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In this study, 120 undergraduate students were asked to rate the social acceptability of a male and female who portrayed different habit behaviors (motor tics, vocal tics, Tourette's disorder, and trichotillomania). The portrayals of these behaviors were clinically valid as viewed by mental health professionals. Each habit behavior was portrayed in a variety of frequency/topography combinations including low frequency/mild topography, low frequency/severe topography, high frequency/mild topography, and high frequency/ severe topography. Participants were randomly assigned to one of four habit conditions (motor tic, vocal tic, Tourette's disorder, and trichotillomania) and were asked to rate the social acceptability of the frequency/topography combinations exhibited by each actor. Results showed that across the various habit conditions, the man with the habit was seen as less socially acceptable than the woman with the habit. In addition, low-frequency habit behaviors were more acceptable than high-frequency behaviors, and behaviors with mild topographies were more acceptable than those with severe topography habits. Motor tics were seen as more acceptable than vocal tics, Tourette's disorder, or trichotillomania. Implications and directions for future research are discussed. [ABSTRACT FROM AUTHOR]

Peer relationships, social skills, self-esteem, parental psychopathology, and family functioning of children with Tourette's disorder and a chronic disease control group of children with diabetes mellitus were compared. Children with Tourette's disorder had poorer peer relationships than their classmates and were more likely to have extreme scores reflecting increased risk for peer relationship problems than children with diabetes mellitus, but did not report self-esteem problems or social skills deficits. Measures of peer relationships were not related to severity or duration of tics. Children with Tourette's disorder and Attention Deficit Hyperactivity Disorder were at increased risk for poor peer relationships. The psychosocial problems of children with Tourette's disorder do not appear to be the generic result of having a chronic disease. [ABSTRACT FROM AUTHOR]

- The purpose of this paper is to assess how 29 different environmental factors affected Tourette symptomatology in 14 children and adolescents (6.6-14.5 years; mean 10.3) who had never received any medication for their disorder. Assessment was based on patients' responses to the Tourette Syndrome (TS) Questionnaire. Eleven different factors were associated with a decrease in symptoms and included doctor visits, talking to friends, and reading for pleasure. The 10 factors reported to have no impact on Tourette symptomatology included various foods, weather, and living away from home. Seventeen factors associated with an increase in Tourette symptoms included events causing anxiety, emotional trauma, and social gatherings. [ABSTRACT FROM AUTHOR]

Motor system excitability was measured in 16 children with ADHD, 16 with chronic tic disorder or Tourette’s disorder (TD), 16 with comorbid ADHD and TD, and 16 healthy control children, in a study at the University of Gottingen, Germany.

Obsessive-compulsive disorder (OCD) is a complex, multifactorial disorder with onset in either childhood or early adulthood. Lifetime prevalence has been estimated to be around 2%-3%. DSM-5 groups OCD together with closely related disorders-body dysmorphic disorder, trichotillomania (hair-pulling disorder), hoarding disorder, and excoriation disorder (skin-picking disorder)-as obsessive-compulsive and related disorders (OCRDs). In addition, DSM-5 includes a "tic-related" specifier, recognizing that OCD and Tourette syndrome/chronic tics are frequently comorbid. In recent years, the first large-scale genome-wide studies of OCRDs have emerged. These studies confirmed results from earlier twin and family studies that have demonstrated a strong genetic component to OCRDs. Furthermore, from analyses of common genetic variation, these studies offered a first insight into how the genetic risk of developing an OCRD might be connected to the genetic risk of developing another OCRD. This article is an update of the authors' previous report; it summarizes recent findings on the genetics of OCRDs and highlights some of the recent directions in OCRD genetics that will pave the way for new insights into OCRD pathophysiology., Competing Interests: The authors report no financial relationships with commercial interests., (Copyright © 2021 by the American Psychiatric Association.)

Aims: To conduct the clinical, genetic and molecular characterization of 494 Han Chinese subjects with Tic disorders (TD)., Methods: In this study, we performed the mutational analysis of 22 mitochondrial tRNA genes in a large cohort of 494 Han Chinese subjects with TD via Sanger sequencing. These variants were then assessed for their pathogenic potential via phylogenetic, functional, and structural analyses., Results: A total of 73 tRNA gene variants (49 known and 24 novel) on 22 tRNA genes were identified. Among these, 18 tRNA variants that were absent or present in <1% of 485 Chinese control patient samples were localized to highly conserved nucleotides, or changed the modified nucleotides, and had the potential structural to alter tRNA structure and function. These variants were thus considered to be TD-associated mutations. In total, 25 subjects carried one of these 18 putative TD-associated tRNA variants with the total prevalence of 4.96%., Limitations: The phenotypic variability and incomplete penetrance of tic disorders in pedigrees carrying these tRNA mutations suggested the involvement of modifier factors, such as nuclear encoded genes associated mitochondrion, mitochondrial haplotypes, epigenetic and environmental factors., Conclusion: Our data provide the evidence that mitochondrial tRNA mutations are the important causes of tic disorders among Chinese population. These findings also advance current understanding regarding the clinical relevance of tRNA mutations, and will guide future studies aimed at elucidating the pathophysiology of maternal tic disorders., (Copyright 2020 The Author(s).)

Objectives: This study aimed to evaluate the reliability and validity of the Korean Form of the Premonitory Urge for Tics Scale (K-PUTS)., Methods: Thirty-eight patients with Tourette's disorder who visited Jeonbuk National University Hospital were assessed with the K-PUTS. Together with the PUTS, the Yale Global Tic Severity Scale (YGTSS), the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), the attention-deficit/hyperactivity disorder (ADHD) rating scale (ARS), and the Adult ADHD Self-Report Scale (ASRS) were implemented to evaluate concurrent and discriminant validity., Results: The internal consistency of items on the PUTS was high, with a Cronbach's α of 0.79. The test-retest reliability of the PUTS, which was administered at 2 weeks to 2 months intervals, showed high reliability with a Pearson correlation coefficient of 0.60. There was a significant positive correlation between the overall PUTS score and the YGTSS score, showing concurrent validity. There was no correlation between the PUTS, CY-BOCS, and ASRS scores, demonstrating the discriminant validity of the PUTS. Factor analysis for construct validity revealed three factors: "presumed functional relationship between the tic and the urge to tic," "the quality of the premonitory urge," and "just right phenomena.", Conclusion: The results of this study indicate that the K-PUTS is a reliable and valid scale for rating premonitory urge of tics., Competing Interests: Conflicts of Interest The authors have no potential conflicts of interest to disclose., (Copyright © 2020 Korean Academy of Child and Adolescent Psychiatry.)

A letter to the editor is presented which discusses the cases of patients aged 18 and 41 years old with severe Tourette's syndrome and comorbid generalized anxiety disorder who required impatient treatment.

Tourette's disorder is a stigmatising developmental neuropsychiatric disorder usually commencing in early childhood and lasting for varying periods and intensities, with persistence into adulthood for about one-third of those affected as children. The potential forensic relevance of the disorder, in the context of its common comorbidities, is relatively little appreciated among forensic psychiatrists and psychologists, legal practitioners and judicial officers in spite of the fact that a significant number of young persons and adults with Tourette's disorder are charged with criminal offences. This editorial reviews the clinical and forensic literature, about the disorder, as well as significant superior court and appellate judgments and argues for better education about the relevance of the disorder for assessments of criminal culpability, likelihood of recidivism and the consequences of custodial confinement for offenders with Tourette's disorder. It identifies areas for constructive further research., Competing Interests: None.

Objective: To examine (a) the quality of life (QOL) in children with Tourette's disorder (TD) and ADHD (TD + ADHD) compared with ADHD without tics (ADHD alone) and (b) the effects of the severity of tics, ADHD symptoms, comorbid diagnoses, and family functioning on QOL., Method: The assessments included the Kiddie-Schedule for Affective Disorders and Schizophrenia, Yale Global Tic Severity Scale, ADHD Rating Scale, Pediatric Quality of Life Inventory, and Family Assessment Device., Results: The TD + ADHD group had poorer psychosocial QOL. Agreement between child and parent ratings was higher in the TD + ADHD group, and children reported higher scores than their parents in both groups. Severity of tics and ADHD symptoms had stronger negative associations with parent-reported than child-reported QOL. Significant positive correlations were detected between QOL and family functioning in both groups., Conclusion: Children with TD + ADHD have lower QOL than their peers with ADHD alone. Family functioning seems to affect QOL in both groups.

Objective: Behaviour 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., Design: A pilot, single-blind, parallel group randomised controlled trial., Setting: A specialist outpatient clinic in Sweden., Participants: Twenty-three young people with TD/PTD, aged 8-16., Interventions: Two 10-week therapist-guided and parent-guided internet-delivered programmes (called BIP TIC HRT and BIP TIC ERP)., Outcome: The 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., Results: Patients 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., Conclusions: Internet-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., Competing Interests: Competing interests: LFC and DM-C receive royalties for contributing articles to UpToDate, Wolters Kluwer Health., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Tourette 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 Analysis: This 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 Dissemination: The 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

This chapter comprehensively reviews the published record for neurosurgical, neurostimulatory, and neuroimaging evidence of the involvement of the cingulate gyrus in Gilles de la Tourette syndrome (TS). The most noteworthy evidence comes from neuroimaging. Neuroimaging findings were rarely exclusive to the cingulate cortex and tended to implicate multiple other cortices as well. Some results are reflective of obsessive-compulsive (OC) symptoms of TS. Copious findings, however, drawn from structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), resting-state functional magnetic resonance imaging (rsfMRI), task fMRI, and positron emission tomography (PET) implicate six of the eight cingulate subregions in TS. Gauged by MRI, cortical thinning and/or below-normal volume are seen in subgenual anterior cingulate cortex (sACC), pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and posterior middle cingulate cortex (pMCC), correlating with tic severity in sACC, pACC, and aMCC. Moreover, in pMCC, dorsal posterior cingulate cortex (dPCC), and ventral posterior cingulate cortex (vPCC), cortical thickness is a candidate biomarker shared across siblings with TS. Loss of cortex may reflect excitotoxicity secondary to insufficient local GABAergic inhibition, a notion supported by the few relevant MRS and PET studies conducted to date, recommending continued development of GABAergic and glutamatergic pharmacologic agents to treat TS. Measurements of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) obtained with DTI indicate that the white matter proximal to sACC, pACC, pMCC, and dPCC may also represent a seat of pathology in TS. rsfMRI reveals abnormal functional connectivity of pACC and dPCC with the globus pallidus internus, a favored target of therapeutic deep brain stimulation (DBS) for TS. In whole-brain network (graph theory) analysis, dPCC functional connectivity is related to the severity and complexity of tics. In task fMRI, in contrast, the pMCC seems to play a preeminent role in premonitory urges and preparation for tics as well as normal urges to urinate, swallow, and yawn. Strong monkey PET and EEG evidence ties vocal tics to spike discharges, α-activity, and regional blood flow in the pACC unleashed by failure of GABAergic inhibition in the ventral striatum. Tic suppression in fMRI scans is associated with increased blood oxygenation level-dependent activity in sACC, pACC, and aMCC, but decreased activity in pMCC and dPCC. Activity in the former three subregions may represent volitional effort, physical discomfort, and emotional distress that accompanies mounting tic urges; pMCC and dPCC may be more instrumental in amplifying than suppressing urges. Needs for future neuroimaging work in TS include longitudinal studies-particularly those striving to predict which individual pediatric patients will continue to suffer from TS as adults and studies of treatment response-particularly of behavioral therapies, which are as efficacious as pharmacology. Transcranial magnetic stimulation and related therapies such as cranial electrotherapy stimulation, which showed good efficacy in a recent trial, merit continued exploration. TS research using DTI, MRS, and PET will no doubt continue to benefit in coming years from technological advances such as ultrahigh-field scanners, multichannel head coils, and novel (including GABAergic and glutamatergic) ligands., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Children with persistent (chronic) tic disorders (PTDs) experience impairment across multiple domains of functioning, but given high rates of other non-tic-related conditions, it is often difficult to differentiate the extent to which such impairment is related to tics or to other problems. The current study used the Child Tourette's Syndrome Impairment Scale - Parent Report (CTIM-P) to examine parents' attributions of their child's impairment in home, school, and social domains in a sample of 58 children with PTD. Each domain was rated on the extent to which the parents perceived that impairment was related to tics versus non-tic-related concerns. In addition, the Yale Global Tic Severity Scale (YGTSS) was used to explore the relationship between tic-related impairment and tic severity. Results showed impairment in school and social activities was not differentially attributed to tics versus non-tic-related impairment, but impairment in home activities was attributed more to non-tic-related concerns than tics themselves. Moreover, tic severity was significantly correlated with tic-related impairment in home, school, and social activities, and when the dimensions of tic severity were explored, impairment correlated most strongly with motor tic complexity. Results suggest that differentiating tic-related from non-tic-related impairment may be clinically beneficial and could lead to treatments that more effectively target problems experienced by children with PTDs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Impaired response inhibition is related to neurodevelopmental disorders, such as Tourette's disorder (TD) and obsessive-compulsive disorder (OCD). Unlike OCD, in which neural correlates of response inhibition have been extensively studied, TD literature is limited. By using a Stop-Signal task, we investigated the neural mechanisms underlying response inhibition deficits in TD compared to OCD and healthy controls (HCs)., Methods: Twenty-three TD patients, 20 OCD patients and 22 HCs were scanned (3T MRI). Region-of-interest analyses were performed between TD, OCD and HCs., Results: Performance was similar across all subject groups. During inhibition TD compared with HCs showed higher right inferior parietal cortex (IPC) activation. During error processing TD compared with HCs showed hyperactivity in the left cerebellum, right mesencephalon, and right insula. Three-group comparison showed an effect of group for error-related activation in the supplementary motor area (SMA). Post-hoc analyses showed higher error-related SMA activity in TD compared with OCD and HCs. Error-related left cerebellar activity correlated positively with tic severity., Conclusions: Hyperactivation of IPC during inhibition and a widespread hyperactivated network during error processing in TD suggest compensatory inhibition- and error-related circuit recruitment to boost task performance. The lack of overlap with activation pattern in OCD suggests such compensatory mechanism is TD-specific.

We aimed to assess the effectiveness and safety of clonidine extended release (ER) treatment in Korean youth with ADHD and/or Tourette's disorder. We retrospectively reviewed the medical records of 29 children and adolescents treated with clonidine ER. The effectiveness were retrospectively measured at baseline and after 4 and 12 weeks based on the Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scores. Safety was evaluated at each visit based on spontaneous reports from the subjects or from their parents/guardians. Significant decreases in the CGI-S scores for both ADHD (F=23.478, p<0.001, partial η2=0.540) and tic symptoms (F=15.137, p<0.001, partial η2=0.443) were noted over 12 weeks. The most common adverse event was somnolence (n=9, 31.0%) and life-threatening adverse effects were not observed. Our results provide preliminary evidence for the effectiveness and safety of clonidine ER.

This study assessed the psychometric properties of a parent-reported tic severity measure, the Parent Tic Questionnaire (PTQ), and used the scale to establish guidelines for delineating clinically significant tic treatment response. Participants were 126 children ages 9 to 17 who participated in a randomized controlled trial of Comprehensive Behavioral Intervention for Tics (CBIT). Tic severity was assessed using the Yale Global Tic Severity Scale (YGTSS), Hopkins Motor/Vocal Tic Scale (HMVTS) and PTQ; positive treatment response was defined by a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions - Improvement (CGI-I) scale. Cronbach's alpha and intraclass correlations (ICC) assessed internal consistency and test-retest reliability, with correlations evaluating validity. Receiver- and Quality-Receiver Operating Characteristic analyses assessed the efficiency of percent and raw-reduction cutoffs associated with positive treatment response. The PTQ demonstrated good internal consistency (α = 0.80 to 0.86), excellent test-retest reliability (ICC = .84 to .89), good convergent validity with the YGTSS and HM/VTS, and good discriminant validity from hyperactive, obsessive-compulsive, and externalizing (i.e., aggression and rule-breaking) symptoms. A 55% reduction and 10-point decrease in PTQ Total score were optimal for defining positive treatment response. Findings help standardize tic assessment and provide clinicians with greater clarity in determining clinically meaningful tic symptom change during treatment., (Copyright © 2017. Published by Elsevier Ltd.)

Mutations in the gene SLITRK1 (Slit and Trk-like 1) have been reported in patients with Tourette's disorder (TD). We sequenced the entire SLITRK1 gene including the coding region the 5′ and 3′ untranslated region in 92 Austrian patients with TD. No nucleotide changes within the protein-coding region were identified. One patient was found to carry a variant within the 3′ untranslated region (3383g>a), which was absent in 192 control individuals and which segregated in two additional family members with tic symptoms. In conclusion, our results provide no evidence for SLITRK1 playing a major role in TD. [ABSTRACT FROM AUTHOR]

Objective: Tourette's disorder (TD) and autism spectrum disorder (ASD) share clinical features and possibly an overlapping etiology. The aims of this study were to examine ASD symptom rates in participants with TD, and to characterize the relationships between ASD symptom patterns and TD, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD)., Method: Participants with TD (n = 535) and their family members (n =234) recruited for genetic studies reported TD, OCD, and ADHD symptoms and completed the Social Responsiveness Scale Second Edition (SRS), which was used to characterize ASD symptoms., Results: SRS scores in participants with TD were similar to those observed in other clinical samples but lower than in ASD samples (mean SRS total raw score = 51; SD = 32.4). More children with TD met cut-off criteria for ASD (22.8%) than adults with TD (8.7%). The elevated rate in children was primarily due to high scores on the SRS Repetitive and Restricted Behaviors (RRB) subscale. Total SRS scores were correlated with TD (r = 0.27), OCD (r = 0.37), and ADHD (r = 0.44) and were higher among individuals with OCD symptom-based phenotypes than for those with tics alone., Conclusion: Higher observed rates of ASD among children affected by TD may in part be due to difficulty in discriminating complex tics and OCD symptoms from ASD symptoms. Careful examination of ASD-specific symptom patterns (social communication vs. repetitive behaviors) is essential. Independent of ASD, the SRS may be a useful tool for identifying patients with TD with impairments in social communication that potentially place them at risk for bullying and other negative sequelae., (Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Phenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts., Method: Assessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated., Results: The authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not., Conclusions: The analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette-unaffected mothers, suggesting that this phenotype may reflect additional Tourette syndrome (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses.

Tourette's disorder (TS) and chronic tic disorder (CTD) are neurodevelopmental disorders characterized by involuntary vocal and motor tics. Consequently, TS/CTD have been conceptualized as disorders of cognitive and motor inhibitory control. However, most neurocognitive studies have found comparable or superior inhibitory capacity among individuals with TS/CTD relative to healthy controls. These findings have led to the hypothesis that individuals with TS/CTD develop increased inhibitory control due to the constant need to inhibit tics. However, the role of cognitive control in TS/CTD is not yet understood, particularly in adults. To examine the role of inhibitory control in TS/CTD, the present study investigated this association by assessing the relationship between inhibitory control and treatment response in a large sample of adults with TS/CTD. As part of a large randomized trial comparing behavior therapy versus supportive psychotherapy for TS/CTD, a battery of tests, including tests of inhibitory control was administered to 122 adults with TS/CTD at baseline. We assessed the association between neuropsychological test performance and change in symptom severity, as well as compared the performance of treatment responders and non-responders as defined by the Clinical Global Impression Scale. Results indicated that change in symptoms, and treatment response were not associated with neuropsychological performance on tests of inhibitory control, intellectual ability, or motor function, regardless of type of treatment. The finding that significant change in symptom severity of TS/CTD patients is not associated with impairment or change in inhibitory control regardless of treatment type suggests that inhibitory control may not be a clinically relevant facet of these disorders in adults., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Tourette's disorder (TD) is a highly heritable neurodevelopmental disorder with complex genetic architecture and unclear neuropathology. Disruptions of particular genes have been identified in subsets of TD patients. However, none of the findings have been replicated, probably due to the complex and heterogeneous genetic architecture of TD that involves both common and rare variants. To understand the etiology of TD, functional analyses are required to characterize the molecular and cellular consequences caused by mutations in candidate genes. Such molecular and cellular alterations may converge into common biological pathways underlying the heterogeneous genetic etiology of TD patients. Herein, we review specific genes implicated in TD etiology, discuss the functions of these genes in the mammalian central nervous system and the corresponding behavioral anomalies exhibited in animal models, and importantly, review functional analyses that can be performed to evaluate the role(s) that the genetic disruptions might play in TD. Specifically, the functional assays include novel cell culture systems, genome editing techniques, bioinformatics approaches, transcriptomic analyses, and genetically modified animal models applied or developed to study genes associated with TD or with other neurodevelopmental and neuropsychiatric disorders. By describing methods used to study diseases with genetic architecture similar to TD, we hope to develop a systematic framework for investigating the etiology of TD and related disorders.

Over the past six decades, behavior therapy has been a major contributor to the development of evidence-based psychotherapy treatments. However, a long-standing concern with behavior therapy among many nonbehavioral clinicians has been the potential risk for symptom substitution. Few studies have been conducted to evaluate symptom substitution in response to behavioral treatments, largely due to measurement and definitional challenges associated with treated psychiatric symptoms. Given the overt motor and vocal tics associated with Tourette's disorder, it presents an excellent opportunity to empirically evaluate the potential risk for symptom substitution associated with behavior therapy. The present study examined the possible presence of symptom substitution using four methods: (a) the onset of new tic symptoms, (b) the occurrence of adverse events, (c) change in tic medications, and (d) worsening of co-occurring psychiatric symptoms. Two hundred twenty-eight participants with Tourette's disorder or persistent motor or vocal tic disorders were randomly assigned to receive behavioral therapy or supportive therapy for tics. Both therapies consisted of eight sessions over 10 weeks. Results indicated that participants treated with behavior therapy were not more likely to have an onset of new tic symptoms, experience adverse events, increase tic medications, or have an exacerbation in co-occurring psychiatric symptoms relative to participants treated with supportive therapy. Further analysis suggested that the emergence of new tics was attributed with the normal waxing and waning nature of Tourette's disorder. Findings provide empirical support to counter the long-standing concern of symptom substitution in response to behavior therapy for individuals with Tourette's disorder., (Copyright © 2015. Published by Elsevier Ltd.)

Tourette's Disorder and other chronic tic disorders are common neurodevelopmental conditions. One characteristic of tic disorders is the premonitory urge, an aversive or unpleasant sensory phenomenon that may precede tics. Initial examination of premonitory urge in pediatric tic disorders suggests that awareness and experience of sensations preceding tics may be related to anxiety and OCD. However, it may be possible that specific anxiety-related symptoms, such as anxious physiologic arousal, are particularly relevant to the experience of premonitory urge. The current study examines relationships between tic-related premonitory urge and anxiety-related symptom clusters in treatment-seeking youths with a primary diagnoses of Tourette's or other chronic tic disorder. The sample consisted of 124 youth, ages 9 to 17, who participated in the multi-site Comprehensive Behavioral Intervention for Tics randomized controlled trial (CBIT; Piacentini et al., 2010). Specific anxiety-related subtypes, including generalized worry, separation, social, and panic/somatic symptoms, as well as severity of obsessions and compulsions, were assessed as potential correlates of premonitory urge. Findings indicated that age, global tic-related impairment, and specific panic/somatic symptoms accounted for a substantial proportion of variance in youth report of premonitory urge. These findings provide information about the characteristics of premonitory urge in pediatric tic disorders, and have implications for the treatment of pediatric tic syndromes.