European clinical guidelines for Tourette syndrome and other tic disorders:summary statement

In 2011 a working group of the European Society for the Study of Tourette syndrome (ESSTS) developed the first European Guidelines for Tourette syndrome (TS) published in the ECAP journal. After a decade ESSTS now presents updated guidelines, divided into four sections: Part I: assessment, Part II: psychological interventions, Part III: pharmacological treatment and Part IV: deep brain stimulation (DBS). In this paper, we summarise new developments described in the guidelines with respect to assessment and treatment of tics. Further, summary findings from a recent survey conducted amongst TS experts on these same topics are presented, as well as the first European patient representative statement on research. Finally, an updated decision tree is introduced providing a practical algorithm for the treatment of patients with TS. Interestingly, in the last decade there has been a significant shift in assessment and treatment of tics, with more emphasis on non-pharmacological treatments

Vitamin D levels in children and adolescents with chronic tic disorders: a multicentre study

This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3-16 years) with CTD (n = 327); first-degree relatives (3-10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (n = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (n = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27-3.42, p < 0.01). There was no association between 25(OH)D and tic severity. However, a 10 ng/ml increase in 25(OH)D was associated with lower odds of having comorbid ADHD within the CTD cohort (OR 0.55, 95% CI 0.36-0.84, p = 0.01) and was inversely associated with ADHD symptom severity (β = - 2.52, 95% CI - 4.16-0.88, p < 0.01). In conclusion, lower vitamin D levels were not associated with a higher presence or severity of tics but were associated with the presence and severity of comorbid ADHD in children and adolescents with CTD

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part II: psychological interventions

Part II of the European clinical guidelines for Tourette syndrome and other tic disorders (ECAP journal, 2011) provides updated information and recommendations for psychological interventions for individuals with tic disorders, created by a working group of the European Society for the Study of Tourette Syndrome (ESSTS). A systematic literature search was conducted to obtain original studies of psychological interventions for tic disorders, published since the initial European clinical guidelines were issued. Relevant studies were identified using computerized searches of the MEDLINE and PsycINFO databases for the years 2011-2019 and a manual search for the years 2019-2021. Based on clinical consensus, psychoeducation is recommended as an initial intervention regardless of symptom severity. According to a systematic literature search, most evidence was found for Habit Reversal Training (HRT), primarily the expanded package Comprehensive Behavioral Intervention for Tics (CBIT). Evidence was also found for Exposure and Response Prevention (ERP), but to a lesser degree of certainty than HRT/CBIT due to fewer studies. Currently, cognitive interventions and third-wave interventions are not recommended as stand-alone treatments for tic disorders. Several novel treatment delivery formats are currently being evaluated, of which videoconference delivery of HRT/CBIT has the most evidence to date. To summarize, when psychoeducation alone is insufficient, both HRT/CBIT and ERP are recommended as first-line interventions for tic disorders. As part of the development of the clinical guidelines, a survey is reported from ESSTS members and other tic disorder experts on preference, use and availability of psychological interventions for tic disorders

Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study

: ObjectiveTo investigate the association between Group-A streptococcal (GAS) infections and tic incidence among unaffected children with a family history of chronic tic disorders (CTD).MethodsIn a prospective cohort study, children with no history for tics aged 3 to 10 years with a first-degree relative with CTD were recruited from the European Multicentre Tics in Children Study (EMTICS) across 16 European centres. Presence of GAS infection was assessed using throat swabs, serum Anti-streptolysin O titres (ASOT) and Anti-DNAse B (ADB) titres blinded to clinical status. GAS exposure was defined using four different definitions based on these parameters. Cox regression analyses with time-varying GAS exposure were conducted to examine the association of onset of tics and GAS exposure during follow-up. Sensitivity analyses were conducted using Cox regression and logistic regression analyses.ResultsA total of 260 children were recruited whilst one subject was found to have tic onsets before study entry and therefore was excluded. 61 children (23.6%) developed tics over an average follow-up period of 1 (SD 0.7) year. There was a strong association of sex and onset of tics, with girls having an approximately 60% lower risk of developing tics compared to boys (HR: 0.4, 95% CI 0.2-0.7). However, there was no statistical evidence to suggest an association of any of the four GAS exposure definitions with tic onset (GAS exposure definition 1: HR=0.310, 95% CI: 0.037-2.590; definition 2: HR=0.561, 95% CI: 0.219-1.436; definition 3: HR=0.853, 95% CI: 0.466-1.561; definition 4: HR=0.725, 95% CI: 0.384-1.370).ConclusionThese results do not suggest an association of GAS exposure and development of tics.Classification of EvidenceThis study provides Class I evidence that Group-A streptococcal exposure does not associate with the development of tics in children with first-degree relatives with chronic tic disorder

Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study

BACKGROUND AND OBJECTIVES: The goal of this work was to investigate the association between group A streptococcal (GAS) infections and tic incidence among unaffected children with a family history of chronic tic disorders (CTDs). METHODS: In a prospective cohort study, children with no history for tics who were 3 to 10 years of age with a first-degree relative with a CTD were recruited from the European Multicentre Tics in Children Study (EMTICS) across 16 European centers. Presence of GAS infection was assessed with throat swabs, serum anti–streptolysin O titers, and anti-DNAse titers blinded to clinical status. GAS exposure was defined with 4 different definitions based on these parameters. Cox regression analyses with time-varying GAS exposure were conducted to examine the association of onset of tics and GAS exposure during follow-up. Sensitivity analyses were conducted with Cox regression and logistic regression analyses. RESULTS: A total of 259 children were recruited; 1 child was found to have tic onset before study entry and therefore was excluded. Sixty-one children (23.6%) developed tics over an average follow-up period of 1 (SD 0.7) year. There was a strong association of sex and onset of tics, with girls having an ≈60% lower risk of developing tics compared to boys (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.2–0.7). However, there was no statistical evidence to suggest an association of any of the 4 GAS exposure definitions with tic onset (GAS exposure definition 1: HR 0.310, 95% CI 0.037–2.590; definition 2: HR 0.561, 95% CI 0.219–1.436; definition 3: HR 0.853, 95% CI 0.466–1.561; definition 4: HR 0.725, 95% CI 0.384–1.370). DISCUSSION: These results do not suggest an association between GAS exposure and development of tics. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that group A streptococcal exposure does not associate with the development of tics in children with first-degree relatives with chronic tic disorder

Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders

Genome-wide Association Study points to novel locus for Gilles de la Tourette Syndrome

BACKGROUND: Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture, characterized by multiple motor tics and at least one vocal tic persisting for more than one year. METHODS: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6,133 TS individuals and 13,565 ancestry-matched controls. RESULTS: We identified a genome-wide significant locus on chromosome 5q15. Integration of eQTL, Hi-C and GWAS data implicated the NR2F1 gene and associated lncRNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring on brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume. CONCLUSIONS: Our work presents novel insights in the neurobiology of TS opening up new directions for future studies