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Comprehensive Behavioral Intervention for Tics (CBIT) is recommended as a first-line treatment for Tourette syndrome in children and adults. While there is strong evidence proving its efficacy, the mechanisms of reduction in tic severity during CBIT are still poorly understood. In a recent study, our group identified a functional brain network involved in tic suppression in children with TS. We reasoned that voluntary tic suppression and CBIT may share some mechanisms and thus we wanted to assess whether functional connectivity during tic suppression was associated with CBIT outcome. Thirty-two children with TS, aged 8 to 13 years old, participated in a randomized controlled trial of CBIT a treatment-as-usual control condition. EEG was recorded during tic suppression in all participants at baseline and endpoint. We used a source-reconstructed EEG connectivity pipeline to assess functional connectivity during tic suppression. Functional connectivity during tic suppression did not change from baseline to endpoint. However, baseline tic suppression-related functional connectivity specifically predicted the decrease in vocal tic severity from baseline to endpoint in the CBIT group. Supplementary analyses revealed that the functional connectivity between the right superior frontal gyrus and the right angular gyrus was mainly driving this effect. This study revealed that functional connectivity during tic suppression at baseline predicted reduction in vocal tic severity. These results suggest probable overlap between the mechanisms of voluntary tic suppression and those of behavior therapy for tics.

Tourette disorder (TD), hallmarks of which are motor and vocal tics, has been related to functional abnormalities in large-scale brain networks. Using a fully data driven approach in a prospective, case-control study, we tested the hypothesis that functional connectivity of these networks carries a neural signature of TD. Our aim was to investigate (i) the brain networks that distinguish adult patients with TD from controls, and (ii) the effects of antipsychotic medication on these networks. Using a multivariate analysis based on support vector machine (SVM), we developed a predictive model of resting state functional connectivity in 48 patients and 51 controls, and identified brain networks that were most affected by disease and pharmacological treatments. We also performed standard univariate analyses to identify differences in specific connections across groups. SVM was able to identify TD with 67% accuracy ( = 0.004), based on the connectivity in widespread networks involving the striatum, fronto-parietal cortical areas and the cerebellum. Medicated and unmedicated patients were discriminated with 69% accuracy ( = 0.019), based on the connectivity among striatum, insular and cerebellar networks. Univariate approaches revealed differences in functional connectivity within the striatum in patients controls, and between the caudate and insular cortex in medicated unmedicated TD. SVM was able to identify a neuronal network that distinguishes patients with TD from control, as well as medicated and unmedicated patients with TD, holding a promise to identify imaging-based biomarkers of TD for clinical use and evaluation of the effects of treatment.

SUMMARY POINTS Tourette's syndrome is a tic disorder that is often associated with behavioural symptoms Diagnostic criteria are based on the presence of both motor and vocal tics; because of its varied presentations, the syndrome has the potential to be misdiagnosed Prevalence is higher than commonly assumed; coprolalia is relatively rare (10-30%) and not required for diagnosis The syndrome can cause serious distress and compromise health related quality of life The main management strategies include psychoeducation, behavioural techniques, and drugs Service provision is patchy even in developed countries and patients of all ages often \"fall through the net\" between neurology and psychiatry

IntroductionTourette syndrome and chronic tic disorder are common, disabling childhood-onset conditions. Guidelines recommend that behavioural therapy should be offered as first-line treatment for children with tics. However, there are very few trained behaviour therapists for tics and many patients cannot access appropriate care. This trial investigates whether an internet-delivered intervention for tics can reduce severity of symptoms.Methods and analysisThis parallel-group, single-blind, randomised controlled superiority trial with an internal pilot will recruit children and young people (aged 9–17 years) with tic disorders. Participants will be randomised to receive 10 weeks of either online, remotely delivered, therapist-supported exposure response prevention behavioural therapy for tics, or online, remotely delivered, therapist-supported education about tics and co-occurring conditions. Participants will be followed up mid-treatment, and 3, 6, 12 and 18 months post randomisation.The primary outcome is reduction in tic severity as measured on the Yale Global Tic Severity Scale total tic severity score. Secondary outcomes include a cost-effectiveness analysis and estimate of the longer-term impact on patient outcomes and healthcare services. An integrated process evaluation will analyse quantitative and qualitative data in order to fully explore the implementation of the intervention and identify barriers and facilitators to implementation. The trial is funded by the National Institute of Health Research (NIHR), Health Technology Assessment (16/19/02).Ethics and disseminationThe findings from the study will inform clinicians, healthcare providers and policy makers about the clinical and cost-effectiveness of an internet delivered treatment for children and young people with tics. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval from North West Greater Manchester Research Ethics Committee (ref.: 18/NW/0079).Trial registration numbers ISRCTN70758207 and NCT03483493; Pre-results.

Background Allergic rhinitis is the most common allergic disease. It can accompany psychological disorders such as tic disorders due to the prolonged course of the symptoms of allergic rhinitis. This pioneer case-control study aims to investigate tic disorders in children and adolescents under 18 years of age diagnosed with allergic rhinitis. Method The case group in this study consisted of patients who had both allergic rhinitis and tic disorders. Patients with allergic rhinitis without tic disorders were also enrolled as the control group with matched gender and age. Demographic characteristics, tic classifications, and contributing factors for allergic rhinitis and tic disorders were studied among the cases. Tic disorders were evaluated using DSM-5 criteria for the classification of tic disorders. Results 47 patients in the case group and 47 patients in the control group were included in this study. 53.2% and 46.8% were males and females in the case group, respectively. The mean age of the patients was 10.46 ± 3.97 years old. Sound tics were more common among the patients compared to motor tics. Patients with concomitant AR and tic disorders had more days per week with AR symptoms (P-value ≤ 0.001; OR (every day vs. three days a week = 11.02(2.98, 40.76))). Most patients with sound tick were women (p: 0.026), and most patients with motion tic were in the Provisional tic disorder group (p: 0.001). The history of infantile eczema was seen more in patients without sound tic (p: 0.025), and otitis media was significantly less common among patients with sound tics (p: 0.026). Provisional tic disorder was the most common class among the patients. In the case group (coexistence between allergic rhinitis and tic) compared to the control group, patients had significantly more days with AR symptoms per week. Conclusion This preliminary study indicates that Provisional tic disorder was the most common classification of tic among patients with allergic rhinitis, especially in patients with motor tics. Asthma in motor tics, a history of food allergy in infancy, and a history of infantile eczema were also common among patients with vocal tics. Also, patients with allergic rhinitis and tic had more severe disease (more symptoms per week) than those with rhinitis alone. These findings emphasize the association of tic disorders with immunological pathways.

Cannabinoid receptor 1 (CB1) signalling is critical for weight gain and for milk intake in newborn pups. This is important as in humans, low birth weight increases the risk for attention-deficit hyperactivity disorder (ADHD). Moreover, some children with ADHD also have Tourette syndrome (TS). However, it remains unclear if insufficient CB1 receptor signalling may promote ADHD/TS-like behaviours. Here, ADHD/TS-like behaviours were studied from postnatal to adulthood by exposing postnatal wild-type CB1 and Cannabinoid receptor 2 (CB2) knockout mouse pups to SR141716A (rimonabant), a CB1 receptor antagonist/inverse agonist. Postnatal disruption of the cannabinoid system by SR141716A induced vocal-like tics and learning deficits in male mice, accompanied by excessive vocalisation, hyperactivity, motor-like tics and/or high-risk behaviour in adults. In CB1 knockouts, rearing and risky behaviours increased in females. In CB2 knockouts, vocal-like tics did not develop, and males were hyperactive with learning deficits. Importantly, females were hyperactive but showed no vocal-like tics. The appearance of vocal-like tics depends on disrupted CB1 receptor signalling and on functional CB2 receptors after birth. Inhibition of CB1 receptor signalling together with CB2 receptor stimulation underlie ADHD/TS-like behaviours in males. This study suggests that the ADHD/TS phenotype may be a single clinical entity resulting from incorrect cannabinoid signalling after birth.

Chronic tic disorders (CTD) are characterized by motor and/or vocal tics. Existing data on the impact of tics in adulthood is limited by small, treatment-seeking samples or by data aggregated across adults and children. The current study explored the functional impact of tics in adults using a nationwide sample of 672 participants with a self-reported CTD. The impact of tics on physical, social, occupational/academic, and psychological functioning was assessed. Results suggested mild to moderate functional impairment and positive correlations between impairment and tic severity. Notable portions of the sample reported social or public avoidance and experiences of discrimination resulting from tics. Compared to previously reported population norms, participants had more psychological difficulties, greater disability, and lower quality of life. The current study suggests that CTDs can adversely impact functioning in adults and highlights the need for clinical interventions and systemic efforts to address tic-related impairments.

ObjectiveBehaviour therapy (BT) for Tourette’s disorder (TD) and persistent (chronic) motor or vocal tic disorder (PTD) is rarely available. We evaluated the feasibility of adapting two existing BT protocols for TD/PTD (habit reversal training (HRT) and exposure and response prevention (ERP)) into a therapist-guided and parent-guided online self-help format.DesignA pilot, single-blind, parallel group randomised controlled trial.SettingA specialist outpatient clinic in Sweden.ParticipantsTwenty-three young people with TD/PTD, aged 8–16.InterventionsTwo 10-week therapist-guided and parent-guided internet-delivered programmes (called BIP TIC HRT and BIP TIC ERP).OutcomeThe primary outcome measure was the Yale Global Tic Severity Scale. Blinded evaluators rated symptoms at baseline, post-treatment and 3-month follow-up (primary endpoint). All participants were naturalistically followed up to 12 months after treatment.ResultsPatients and parents rated the interventions as highly acceptable, credible and satisfactory. While both interventions resulted in reduced tic-related impairment, parent-rated tic severity and improved quality of life, only BIP TIC ERP resulted in a significant improvement on the primary outcome measure. Within-group effect sizes and responder rates were, respectively: d=1.12 and 75% for BIP TIC ERP, and d=0.50 and 55% for BIP TIC HRT. The therapeutic gains were maintained up to 12 months after the end of the treatment. Adverse events were rare in both groups. The average therapist support time was around 25 min per participant per week.ConclusionsInternet-delivered BT has the potential to greatly increase access to evidence-based treatment for young people with TD/PTD. Further evaluation of the efficacy and cost-effectiveness of this treatment modality is warranted.Trial registration number NCT02864589; Pre-results.

Tourette syndrome (TS) is the most common cause of tics. Tics are classified as motor and phonic tics. The latter (previously also referred to as “vocal tics”) are manifested by simple sounds (simple phonic tics) or complex, often semantically meaningful utterances (complex phonic tics). Methods: We compared the clinical and demographic features of consecutive patients with TS who exhibited simple and complex phonic tics. Results: There were 149 patients, 117 (78.5%) of whom were males; the mean age at evaluation was 19.61 ± 12.97 years. In total, 35 (23.5%) of these manifested complex phonic tics, and 26 (17.4%) had verbalizations. No statistically significant differences were observed between TS patients with simple versus complex phonic tics with respect to sex, age at onset, age at presentation, or comorbid attention-deficit/hyperactivity disorder or obsessive–compulsive disorder. Patients with complex phonic tics more frequently had trunk tics (p = 0.002), complex motor tics (p < 0.001), copropraxia (p = 0.002), a wider variety of phonic tics (p < 0.001) and greater tic severity (p = 0.001). The multivariate regression analysis showed an independent association between trunk tics and complex phonic tics. Conclusions: Complex phonic tics seem to be part of a more widely distributed, severe, and complex presentation of TS, likely representing a continuum within the spectrum of motor and phonic tics.

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by recurrent motor and vocal tics, often accompanied by obsessive–compulsive disorder and/or attention-deficit/hyperactivity disorder. While the evidence for a genetic contribution is strong, its exact nature has yet to be clarified fully. There is now mounting evidence that the genetic risks for TS include both common and rare variants and may involve complex multigenic inheritance or, in rare cases, a single major gene. Based on recent progress in many other common disorders with apparently similar genetic architectures, it is clear that large patient cohorts and open-access repositories will be essential to further advance the field. To that end, the large multicenter Tourette International Collaborative Genetics (TIC Genetics) study was established. The goal of the TIC Genetics study is to undertake a comprehensive gene discovery effort, focusing both on familial genetic variants with large effects within multiply affected pedigrees and on de novo mutations ascertained through the analysis of apparently simplex parent–child trios with non-familial tics. The clinical data and biomaterials (DNA, transformed cell lines, RNA) are part of a sharing repository located within the National Institute for Mental Health Center for Collaborative Genomics Research on Mental Disorders, USA, and will be made available to the broad scientific community. This resource will ultimately facilitate better understanding of the pathophysiology of TS and related disorders and the development of novel therapies. Here, we describe the objectives and methods of the TIC Genetics study as a reference for future studies from our group and to facilitate collaboration between genetics consortia in the field of TS.