity disorders and obsessive-compulsive disorders (OCD) as comorbid disorders. Comorbidities are aggravating factors concerning prognosis and treatment opportunities. Therefore, etiological considerations and treatment strategies have to take associated psychiatric disorders into account. Treatment approaches are symptom targeted and include behavioral treatments and/or medication and show positive outcomes concerning tic symptomatology, global functioning, and associated psychopathology. This review presents an update of the research, definitions, and classification according to ICD-10 and DSM-5 and summarizes the diagnostic procedures and most effective clinical strategies., (Georg Thieme Verlag KG Stuttgart · New York.)

Gilles de la Tourette's syndrome (GTS) is a disorder in which obsessive-compulsive (OC), Attention Deficit Hyperactivity Disorder (ADHD) and autism symptoms occur in up to 60% of patients, suggesting shared etiology. We explored the phenotypic structure of tic, OC, ADHD, and autism symptoms as measured by the YGTSS,Y-BOCS,CAARS and AQ, in 225 GTS patients and 371 family members. First, Confirmatory Factor Analyses (CFA) were performed on the symptom structure of each separate symptom scale. Second, the symptom dimensions derived from each scale were combined in one model, and correlations between them were calculated. Using the correlation matrix, Exploratory Factor Analyses (EFA) were performed on the symptom dimensions across the scales. EFA revealed a five factor structure: tic/aggression/symmetry; OC symptoms/compulsive tics/ numbers and patterns; ADHD symptoms; autism symptoms; and hoarding/inattention symptoms. The results are partly in line with the traditional categorical boundaries of the symptom scales used, and partly reveal a symptom structure that cuts through the diagnostic categories. This phenotypic structure might more closely reflect underlying etiologies than a structure that classically describes GTS patients according to absence or presence of comorbid OCD, ADHD and autism, and might inform both future genetic and treatment studies., Competing Interests: The authors have no conflicts of interest., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

This is the first nationwide register-based study to examine the relationship between prenatal maternal smoking and Tourette syndrome. A total of 767 children diagnosed with Tourette syndrome were identified from the Finnish Hospital Discharge Register. Each case was matched to four controls. Information on maternal smoking during pregnancy was obtained from the Finnish Medical Birth Register. Conditional logistic regression models were used for statistical analyses. Prenatal maternal smoking was associated with Tourette syndrome when comorbid with ADHD (OR 4.0, 95 % CI 1.2-13.5, p = 0.027 for exposure during first trimester, OR 1.7, 95 % CI, 1.05-2.7, p = 0.031 for exposure for the whole pregnancy). There was no association between maternal smoking during pregnancy and Tourette syndrome without comorbid ADHD (OR 0.5, 95 % CI 0.2-1.3, p = 0.166, OR 0.9, 95 % CI 0.7-1.3, p = 0.567). Further research is needed to elucidate the mechanisms behind the association between prenatal maternal smoking and Tourette syndrome with comorbid ADHD.

Tourette syndrome (TS) is a childhood-onset tic disorder associated with abnormal development of brain networks involved in the sensory and motor processing. An involvement of immune mechanisms in its pathophysiology has been proposed. Animal models based on active immunization with bacterial or viral mimics, direct injection of cytokines or patients' serum anti-neuronal antibodies, and transgenic approaches replicated stereotyped behaviors observed in human TS. A crucial role of microglia in the neural-immune crosstalk within TS and related disorders has been proposed by animal models and confirmed by recent post mortem studies. With analogy to autism, genetic and early life environmental factors could foster the involvement of immune mechanisms to the abnormal developmental trajectories postulated in TS, as well as lead to systemic immune dysregulation in this condition. Clinical studies demonstrate an association between TS and immune responses to pathogens like group A Streptococcus (GAS), although their role as risk-modifiers is still undefined. Overactivity of immune responses at a systemic level is suggested by clinical studies exploring cytokine and immunoglobulin levels, immune cell subpopulations, and gene expression profiling of peripheral lymphocytes. The involvement of autoantibodies, on the other hand, remains uncertain and warrants more work using live cell-based approaches. Overall, a body of evidence supports the hypothesis that disease mechanisms in TS, like other neurodevelopmental illnesses (e.g. autism), may involve dysfunctional neural-immune cross-talk, ultimately leading to altered maturation of brain pathways controlling different behavioral domains and, possibly, differences in organising immune and stress responses. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Genetic factors are important in the pathogenesis of Tourette syndrome (TS). Notably, Dopamine receptor D2 (DRD2) gene has been suggested as a possible candidate gene for this disorder. Several studies have demonstrated that DRD2/ANKK1 TaqIA polymorphism is associated with an increased risk of developing TS. However, past results remain conflicting. We addressed this controversy by performing a meta-analysis of the relationship between DRD2/ANKK1 TaqIA polymorphism and TS., Methods: Literature was searched in multiple databases including PUBMED, COCHRANE and WEB OF SCIENCE up to July 2014. The number of the genotypes for DRD2/ANKK1 TaqIA in the TS and control subjects was extracted and statistical analysis was performed using Review Manager 5.0.16 and Stata 12.0 software. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) were utilized to calculate the risk of TS with DRD2/ANKK1 TaqIA. Stratified analysis based on ethnicity was also conducted., Results: 523 patients with TS, 564 controls and 87 probands plus 152 relatives from five published studies were finally involved in this meta-analysis. Combined analysis revealed that the overall ORs for the DRD2/ANKK1 TaqIA A1 allele were 1.69 (95%CIs = 1.42-2.00) in the fixed-effect model and 1.66 (95%CIs = 1.33-2.08) in the random-effects model. Stratification by ethnicity indicated the TaqIA A1 allele was significantly associated with TS in Caucasians (fixed-effect model: OR=1.75, 95%CI = 1.43-2.16; random-effect model: OR=1.69, 95%CI = 1.25-2.28) and in Asians (OR=1.54, 95%CI = 1.12-2.10). Meta-analysis of the A1A1 vs. A2A2 (homozygous model), A1A2 vs. A2A2 (heterozygous model) and A1A1+A1A2 vs. A2A2 (dominant model) of this polymorphism revealed a significant association with TS in overall populations and Caucasians., Conclusions: This meta-analysis suggested that the DRD2/ANKK1 TaqIA polymorphism might contribute to TS susceptibility, especially in Caucasian population. However, further investigation with a larger number of worldwide studies should be conducted to verify the association.

Objective: In a nationwide prospective cohort study, we examined the possible association between maternal autoimmune disease (AD) and later diagnosis of Tourette syndrome (TS) in offspring., Method: Data from national Danish health registers identified a cohort consisting of all children born in Denmark between 1990 and 2007 (n = 1,116,255), followed prospectively from birth until 2011, date of TS diagnosis, death, or emigration/disappearance, whichever came first. The incidence rate ratio (IRR) of TS, dependent on whether or not the mother had a prior diagnosis of AD, was estimated by Poisson regression with 95% CIs and adjusted for age, calendar time, place of birth, maternal and paternal age, parental psychiatric diagnoses other than TS, and parental TS., Results: The cohort contributed a total of 13,000,162 person years and 2,442 participants with a diagnosis of TS (414 females and 2,028 males). Prior maternal AD was found in 110 of the 2,442 children with TS, corresponding to an increased risk of TS, with an adjusted IRR of 1.22 (95% CI = 1.01-1.48). Maternal history of a prior AD increased the risk of TS in males, with an adjusted IRR of 1.29 (95% CI = 1.05-1.58), but not in females, with an adjusted IRR of 0.89 (95% CI = 0.52-1.52)., Conclusion: Maternal AD was associated with a 29% increased incidence rate of TS in male offspring. This finding supports the hypothesis that neuroimmunological disorders may act as a component in the etiology of a subset of TS., (Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Tourette syndrome (TS) is a complex, heterozygous genetic disorder. The number of molecular genetic studies have investigated several candidate genes, particularly those implicated in the dopamine system. The dopamine D3 receptor (DRD3) gene has been considered as a candidate gene in TS. There was not any report about the association study of TS and DRD3 gene in Han Chinese population. We combined a case-control genetic association analysis and nuclear pedigrees transmission disequilibrium test (TDT) analysis to investigate the association between DRD3 gene rs6280 single nucleotide polymorphisms (SNPs) and TS in a Han Chinese population., Methods: A total of 160 TS patients was diagnosed by the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The DRD3 gene rs6280 SNPs were genotyped by TaqMan SNP genotyping assay technique in all subjects. We used a case-control genetic association analysis to compare the difference in genotype and allele frequencies between 160 TS patients and 90 healthy controls. At the same time, we used TDT analysis to identify the DRD3 gene rs6280 transmission disequilibrium among 101 nuclear pedigrees., Results: The genotype and allele frequency of DRD3 gene rs6280 SNPs had no statistical difference between control group (90) and TS group (160) (χ2 = 3.647, P = 0.161; χ2 = 0.643, P = 0.423) using Chi-squared test. At the basis of the 101 nuclear pedigrees, TDT analysis showed no transmission disequilibrium of DRD3 gene rs6280 SNPs (χ2 = 0; P = 1)., Conclusions: Our findings provide no evidence for an association between DRD3 gene rs6280 and TS in the Han Chinese population.

Unlabelled: Attention deficit hyperactivity disorder (ADHD) is the most common comorbid condition in patients with Tourette syndrome (TS). The co-occurrence of ADHD and TS is in most cases associated with a higher social and psychopathological impairment. Comorbidity between Tourette and ADHD appears to have a complex and partially known pathogenesis in which genetic, environmental, and neurobiological factors can be implicated. Genetic studies have revealed an involvement of dopaminergic, catecholaminergic, and GABAergic genes that modulated the activity of neurotransmitters. Furthermore, there are a lot of networks implicated in the development of ADHD and TS, involving cortical and striatal areas and basal ganglia. Although a large number of studies tried to find a common pathogenesis, the complex pathways responsible are not clear. The genes implicated in both disorders are currently unidentified, but it is probable that epigenetic factors associated with neural modifications can represent a substrate for the development of the diseases., Conclusion: In this paper, recent advances in neurobiology of ADHD and TS are reviewed, providing a basis for understanding the complex common pathogenesis underlying the frequent co-occurrence of the two conditions and the therapeutic choices.

There has been a persistent attempt to explain Mozart's talent as connected to physical and mental illness. While Mozart's musical compositions and performances were often acclaimed for their "taste," the composer's personal behavior sometimes astonished those who witnessed "blödeln" or wild horseplay, practical joking, and scatological humor. Most recently, Mozart's eccentric behavior has been attributed to Gilles de la Tourette syndrome. This chapter investigates the evidence for these retrospective diagnoses and reassesses this evidence by paying particular attention to the milieu in which Mozart lived. We argue that Mozart's putative pathological behavior was a manifestation of his resilience in face of multiple adversities and was deeply rooted in his sense of play. Our hypothesis is that play, rather than neuropsychiatric disease, was essential to the operation of his genius., (© 2015 Elsevier B.V. All rights reserved.)

After having examined the definition, clinical phenomenology, comorbidity, psychopathology, and phenotypes in the first paper of this Series, here I discuss the assessment, including neuropsychology, and the effects of Gilles de la Tourette syndrome with studies showing that the quality of life of patients with Tourette's syndrome is reduced and that there is a substantial burden on the family. In this paper, I review my local and collaborative studies investigating causal factors (including genetic vulnerability, prenatal and perinatal difficulties, and neuro-immunological factors). I also present my studies on neuro-imaging, electro-encephalograms, and other special investigations, which are helpful in their own right or to exclude other conditions. Finally, I also review our studies on treatment including medications, transcranial magnetic stimulation, biofeedback, target-specific botulinum toxin injections, biofeedback and, in severe refractory adults, psychosurgery and deep brain stimulation. This Review summarises and highlights selected main findings from my clinic (initially The National Hospital for Neurology and Neurosurgery Queen Square and University College London, UK, and, subsequently, at St George's Hospital, London, UK), and several collaborations since 1980. As in Part 1 of this Series, I address the main controversies in the fields and the research of other groups, and I make suggestions for future research., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Febrile convulsion (FC) and Tourette syndrome (TS) are both common neurological disorders in infants and children. Both disorders share clinical similarities, such as paroxysmal symptoms with normal neurodevelopment and expected remission over time. This population-based study investigated the association between FC with TS during childhood neurodevelopment., Method: We used the Taiwan National Health Insurance Research Database to conduct a retrospective cohort analysis on 1586 FC patients. A reference cohort of 6344 non-FC patients, matched for age, sex, urbanization level, parental occupation, and index year, was used for comparison. The risk of the occurrence of TS in FC patients was assessed using a Cox proportional hazard regression model., Results: The overall incidence of TS was higher in the FC cohort than in the non-FC cohort (28.5 vs 13.9 per 10,000 person-years; adjusted hazard ratio=1.91, 95% confidence interval=1.32-2.75). The associated risk factors for FC patients to develop TS were boys, children living in rural areas, and children whose parents held blue-collar positions. Moreover, the risk of TS in FC patients rose from 0.89 to 16.0 (trend test P<0.0001) when the frequency of FC-related medical visits increased from 1 to 2 times to more than 4 times. The adjusted hazard ratio for TS in related to FC-related medical visits was 1.02 (95% CI=1.02-1.03) per one frequency increment., Conclusion: FC may increase the risk of subsequent TS occurrence in children. Children who had frequent medical visits for FC were particularly vulnerable., (Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: Infections resulting in immune activation have been proposed to play an etiological role in a subgroup of patients with Tourette syndrome (TS)., Methods: In order to further characterize the interaction between pathogens and the innate immune system the toll-like receptor (TLR) 4 on CD14 + monocytes and soluble CD14 (sCD14) levels were analyzed in the serum of 33 Tourette patients and 31 healthy controls. Moreover, collected blood samples were stimulated with lipopolysaccharide (LPS) mimicking a bacterial infection. TLR4 was analysed by flow cytometry, sCD14 was analysed by enzyme-linked immunosorbent assay., Results: Patients had a lower receptor expression of TLR4 after stimulation with LPS (P = 0.045) and higher levels of sCD14 (unstimulated P = 0.014, after LPS P = 0.045). The increase in TLR4 expression after stimulation with LPS was significantly higher in the control group (P = 0.041)., Conclusions: Higher levels of sCD14, lower levels of TLR4 expression after stimulation and a diminished up-regulation of TLR4 expression after LPS stimulation in patients might represent an impaired activation of the innate immune response in TS, especially in regard to bacterial infection. The impaired response to pathogens could eventually lead to a higher susceptibility for infections. Recurring infections and a chronic inflammation could trigger and maintain the symptoms of TS.

Traumatic head injury is a very rare cause of secondary tic disorders. We add another case by describing, for the first time, the response to tetrabenazine in a blinded video assessment. Our patient had a severe traumatic head injury and subsequently developed tics refractory to various agents including neuroleptics. We assessed tetrabenazine treatment by virtue of patient's impression, the treating neurologist's non-blinded (Yale Global Tic Severity Scale) and a second neurologist's blinded assessment (modified Rush Video Scale). The Yale Global Tic Severity Score improved by 24% on 12.5 mg twice daily and 45% on 12.5 mg thrice daily. Subjective improvement was 50% and 70%, respectively. The modified Rush Video scores improved by 21% and 28.5%, respectively. Post-traumatic tourettism can respond to tetrabenazine. The magnitude of benefit though, may be overestimated with open-label observations, thus there is a need for studies examining objectively the effect of tetrabenazine in tic disorders.

Tourette's syndrome (TS) is a neurodevelopmental disorder characterised by recurring motor and phonic tics. The pathogenesis of TS is considered to reflect dysregulations in the signalling of dopamine (DA) and other neurotransmitters, which lead to excitation/inhibition imbalances in cortico-striato-thalamocortical circuits. The causes of these deficits may reflect complex gene × environment × sex (G × E × S) interactions; indeed, the disorder is markedly predominant in males, with a male-to-female prevalence ratio of approximately 4 : 1. Converging lines of evidence point to neuroactive steroids as being likely molecular candidates to account for G × E × S interactions in TS. Building on these premises, our group has begun examining the possibility that alterations in the steroid biosynthetic process may be directly implicated in TS pathophysiology; in particular, our research has focused on 5α-reductase (5αR), the enzyme catalysing the key rate-limiting step in the synthesis of pregnane and androstane neurosteroids. In clinical and preclinical studies, we found that 5αR inhibitors exerted marked anti-DAergic and tic-suppressing properties, suggesting a central role for this enzyme in TS pathogenesis. Based on these data, we hypothesise that enhancements in 5αR activity in early developmental stages may lead to an inappropriate activation of the 'backdoor' pathway for androgen synthesis from adrenarche until the end of puberty. We predict that the ensuing imbalances in steroid homeostasis may impair the signalling of DA and other neurotransmitters, ultimately resulting in the facilitation of tics and other behavioural abnormalities in TS., (© 2013 British Society for Neuroendocrinology.)

Background: Tourette's syndrome is a developmental neuropsychiatric disorder characterized by multiple motor, stereotypical but non-rhythmic movements and vocalizations/phonics called tics. It is one of several disorders that have tics as their cardinal feature. These tics manifest themselves in various ways, ranging from simple eye blinking to coprolalia (involuntary swearing)., Method: We conducted a review in Medline and ScienceDirect without restrictions, after which we did a normative and qualitative analysis to identify relevant information to improve the profession's understanding of the syndrome, including its pathophysiology., Results: This disorder is much more common than once believed, and may interfere with patients' social relationships and occupational functions. The development of new treatments is important to achieve more effective management with fewer side effects. Animal models of Tourette's syndrome would help foster understanding the pathophysiology and pharmacological treatment of tic symptoms., Conclusions: Although significant advances have been made, research in the field is crucial to clarify further the physiological aspects of the syndrome.

Competing theories on the etiology and treatment of chronic tic disorders and Tourette syndrome have long made the search for efficacious intervention more challenging for patients and families seeking to reduce functional impairment related to tic symptoms. These symptoms were historically posited to be either psychological in origin, leading to the long tradition of psychoanalytic psychotherapy for tics, or biological in nature, particularly since the advent of successful treatments using neuroleptic medications. Current thinking about the phenomenology of tic disorders comes from growing empirical evidence as well as advances in neuroscience and genetics research and reveals a biological vulnerability that is exacerbated by physiological arousal related to environmental or interpersonal stress. This manuscript summarizes the evolution of this knowledge base and describes current best-practice recommendations for patients, families, and clinicians., (© 2013 New York Academy of Sciences.)

Objective: This study aimed to investigate comorbidity, and sociodemographic and clinical characteristics in children and adolescents with Tourette's syndrome (TS) and chronic motor or vocal tic disorder (CMVTD), and to determine the predictors of tic disorders., Materials and Methods: In all, 57 children and adolescents with TS and CMVTD were compared with a control group. Data were obtained using the Yale Global Tic Severity Scale (YGTSS), Turgay DSM-IV-Based Disruptive Behavioral Disorders Screening and Rating Scale (T-DSM-IV-S), Children's Depression Inventory (CDI), Screen for Child Anxiety-Related Disorders (SCARED), Maudsley Obsessive-Compulsive Inventory (MOCI), and Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL)., Results: Mean age of the patients was 10.5 ± 2.4 years. In all, 56 (98.2%) of the patients had simple motor tics, 50 (87.7%) had complex motor tics, and 43 (75.4%) had vocal tics. Self-injurious behavior was observed in 24 (42.1%) patients. In total, 46 (80.7%) of the patients had ≥1 comorbid disorder. Among the observed comorbid disorders, attention deficit-hyperactivity disorder (ADHD) was the most common (observed in 40.4% of the patients), followed by obsessive-compulsive disorder (OCD) (19.3%). A higher-level of maternal education and absence of ADHD were associated with a reduction in the risk of a tic disorder. A family history of psychiatric disorder increased the risk of a tic disorder 5.61-fold, and nail biting increased the risk of a tic disorder 8.2-fold. Every 1-unit increase in CDI score increased the risk of a tic disorder by 12%., Conclusion: Chronic tic disorders (CTDs) are often accompanied by other psychiatric disorders. Both child- and family-related factors are associated with the risk of developing a tic disorder. Determination of both the protective and risk factors would be beneficial for improving the mental health of the general public.

Almost since the beginning of research on Tourette syndrome (TS), tics have been linked to a dysfunction of the dopamine (DA) system. At first, this assumption was mainly based on clinical findings of DA antagonists being the most effective drug in treating tics, but in recent years nuclear imaging has enabled a much deeper understanding of DA neurotransmission in TS. Based on the findings of various PET and SPECT studies the first part of the review discusses four hypotheses on DA dysfunctions in TS: (i) DA hyperinnervation, (ii) supersensitive DA receptors, (iii) pre-synaptic DA abnormality and (iv) DA tonic-phasic dysfunction. According to the latter hypothesis, reduced levels of tonic DA in the extracellular space lead to higher concentrations of DA in the axon terminal and an increase of stimulus-dependent DA release. The second part of the review addresses the modulating role of DA in some major clinical features of TS, like the exacerbation with stress or infection and the association with deficient sensorimotor gating., (Copyright © 2012. Published by Elsevier Ltd.)

An autoimmune diathesis has been proposed in Tourette syndrome (TS) and related neuropsychiatric disorders such as obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism and anorexia nervosa. Environmental triggers including infection and xenobiotics are hypothesized to lead to the production of brain-directed autoantibodies in a subset of genetically susceptible individuals. Although much work has focused on Group A Streptococcus (GAS), the role of this common childhood infection remains controversial. Animal model studies based on immune and autoantibody findings in TS have demonstrated immunoglobulin (Ig) deposits and stereotypic movements and related behavioral disturbances reminiscent of TS following exposure to GAS, other activators of host anti-microbial responses, soluble immune mediators and anti-GAS or anti-neuronal antibodies. Demonstration of the ability to recreate these abnormalities through passive transfer of serum IgG from GAS-immunized mice into naïve mice and abrogation of this activity through depletion of IgG has provided compelling evidence in support of the autoimmune hypothesis. Immunologically-based animal models of TS are a potent tool for dissecting the pathogenesis of this serious neuropsychiatric syndrome., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Environmental exposures during the prenatal period, perinatal stages, and postnatal life may contribute to onset and course of Tourette syndrome (TS). Pregnancy-related noxious exposures may be more frequent in pregnancies of children who will develop TS, particularly maternal smoking and prenatal life stressors. Lower birth weight and use of forceps at delivery may be associated with tic severity in the offspring; moreover, low birth weight and maternal smoking during pregnancy may affect the risk of co-morbid attention-deficit/hyperactivity and obsessive-compulsive disorders. Group A streptococcal infections as risk-modifier for TS has not been convincingly demonstrated to date, although an interaction with stressors was suggested. The PANDAS hypothesis is currently undergoing a nosological revision. Only limited anecdotal evidence supports a link of TS to other pathogens. Nevertheless, the relationship between infections and TS may be complex. Recent data point to intrinsically altered immune regulation in TS, which might predispose to both infections and autoimmune mechanisms; however, evidence of cell-mediated and antibody-mediated autoimmunity in TS is still insufficient. Psychosocial stress remains the most important contextual factor influencing tic severity, as confirmed by prospective studies. This might in part be related to enhanced reactivity of the stress response in TS patients, the mechanisms of which need to be explored further. New studies on large prospective cohorts of patients of different age and the identification of reliable biomarkers or endophenotypes indicating early, prenatal exposure to environmental insults are needed., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In the present manuscript we review a substantial body of literature describing several pre-clinical animal models designed and developed with the purpose of investigating the biological determinants of Tourette syndrome (TS). In order to map the animal models onto the theoretical background upon which they have been devised, we first define phenomenological and etiological aspects of TS and then match this information to the available pre-clinical models. Thus, we first describe the characteristic symptoms exhibited by TS patients and then a series of hypotheses attempting to identify the multifactorial causes of TS. With respect to the former, we detail the phenomenology of abnormal repetitive behaviors (tics and stereotypies), obsessive-compulsive behaviors and aberrant sensory-motor gating. With respect to the latter, we describe both potential candidate vulnerability genes and environmental factors (difficult pregnancies, psychosocial stressors and infections). We then discuss how this evidence has been translated in pre-clinical research with respect to both dependent (symptoms) and independent (etiological factors) variables. Thus, while, on the one hand, we detail the methodologies adopted to measure abnormal repetitive and obsessive-compulsive behaviors, and sensory-motor gating, on the other hand, we describe genetic engineering studies and environmental modulations aimed at reproducing the proposed biological determinants in laboratory rodents. A special emphasis is placed upon "programming" events, occurring during critical stages of early development and exerting organizational delayed consequences. In the final section, we outline a heuristic model with the purpose of integrating clinical and pre-clinical evidence in the study of TS., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Gilles de la Tourette Syndrome (TS) is a neuropsychiatric disorder that is caused by a likely complex genetic basis, interacting with environmental factors. Just as multiple large scale collaborative projects for TS are starting out and the first ever genomewide association study for TS has been published, this review provides a synthetic overview of more than two decades of active research. Studies of the dopaminergic and serotonergic pathways, have yielded inconsistent results, although, for instance, the involvement of DRD2, MAO-A, and DAT1 has been supported by independent findings. The study of chromosomal aberrations in TS etiology has implicated multiple genes, with SLITRK1 being the most prominent example. Common underlying themes with other neurodevelopmental disorders are emerging and attention on neurexins, neuroligins, and genes from the histaminergic and glutamatergic pathways is increased. Propelled by the gradual availability of large scale TS cohorts, and novel methodologies for the study of both common and rare genetic variants, the new era of TS genetics holds the promise to identify novel targets for improved therapies., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Tourette syndrome (TS) is often accompanied by other symptoms and syndromes. The two best-known co-morbidities are Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD), but also other conditions like rage-attacks, depression, and sleeping disturbances are frequent in persons with TS. Both in clinical cohorts and in population-based cohorts the prevalence of co-morbidities is high. The presence of co-morbid ADHD and/or OCD has an impact on psychosocial, educational, and neuropsychological consequences of TS and it is associated with higher rates of other co-morbid disorders, like rage, anxiety, and conduct disorders. The symptoms of a co-morbid disorder might appear prior to the time that tics reach clinical attention. The TS phenotype probably changes during the course of the disease. The exact aetiology of the co-occurrence of co-morbid disorders and TS is not known, but they probably all are neurotransmitter disorders. European guidelines recommend first-choice pharmacological treatment, but randomised double-blinded trials are needed. Professionals need to be aware of the close relationship between TS and co-morbidities in order to give the patients the right treatment and support.

Tourette Syndrome (TS) is a neurological disorder characterized by motor and phonic tics affecting approximately 1% of the pediatric population. Behavioral comorbidities often include obsessive-compulsive behavior and impaired attention. The neurobiological substrates associated with TS generally entail abnormalities in neurotransmitter circuitry regulating basal ganglia activity. The neurotransmitters most often associated with TS are dopamine, serotonin, and GABA. TS origin roots in genetic predisposing factors, and environmental variables favoring tic onset and exacerbation. Among the latter, repeated infections with group A beta-hemolytic Streptococcus and psychosocial stressors encountered during development have been proposed to constitute likely susceptibility factors. In this chapter, we describe how this clinical/epidemiological knowledge has been translated into animal models of TS. Specifically, we review several studies attempting to reproduce TS-like symptoms (tics and behavioral stereotypies) and comorbidities (impaired attention, increased locomotion, and perseverative responding) in laboratory rodents. Additionally, we discuss studies in which the genetic and environmental predisposing factors have been modeled in experimental subjects. Ultimately, we propose a unifying perspective recapitulating dependent and independent variables in the preclinical study of TS and discuss its potential theoretical and heuristic implications., (© 2013 Elsevier Inc. All rights reserved.)

Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400 kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.

Tourette syndrome (TS) is a neurological condition first described by Georges Gilles de la Tourette in 1885. TS was largely thought of as a rare and bizarre condition until the 1960s, when the beneficial effects of neuroleptics on tic symptoms led to an exponential increase in neuroscientific research. Today TS is known to be a relatively common condition that is frequently misdiagnosed due to a combination of its variable manifestation and the waxing and waning of tic frequency and severity. Although there has been a paucity of research on TS compared to other movement disorders, in recent years TS has garnered increasing interest and has shown a number of novel and complex sides, about which much is yet to be learnt. The present article discusses where research has taken us thus far and where it is heading in all the major facets of this fascinating condition.

Objective: To identify the risk factors for Tourette syndrome (TS) in children., Methods: Through a genetic epidemiologic case control study, segregation ratio was estimated using the method of Li-Manted-Gart in 80 children with TS. Heritability for the first- and second-degree relatives was estimated using the Falconer regression method. In addition, the 80 children and 80 controls with other diseases were evaluated using the Family Environment Scale and a self-designed questionnaire. Risk factors for TS were investigated using single factor and multifactor regression analysis., Results: The segregation ratio of TS was 0.1176. Heritabilities for the first- and second-degree relatives were (49.7±2.6)% and (21.5±3.4)% respectively. The weighted mean heritability of the first-degree and second-degree relatives was (39.5±2.1)%. Significantly decreased scores were noted in independence, active-recreational orientation and organization and increased scores were noted in the conflict and control in the TS group compared with the control group (P<0.01). Single factor analysis indicated that the risk factors for TS included family history, type of home education, maternal smoking, family conflict, low level of parental education, family control and fetal anoxia. Multifactor regression analysis indicated that there were five important risk factors for TS: family history, family conflict, type of family education, low level of parental education and maternal smoking., Conclusions: Both heredity and environment are involved in the pathogenesis of TS. The mode of inheritance for TS is polygenic. Improving the living environments of children with a family history of TS is of prime importance.

Tourette's syndrome is a neurodevelopmental disorder clinically characterized by multiple motor and phonic tics. It is likely that a neurobiological susceptibility to the disorder is established during development by the interaction of genetic, biochemical, immunological, and environmental factors. This study sought to investigate the possible correlation of several immunological and biochemical markers with Tourette's syndrome. Children with Tourette's syndrome attending a tertiary pediatric medical center from May 2008 to April 2010, and healthy age-matched control subjects underwent a comprehensive biochemical and immunological work-up. Demographic data were abstracted from the medical records. Findings were compared between the groups and analyzed statistically. Sixty-eight children with Tourette's syndrome (58 males, 85.3%) and 36 healthy children (25 males, 69.4%) were recruited. Compared with the control group, the Tourette's syndrome group had significantly higher levels of ferritin (p = 0.01) and hemoglobin (p = 0.02), a lower level of zinc (p = 0.05), and a lower percentage of non-ceruloplasmin copper (p = 0.01). Analysis of the immunological markers revealed no significant between-group differences in IgA, IgM or IgG; however, IgE and IgG-4 levels were significantly higher in the Tourette's syndrome group (p = 0.04 and p = 0.02, respectively). Children with Tourette's syndrome have high levels of biochemical indices of oxidative stress and the quantitative immunoglobulins. These findings add to the still-limited knowledge on the pathogenesis of Tourette's syndrome and may have implications for the development of novel therapeutic modalities., (© Springer-Verlag 2011)

Knowledge about the aetiology of Gilles de la Tourette syndrome (GTS) is very limited. GTS has a complex mode of inheritance in which both genetic and environmental factors are believed to be involved in disease development. Different approaches to identify GTS associated genes have led to the discovery of several candidate genes. However, none of these has been shown to be major causative genes associated with the development of GTS. Future use of large clinical cohorts and new technologies will hopefully result in the identification of genes associated with GTS.

Tourette syndrome (TS) is a common, chronic neuropsychiatric disorder characterized by the presence of fluctuating motor and phonic tics. The typical age of onset is ∼5-7 years, and the majority of children improve by their late teens or early adulthood. Affected individuals are at increased risk for the development of various comorbid conditions, such as obsessive-compulsive disorder, attention deficit hyperactivity disorder, school problems, depression, and anxiety. There is no cure for tics, and symptomatic therapy includes behavioral and pharmacological approaches. Evidence supports TS being an inherited disorder; however, the precise genetic abnormality remains unknown. Pathologic involvement of cortico-striatal-thalamo-cortical (CSTC) pathways is supported by neurophysiological, brain imaging, and postmortem studies, but results are often confounded by small numbers, age differences, severity of symptoms, comorbidity, use of pharmacotherapy, and other factors. The primary site of abnormality remains controversial. Although numerous neurotransmitters participate in the transmission of messages through CSTC circuits, a dopaminergic dysfunction is considered a leading candidate. Several animal models have been used to study behaviors similar to tics as well as to pursue potential pathophysiological deficits. TS is a complex disorder with features overlapping a variety of scientific fields. Despite description of this syndrome in the late 19th century, there remain numerous unanswered neurobiological questions.

Tourette syndrome is a common childhood-onset neurobehavioral disorder characterized by multiple motor and phonic tics affecting boys more frequently than girls. Premonitory sensory urges prior to tic execution are common, and this phenomenon helps to distinguish tics from other hyperkinetic movement disorders. Tourette syndrome is commonly associated with attention deficit hyperactivity disorder, obsessive-compulsive disorder, learning difficulties, and impulse control disorder. The pathophysiology of this complex disorder is not well understood. Involvement of basal ganglia-related circuits and dopaminergic system has been suggested by various imaging and postmortem studies. Although it is considered a genetic disorder, possibly modified by environmental factors, an intense search has thus far failed to find causative genes. Symptomatic treatment of tics chiefly utilizes various alpha adrenergic agonists, antidopaminergic drugs, topiramate, botulinum toxin, and deep brain stimulation. Habit reversal therapy and other behavioral approaches may be a reasonable option for some cases. Improved understanding of Tourette syndrome should lead to better symptomatic and more effective pathogenesis-targeted therapies., (Copyright © 2011 Movement Disorder Society.)

Tourette syndrome is a chronic motor and vocal tic disorder, which is common (1%). The aetiology is complex (mostly genetic) and 90% of people have co-morbid psychiatric disorders and reduced quality of life. Management includes reassurance, education, behavioural treatments and medications for tics and psychopathology.

Tic disorders, including Tourette syndrome, are an intriguing group of paroxysmal movement abnormalities that begin in childhood, have a fluctuating course, are capable of causing psychosocial and physical problems, and often improve by early adulthood. These disorders are frequently associated with a variety of comorbid problems whose negative effects may exceed those of tics. Therapy is strictly symptomatic and usually includes educational, behavioral, and a variety of pharmacological therapies. Although there is strong evidence supporting an inherited basis, the precise genetic abnormality remains unknown. A proposed poststreptococcal autoimmune etiology remains controversial. Pathophysiologically, tics appear to arise from an alteration within cortico-striatal-thalamo-cortical circuits, but the definitive site is unknown. Evidence supports an abnormality of synaptic neurotransmission, likely involving the dopaminergic system., (Copyright © 2011 Elsevier B.V. All rights reserved.)