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Background: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year., Methods: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants., Results: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume., Conclusions: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Video-based tic detection and scoring is useful to independently and objectively assess tic frequency and severity in patients with Tourette syndrome. In trained raters, interrater reliability is good. However, video ratings are time-consuming and cumbersome, particularly in large-scale studies. Therefore, we developed two machine learning (ML) algorithms for automatic tic detection., Objective: The aim of this study was to evaluate the performances of state-of-the-art ML approaches for automatic video-based tic detection in patients with Tourette syndrome., Methods: We used 64 videos of n = 35 patients with Tourette syndrome. The data of six subjects (15 videos with ratings) were used as a validation set for hyperparameter optimization. For the binary classification task to distinguish between tic and no-tic segments, we established two different supervised learning approaches. First, we manually extracted features based on landmarks, which served as input for a Random Forest classifier (Random Forest). Second, a fully automated deep learning approach was used, where regions of interest in video snippets were input to a convolutional neural network (deep neural network)., Results: Tic detection F1 scores (and accuracy) were 82.0% (88.4%) in the Random Forest and 79.5% (88.5%) in the deep neural network approach., Conclusions: ML algorithms for automatic tic detection based on video recordings are feasible and reliable and could thus become a valuable assessment tool, for example, for objective tic measurements in clinical trials. ML algorithms might also be useful for the differential diagnosis of tics. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

The occurrence of motor/vocal tics, that is, "extra movements" and/or "extra vocalizations," is the leading diagnostic criterion for tic disorders. We show that extra movements are common also in healthy controls, so that a surplus of movements per se is not indicative of the presence of a tic disorder. This questions the usefulness of Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria for tic disorders in clinical practice. Apparently, it is not solely a surplus of movements that defines tic disorders. Instead, movement characteristics and patterns seem to play a crucial role. ANN NEUROL 2023;93:472-478., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

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., (© 2023. The Author(s).)

Premonitory urges preceding tics are a cardinal feature of Gilles de la Tourette syndrome (GTS), a developmental disorder usually starting during middle childhood. However, the temporal relation between urges and tics has only been investigated in adults. In 25 children and adolescents with GTS (8-18 years), we assess urge-tic associations, including inter-individual differences, correlation to clinical measures, and in comparison to a previously reported sample of adult GTS patients. Group-level analyses confirmed positive associations between urges and tics. However, at the individual level, less than half of participants showed positive associations, a similar proportion did not, and in two participants, the association was reversed. Tic expression and subjective urge levels correlated with corresponding clinical scores and participants with more severe tics during the urge monitor exhibited stronger urge-tic associations. Associations between reported urge levels and instantaneous tic intensity tended to be less pronounced in children and adolescents than in adult GTS patients. The observed heterogeneity of urge-tic associations cast doubt on the notion that tics are directly caused by urges. More severe tics may facilitate anticipation of tics and thereby lead to more pronounced urge-tic associations, consistent with a hypothesis of urges as a byproduct of tics., (© 2022. The Author(s).)

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., (© 2021. The Author(s).)

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., (© 2021. The Author(s).)

In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients' self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient's needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician's preferences, experience, and local regulatory requirements., (© 2021. The Author(s).)

Background: Currently, there is a marked increase of young people with sudden onset of tic-like behaviors (TLBs) resembling movements and vocalizations presented on social media videos as "Tourette's syndrome.", Objective: To delineate clinical phenomenology of TLBs after social media exposure in comparison with clinical features of Tourette's syndrome., Methods: We compared demographic and clinical variables between 13 patients with TLBs and 13 age- and sex-related patients with Tourette's syndrome., Results: Patients with TLBs had several characteristics allowing to distinguish them from patients with Tourette's syndrome, some of which discriminated perfectly (ie, abrupt symptom onset, lack of spontaneous symptom fluctuations, symptom deterioration in the presence of others) and some nearly perfectly (ie, predominantly complex movements involving trunk/extremities). Also, symptom onset was significantly later., Conclusions: TLBs after social media consumption differ from tics in Tourette's syndrome, strongly suggesting that these phenomena are categorically different conditions. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies., (© 2021. The Author(s).)

Gilles de la Tourette syndrome (GTS) can be characterized by enhanced cognitive functions related to creating, modifying and maintaining connections between stimuli and responses (S-R links). Specifically, two areas, procedural sequence learning and, as a novel finding, also event file binding, show converging evidence of hyperfunctioning in GTS. In this review, we describe how these two enhanced functions can be considered as cognitive mechanisms behind habitual behaviour, such as tics in GTS. Moreover, the presence of both procedural sequence learning and event file binding hyperfunctioning in the same disorder can be treated as evidence for their functional connections, even beyond GTS. Importantly though, we argue that hyperfunctioning of event file binding and procedural learning are not interchangeable: they have different time scales, different sensitivities to potential impairment in action sequencing and distinguishable contributions to the cognitive profile of GTS. An integrated theoretical account of hyperbinding and hyperlearning in GTS allows to formulate predictions for the emergence, activation and long-term persistence of tics in GTS., (© 2021 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Swearing, cursing, expletives - all these terms are used to describe the utterance of taboo words. Studies show that swearing makes up around 0.5 % of the daily spoken content, however, the inter-individual variability is very high. One kind of pathologic swearing is coprolalia in Tourette syndrome (TS), which describes the involuntary outburst of taboo words. Coprolalia occurs in approximately 20-30 % of all patients with TS. This review compares swearing in healthy people and coprolalia in people with TS and is the first one to develop a multidimensional framework to account for both phenomena from a similar perspective. Different research findings are embedded in one theoretical framework consisting of reasons, targets, functions/effects and influencing factors for swearing and coprolalia. Furthermore, the very limited research investigating obscene gestures and copropraxia, compulsive obscene gestures, is summarized. New research questions and gaps are brought up for swearing, obscene gestures and coprophenomena., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.

Tetrahydroisoquinolines (TIQs) such as salsolinol (SAL), norsalsolinol (NSAL) and their methylated derivatives N-methyl-norsalsolinol (NMNSAL) and N-methyl-salsolinol (NMSAL), modulate dopaminergic neurotransmission and metabolism in the central nervous system. Dopaminergic neurotransmission is thought to play an important role in the pathophysiology of chronic tic disorders, such as Tourette syndrome (TS). Therefore, the urinary concentrations of these TIQ derivatives were measured in patients with TS and patients with comorbid attention-deficit/hyperactivity disorder (TS + ADHD) compared with controls. Seventeen patients with TS, 12 with TS and ADHD, and 19 age-matched healthy controls with no medication took part in this study. Free levels of NSAL, NMNSAL, SAL, and NMSAL in urine were measured by a two-phase chromatographic approach. Furthermore, individual TIQ concentrations in TS patients were used in receiver-operating characteristics (ROC) curve analysis to examine the diagnostic value. NSAL concentrations were elevated significantly in TS [434.67 ± 55.4 nmol/l (standard error of mean = S.E.M.), two-way ANOVA, p < 0.0001] and TS + ADHD patients [605.18 ± 170.21 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] compared with controls [107.02 ± 33.18 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] and NSAL levels in TS + ADHD patients were elevated significantly in comparison with TS patients (two-way ANOVA, p = 0.017). NSAL demonstrated an AUC of 0.93 ± 0.046 (S.E.M) the highest diagnostic value of all metabolites for the diagnosis of TS. Our results suggest a dopaminergic hyperactivity underlying the pathophysiology of TS and ADHD. In addition, NSAL concentrations in urine may be a potential diagnostic biomarker of TS.

Gilles de la Tourette Syndrome (GTS) is a developmental disorder. Empirical studies and an emerging cognitive framework on GTS suggest that GTS is a disorder of abnormally strong 'perception-action binding'. Theoretical considerations imply that the effectiveness of long-established behavioral interventions might be related to a normalization of increased binding in GTS. This has not been tested yet. We examined the effect of a standardized Comprehensive Behavior Intervention for Tics (CBIT) in N = 21 adolescent GTS patients and N = 21 healthy controls on perception-action binding in an inhibitory control paradigm. Prior to CBIT, GTS patients showed compromised performance compared to controls, specifically when inhibitory control was triggered by uni-modal visual compared to bi-modal stimuli. After CBIT intervention, GTS patient's performance was at the same level as healthy controls. This is supported by a Bayesian data analysis. CBIT specifically affected inhibitory control in a condition where reconfigurations of perception-action bindings are necessary to perform inhibitory control. A power of 95% was evident for these effects. CBIT reduces increased 'binding' between perception and action in GTS and thereby increases the ability to perform response inhibition. The results are the first to provide insights as to why CBIT is effective by relating elements of this intervention to overarching cognitive theoretical frameworks on perception-action bindings.

Background: Gilles de la Tourette Syndrome (GTS) is a multifaceted neuropsychiatric developmental disorder with onset in childhood or adolescence and frequent remissions in early adulthood. A rather new emerging concept of this syndrome suggests that it is a disorder of purposeful actions, in which sensory processes and their relation to motor responses (actions) play a particularly important role. Thus, this syndrome might be conceived as a condition of altered 'perception-action binding'. In the current study, we test this novel concept in the context of inhibitory control., Methods: We examined N = 35 adolescent GTS patients and N = 39 healthy controls in a Go/Nogo-task manipulating the complexity of sensory information triggering identical actions; i.e. to inhibit a motor response. This was combined with event-related potential recordings, EEG data decomposition and source localization., Results: GTS patients showed worse performance compared to controls and larger performance differences when inhibitory control had to be exerted using unimodal visual compared to bimodal auditory-visual stimuli. This suggests increased binding between bimodal stimuli and responses leading to increased costs of switching between responses instructed by bimodal and those instructed by unimodal stimuli. The neurophysiological data showed that this was related to mechanisms mediating between stimulus evaluation and response selection; i.e. perception-action binding processes in the right inferior parietal cortex (BA40)., Conclusions: Stimulus-action inhibition binding is stronger in GTS patients than healthy controls and affects inhibitory control corroborating the concept suggesting that GTS might be a condition of altered perception-action integration (binding); i.e. a disorder of purposeful actions., (© 2018 Association for Child and Adolescent Mental Health.)

Objective: To systematically evaluate the efficacy of treatments for tics and the risks associated with their use., Methods: This project followed the methodologies outlined in the 2011 edition of the American Academy of Neurology's guideline development process manual. We included systematic reviews and randomized controlled trials on the treatment of tics that included at least 20 participants (10 participants if a crossover trial), except for neurostimulation trials, for which no minimum sample size was required. To obtain additional information on drug safety, we included cohort studies or case series that specifically evaluated adverse drug effects in individuals with tics., Results: There was high confidence that the Comprehensive Behavioral Intervention for Tics was more likely than psychoeducation and supportive therapy to reduce tics. There was moderate confidence that haloperidol, risperidone, aripiprazole, tiapride, clonidine, onabotulinumtoxinA injections, 5-ling granule, Ningdong granule, and deep brain stimulation of the globus pallidus were probably more likely than placebo to reduce tics. There was low confidence that pimozide, ziprasidone, metoclopramide, guanfacine, topiramate, and tetrahydrocannabinol were possibly more likely than placebo to reduce tics. Evidence of harm associated with various treatments was also demonstrated, including weight gain, drug-induced movement disorders, elevated prolactin levels, sedation, and effects on heart rate, blood pressure, and ECGs., Conclusions: There is evidence to support the efficacy of various medical, behavioral, and neurostimulation interventions for the treatment of tics. Both the efficacy and harms associated with interventions must be considered in making treatment recommendations., (© 2019 American Academy of Neurology.)

Objective: To make recommendations on the assessment and management of tics in people with Tourette syndrome and chronic tic disorders., Methods: A multidisciplinary panel consisting of 9 physicians, 2 psychologists, and 2 patient representatives developed practice recommendations, integrating findings from a systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence., Results: Forty-six recommendations were made regarding the assessment and management of tics in individuals with Tourette syndrome and chronic tic disorders. These include counseling recommendations on the natural history of tic disorders, psychoeducation for teachers and peers, assessment for comorbid disorders, and periodic reassessment of the need for ongoing therapy. Treatment options should be individualized, and the choice should be the result of a collaborative decision among patient, caregiver, and clinician, during which the benefits and harms of individual treatments as well as the presence of comorbid disorders are considered. Treatment options include watchful waiting, the Comprehensive Behavioral Intervention for Tics, and medication; recommendations are provided on how to offer and monitor these therapies. Recommendations on the assessment for and use of deep brain stimulation in adults with severe, treatment-refractory tics are provided as well as suggestions for future research., (© 2019 American Academy of Neurology.)

While Behavioral Therapy (BT) should be recommended as the first step in the treatment of OCD as well as TS, medication can be added for augmentation and in certain situations (e.g. family preference, BT not available or feasible) the priority may even reverse. This narrative review is given on the complexity of drug treatment in patients comorbid with obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) and other tic problems. OCD with TS is a co-occurring combination of the two generally delimitable, but in detail, also overlapping disorders which wax and wane with time but have different courses as well as necessities and options of treatment. Distinct subtypes like "tic-related OCD" are questionable. Obsessive-compulsive symptoms (OCS) and tics are frequently associated (OCS in TS up to 90%, tics in OCD up to 37%). Sensory-motor phenomena like urges and just-right feelings reflect some behavioral overlap. The main additional psychopathologies are attention-deficit hyperactivity disorder (ADHD), mood problems and anxiety. Also, hair pulling disorder and skin picking disorder are related to OCD with TS. Hence, the assessment and drug treatment of its many psychopathological problems need high clinical experience, careful planning, and ongoing evaluation/adaptation. Drugs are able to reduce clinical symptoms but cannot cure the disorders, which should be treated in parallel in their own right; i.e. for OCD serotonin reuptake inhibitors (SSRI) and for TS (tics), certain antipsychotics can be successfully prescribed. In cases of OCD with tics, when OCS responds only partially, an augmentation with antipsychotics (recommended: risperidone and aripiprazole) may improve OCS as well as tics. Also, the benzamide sulpiride, an atypical antipsychotics, may be beneficial in treating the combination of OCS, tics and anxious-depressive problems. Probably, any additional psychopathologies of OCD might attenuate the effectiveness of SSRI on OCS; on the other hand, in cases of OCD with tics, SSRI may reduce not only OCS but also stress sensitivity and emotional problems and thus leading to better selfregulatory abilities, useful to improve tic suppression. In sum, some clinical guidance can be given, but there remain many uncertainties because of a scarce database for psychopharmacotherapy in OCD with TS., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: It has been suggested that Tourette syndrome (TS) might be associated with alterations of the attention system, but the nature of these alterations and the underlying neuroanatomical network remains elusive. We aimed at investigating the functional neuroanatomical modulators of attention allocation towards predictable versus unpredictable stimuli in boys with TS., Methods: Using functional magnetic resonance imaging, we ran a harmonic expectancy violation paradigm in 17 boys with TS and 23 matched healthy controls (HCs). We presented chord sequence in which the first four chords induced a strong expectancy for a harmonic chord at the next position. In 70% this expectancy was fulfilled (harmonic), in 30% the expectancy was violated (disharmonic)., Results: HCs responded faster to the disharmonic compared to harmonic chords, indicating a stronger attention allocation towards unpredictable stimuli, while this effect was not found in boys with TS. HCs showed stronger anterior cingulate cortex (ACC) activation during disharmonic compared to harmonic chords. Boys with TS showed stronger ACC activation during harmonic chords, which was associated with greater tic severity., Conclusions: Our findings indicate that boys with TS showed altered reactions towards predictable versus unpredictable stimuli in brain regions playing an important role in attention control. This might indicate altered allocation of attention towards those stimuli.

Gilles de la Tourette syndrome (GTS) is a childhood-onset neurodevelopmental disorder that is characterized by several motor and phonic tics. Tics usually develop before 10 years of age, exhibit a waxing and waning course and typically improve with increasing age. A prevalence of approximately 1% is estimated in children and adolescents. The condition can result in considerable social stigma and poor quality of life, especially when tics are severe (for example, with coprolalia (swearing tics) and self-injurious behaviours) or when GTS is accompanied by attention-deficit/hyperactivity disorder, obsessive-compulsive disorder or another neuropsychiatric disorder. The aetiology is complex and multifactorial. GTS is considered to be polygenic, involving multiple common risk variants combined with rare, inherited or de novo mutations. These as well as non-genetic factors (such as perinatal events and immunological factors) are likely to contribute to the heterogeneity of the clinical phenotype, the structural and functional brain anomalies and the neural circuitry involvement. Management usually includes psychoeducation and reassurance, behavioural methods, pharmacotherapy and, rarely, functional neurosurgery. Future research that integrates clinical and neurobiological data, including neuroimaging and genetics, is expected to reveal the pathogenesis of GTS at the neural circuit level, which may lead to targeted interventions.

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.)

Objectives: It has been hypothesised that altered sensorimotor gating might be a core problem in Tourette Syndrome (TS). However, the underlying neurophysiological mechanisms are elusive., Methods: We applied functional magnetic resonance imaging (fMRI) to investigate the neural correlates of altered sensorimotor gating by means of prepulse inhibition (PPI) in 22 boys with TS and 22 healthy boys using tactile PPI. The electromyography of the startle response was recorded simultaneously to the acquisition of the fMRI images., Results: As expected, PPI of the startle response was reduced in boys with TS compared to the healthy boys. We found decreased PPI-related blood oxygen level-dependent (BOLD) activity in boys with TS in the middle frontal gyrus, postcentral gyrus, superior parietal cortex, cingulate gyrus and caudate body. In boys with TS PPI of the startle response was positively correlated to PPI-related BOLD activity in the superior parietal cortex., Conclusions: Our findings indicate that deficient sensorimotor gating in boys with TS is associated with reduced recruitment of brain regions responsible for the higher-order integration of somatosensory stimuli. Due to our strict sample selection we were able to reduce confounding by neural adaptation processes, long-term medication, gender or comorbidities.

Disturbances in the corpus callosum (CC) indicating altered interhemispheric connectivity have been associated with Tourette syndrome (TS). The objective of the present study was to refine knowledge about interhemispheric connectivity in TS by analyzing four different diffusion tensor imaging (DTI) parameters in a very homogeneous group of treatment-naïve boys with pure TS in comparison to male healthy controls (HC). Fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) and mean diffusivity (MD) of five CC-segments were assessed from DTI of 26 treatment-naïve boys with pure TS and 24 HC. We observed no group differences in both FA and RD. However, we found a significant effect for AD and a trend for MD, being both reduced in boys with TS in comparison to HC. Moreover, a negative correlation between AD and the Yale Global Tic Severity Scale total score was observed. Reduced AD of the CC in treatment-naïve boys with pure TS in comparison to HC may indicate that significant alterations in white matter microstructure of the CC contribute to tic symptomatology per se and seem not to be related to confounders such as consequences of long-term medication, tic performance or tic suppression., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Neurofeedback is an increasingly recognized therapeutic option in various neuropsychiatric disorders to treat dysfunctions in cognitive control as well as disorder-specific symptoms. In this review we propose that neurofeedback may also reflect a valuable therapeutic option to treat executive control functions in Gilles-de-la-Tourette syndrome (GTS). Deficits in executive control functions when ADHD symptoms appear in GTS likely reflect pathophysiological processes in cortico-thalamic-striatal circuits and may also underlie the motor symptoms in GTS. Such executive control deficits evident in comorbid GTS/ADHD depend on neurophysiological processes well-known to be modifiable by neurofeedback. However, so far efforts to use neurofeedback to treat cognitive dysfunctions are scarce. We outline why neurofeedback should be considered a promising treatment option, what forms of neurofeedback may prove to be most effective and how neurofeedback may be implemented in existing intervention strategies to treat comorbid GTS/ADHD and associated dysfunctions in cognitive control. As cognitive control deficits in GTS mostly appear in comorbid GTS/ADHD, neurofeedback may be most useful in this frequent combination of disorders., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Tics in Gilles de la Tourette syndrome (GTS) resemble fragments of normal motor behaviour but appear in an intrusive, repetitive and context-inappropriate manner. Although tics can be voluntarily inhibited on demand, the neural correlates of this process remain unclear. 14 GTS adults without relevant comorbidities participated in this study. First, tic severity and voluntary tic inhibitory capacity were evaluated outside the scanner. Second, patients were examined with resting state functional magnetic resonance imaging (RS-fMRI) in two states, free ticcing and voluntary tic inhibition. Local synchronization of spontaneous fMRI-signal was analysed with regional homogeneity (ReHo) and differences between both states (free ticcing

Tourette syndrome is a neuropsychiatric disorder characterized by tics. Tic generation is often linked to dysfunction of inhibitory brain networks. Some previous behavioral studies found deficiencies in inhibitory motor control in Tourette syndrome, but others suggested normal or even better-than-normal performance. Furthermore, neural correlates of action inhibition in these patients are poorly understood. We performed event-related functional magnetic resonance imaging during a stop-signal reaction-time task in 14 uncomplicated adult Tourette patients and 15 healthy controls. In patients, we correlated activations in stop-signal reaction-time task with their individual motor tic frequency. Task performance was similar in both groups. Activation of dorsal premotor cortex was stronger in the StopSuccess than in the Go condition in healthy controls. This pattern was reversed in Tourette patients. A significant positive correlation was present between motor tic frequency and activations in the supplementary motor area during StopSuccess versus Go in patients. Inhibitory brain networks differ between healthy controls and Tourette patients. In the latter the supplementary motor area is probably a key relay of inhibitory processes mediating both suppression of tics and inhibition of voluntary action., (© 2014 International Parkinson and Movement Disorder Society.)

The classification of tic disorders has been revised in the new fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The previously expressed suggestion to categorize tic disorders within the "Anxiety and Obsessive Compulsive Disorders" was not implemented. The section "Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence" was revised and renamed as "Neurodevelopmental Disorders." Tic disorders are classified there as movement disorders. Most of the changes are distinct improvements from both a clinical and a scientific perspective. For example, by removing the adjective "stereotype," the definition of tics is more precise and unified. Also, the new time-oriented criteria are more practical in the clinical setting, e.g., the exclusion criterion of a tic-free interval more than 3 months given for chronic tic disorders has been deleted. The renamings from "Transient" to "Provisional Tic Disorder" as well as from "Chronic" to "Persistent Tic Disorder" are welcome changes from a clinical perspective. Overall, the revision of the criteria is an important step towards providing more clarity and feasibility. However, the revised classification of tic disorders is still based only on clinical experience and not on evidence. Future studies should show whether the revised and improved criteria truly provide the optimal classification.

Accumulating data indicate a common occurrence of tic exacerbations and periods of psychosocial stress. Patients with Tourette's syndrome (TS) also exhibit aberrant markers of hypothalamic-pituitary-adrenal (HPA) axis activation. Based on these findings, a functional relationship between stress and tic disorders has been suggested, but the underlying mechanism of how stress may affect tic pathology remains to be elucidated. We suggest that dopaminergic and noradrenergic neurotransmission as well as immunology play a crucial role in mediating this relationship. Two possibilities of causal direction might be assumed: (a) psychosocial stress might lead to an exacerbation of tics via activation of HPA axis and subsequent changes in neurotransmission or immunology and (b) TS-related abnormalities in neurotransmission or immunology result in a higher vulnerability of affected patients to respond to psychosocial stress with a strong activation of the HPA axis. It may also be the case that both assumptions hold true and interact with each other., (© The Author(s) 2014.)

Gilles de la Tourette syndrome (GTS) holds a prime position as a disorder transgressing the brittle boundaries of neurology and psychiatry with an entangling web of motor and behavioral problems. With tics as the disorder's hallmark and myriads of related signs such as echo-, pali- and coprophenomena, paralleled by a broad neuropsychiatric spectrum of comorbidities encompassing attention deficit hyperactivity disorder, obsessive-compulsive disorder and self-injurious behavior and depression, GTS pathophysiology remains enigmatic. In this review, in the light of GTS phenomenology, we will focus on current theories of tic-emergence related to aberrant activity in the basal ganglia and abnormal basal ganglia-cortex interplay through cortico-striato-thalamocortical loops from an anatomical, neurophysiological and functional-neuroimaging perspective. We will attempt a holistic view to the countless major and minor drawbacks of the GTS brain and comment on future directions of neuroscientific research to elucidate this common and complex neuropsychiatric syndrome, which merits scientific understanding and social acceptance., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.)

Objective: The study examines the role of obsessive-compulsive symptoms (OCS) as a part of the psychopathology of children with chronic tic disorders (CTD) and/or attention-deficit hyperactivity disorder (ADHD)., Method: We assessed the psychopathology of four large patient groups without further psychiatric disorders: CTD (n = 112), CTD + ADHD (n = 82), ADHD (n = 129), and controls (n = 144)) by implementing the Child Behavior Checklist (CBCL). We compared the main effects for CTD and ADHD with and without including OCS as covariates., Results: Including OCS led to substantially different main effects for CTD on seven out of eight CBCL subscales. Slightly different main effects for ADHD were determined with respect to ADHD, mainly on the subscale withdrawn., Conclusions: OCS are closely related to CTD-associated psychopathology and - to a lesser extent, but nevertheless of importance in daily clinical practice - on ADHD-related symptoms. This information can be helpful in implementing more precise diagnostics and treatment in daily routine care.

The present review gives an overview of current pharmacological treatment options of tic disorders and Tourette Syndrome (TS). After a short summary on phenomenology, clinical course and comorbid conditions we review indications for pharmacological treatment in detail. Unfortunately, standardized and large enough drug trials in TS patients fulfilling evidence based medicine standards are still scarce. Treatment decisions are often guided by individual needs and personal experience of treating clinicians. The present recommendations for pharmacological tic treatment are therefore based on both scientific evidence and expert opinion. As first-line treatment of tics risperidone (best evidence level for atypical antipsychotics) or tiapride (largest clinical experience in Europe and low rate of adverse reactions) are recommended. Aripiprazole (still limited but promising data with low risk for adverse reactions) and pimozide (best evidence of the typical antipsychotics) are agents of second choice. In TS patients with comorbid attention deficit hyperactivity disorder (ADHD) atomoxetine, stimulants or clonidine should be considered, or, if tics are severe, a combination of stimulants and risperidone. When mild to moderate tics are associated with obsessive-compulsive symptoms, depression or anxiety sulpiride monotherapy can be helpful. In more severe cases the combination of risperidone and a selective serotonin reuptake inhibitor should be given. In summary, further studies, particularly randomized, double-blind, placebo-controlled trials including larger and/or more homogenous patient groups over longer periods are urgently needed to enhance the scientific basis for drug treatment in tic disorders. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Disturbances of motor circuitry are commonly encountered in Tourette syndrome (TS). The aim of this study was to investigate simple motor performance differences between boys with TS and healthy controls., Methods: We attempted to provide insight into motor network alterations by studying a group of treatment-naïve patients suffering from 'pure' TS, i.e., without comorbid symptomatology at an early stage of disease. We used functional MRI to compare activation patterns during right (preferred) and left (nonpreferred) index finger tapping between 22 TS boys (12.6 ± 1.7 years) and 22 age-matched healthy control boys., Results: Boys with TS revealed altered motor network recruitment for right (dominant) and left (nondominant) index finger tapping. Brain activation patterns in response to index finger tapping of the nonpreferred left hand reflected the most prominent differences, including activation decrease in contralateral sensorimotor cortex while recruiting premotor and prefrontal regions along with the left inferior parietal lobule to a greater extent., Conclusions: This study demonstrates clear functional differences of simple index finger tapping in early-stage TS. We suggest that this reflects the requirement for additional brain networks to keep a normal performance level during the actual task and adaptive mechanisms due to continuous tic suppression and performance in TS., (© 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.)

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.)

Forty years of research and clinical practice have proved dopamine (DA) receptor antagonists to be effective agents in the treatment of Tourette's syndrome (TS), allowing a significant tic reduction of about 70%. Their main effect seems to be mediated by the blockade of the striatal DA-D2 receptors. Various typical and atypical agents are available and there is still discord between experts about which of them should be considered as first choice. In addition, there are suggestions to use DA receptor agonists such as pergolide or non-DA-modulating agents. The present chapter is focusing on the clinical pharmacology of DA-modulating agents in the treatment of TS. The introduction outlines their clinical relevance and touches on the hypotheses of the role of DA in the pathophysiology of TS. Subsequently, general information about the mechanisms of action and adverse effects are provided. The central part of the chapter forms a systematic review of all DA-modulating agents used in the treatment of TS, including an overview of studies on their effectiveness, and a critical discussion of their specific adverse effects. The present chapter closes with a summary of the body of evidence and a description of the resulting recommendations for the pharmacological treatment of TS., (© 2013 Elsevier Inc. All rights reserved.)

Motor and vocal tics are the core symptom of Tourette syndrome (TS). Tic generation seems to develop throughout the known motor pathways. This review focuses on functional neuroimaging in order to check this assumption. Also it elucidates the alterations and interactions of motor networks in TS depending on different contexts and circumstances like resting state, spontaneous tic movements, suppression of tics and premonitory urges, voluntary goal-oriented movements as well as electrophysiological neuronal stimulation. In general, the primary tic generating motor network uses the basic motor pathways differently, interacts with secondary sensorimotor networks and neuronal systems of cognitive behavioural control in a merely hierarchical manner, changing during neurodevelopment.

Background: Tourette syndrome is a combined motor and vocal tic disorder that begins in childhood and takes a chronic course. It arises in about 1% of all children, with highly varying severity. Transient and usually mild tics are seen in as many as 15% of all children in elementary school. The diagnosis is often delayed by several years., Methods: We selectively reviewed the pertinent literature, including the guidelines of the European Society for the Study of Tourette Syndrome for the diagnosis and treatment of tic disorders., Results: Tic disorders usually take a benign course, with spontaneous improvement in adolescence in about 90% of patients. Psychoeducation is the basis of treatment in each case and almost always brings marked emotional relief. Specific treatment is needed only for more severe tics and those that cause evident psychosocial impairment. 80-90% of patients with Tourette syndrome have comorbidities (attention deficit-hyperactivity disorder, obsessive-compulsive disorder, depression, anxiety, emotional dysregulation, autoaggression), which often impair their quality of life more than the tics do and therefore become the main target of treatment. There is little evidence for the efficacy of treatment for tics. Small-scale controlled studies with a brief follow-up period have been carried out for some neuroleptic drugs. Behavior therapy should be tried before drug treatment. A further option for very severely affected adults is deep brain stimulation., Conclusion: Because of the low level of the available evidence, no definitive recommendations can be made for the treatment of tics.

Background: Despite the common notion that premonitory urges facilitate tic inhibition, no studies have investigated this question systematically. We examined the relation of the trait of premonitory urges with tics and tic suppression. We hypothesised that patients with more urges would be more efficient at inhibiting tics., Methods: 15 adult (14 men, mean age 32.2±7.9 years) pure Gilles de la Tourette syndrome patients participated. Tic severity was evaluated using the modified Rush Video Scale and by employing the Yale Global Tic Severity Scale. Tic suppressibility was assessed from videos of additional periods where patients were instructed to maximally suppress their tics. Rush score based inhibition potency was synthesised by combining the scores in the two conditions. A measure of pure motor tic inhibition potency was also generated based on the number of motor tics alone. Premonitory urges were assessed by the Premonitory Urge for Tics Scale., Results: All participants reported urges preceding their tics and were able to voluntarily suppress their tics. However, there was no correlation between urge scores and the Rush score based inhibition potency or the pure motor tic inhibition potency. Scores of the Premonitory Urge for Tics Scale correlated with the interference subscale item of the Yale Global Tic Severity Scale., Conclusions: Urges and tic inhibition are not directly related. There seem to exist at least two distinct neurophysiological systems of urge/tic generation and tic control in adult Gilles de la Tourette syndrome patients.

Tremendous progress has taken place in the last 8 years since the publication of our review on «Therapy of Tic Disorders» in the Zeitschrift für Kinder- und Jugendpsychiatrie. Several steps in treatment have been specified. For example, consensus-based indications for treatment have been published, and a detailed manual for a so-called habit-reversal training program has been developed and evaluated. In addition, new treatment options such as aripiprazole and deep-brain stimulation have been implemented. Increasing attention is being given to the disabling consequences of the commonly co-occurring psychiatric conditions known as ADHD or OCD. Nevertheless, there is still much to be learned about the treatment of tic disorders; standardized and sufficiently large drug trials in patients with tic disorders fulfilling evidence-based medicine standards are still scarce. The same is true for direct comparisons of different agents as well as of medication versus behavioral treatment. Finally, the question of how to predict the individual course of tics and how best to deal with the problems of waxing and waning of tics in this context still limits evidence base for treatment decisions. Large clinical experience is still a pre-requisite for making optimal decisions for the treatment of individual patients suffering from a tic disorder.

Aim: This study addressed whether Tourette syndrome is associated with an impairment of fine motor skills or altered interhemispheric transfer. We additionally investigated the association between interhemispheric transfer and size of the corpus callosum., Method: The sample, a subsample of our larger neuroimaging sample, included 27 treatment-naive males with 'pure' Tourette syndrome (age range 10y 2mo-14y 4mo; mean age 11y 10mo, SD 1y 2mo) and 26 matched healthy comparison children (age range 10y 2mo-14y 4mo; mean age 11y 10mo, SD 1y 1mo). A finger tapping task and the Purdue Pegboard were used to assess fine motor skills. Interhemispheric transfer time (ITT) was measured with the Poffenberger paradigm. The neuroanatomical data were derived from our previous neuroimaging study., Results: ITT was negatively correlated with the size of callosal subregion 3 (r=-0.366, p=0.028), indicating that a shorter ITT was associated with a larger corpus callosum., Interpretation: Our findings support the assumption that previously reported impairment of motor skills in Tourette syndrome does not directly result from tics but from other factors such as medication or comorbidities. Following the assumption that callosal subregion 3 in Tourette syndrome grows as a consequence of tic performance over years, our preliminary results suggest that this growth might accelerate interhemispheric transfer in Tourette syndrome., (© The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.)

In Tourette syndrome (TS), not only the tics but also the findings on deficits in motor performance indicate motor system alterations. But our knowledge about the pathophysiology of the motor system in TS is still limited. To better understand the neuronal correlates of motor performance in TS, 19 treatment-naïve boys [age 12.5 (SD 1.4) years] with TS without comorbid symptomatology were compared to an age-matched healthy control group [n = 16; age 12.9 (SD 1.6) years] in regard to brain activation during right-hand index finger tapping by means of functional magnetic resonance imaging. Group differences were found mainly in the left (contralateral) precentral gyrus, which was less activated in boys suffering from TS and in caudate nucleus as well as in medial prefrontal cortex, which was more activated compared to healthy boys. These results show that even in the first years after the onset of the disorder, an altered brain network of motor performance is recruited. These alterations in brain regions frequently associated with TS are probably based on functional changes, which are discussed in terms of early compensatory mechanisms of the motor execution network., (Copyright © 2011 Wiley Periodicals, Inc.)

Objective: Attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) are the 2 most frequent psychiatric disorders co-occurring with Tourette syndrome (TS). Both usually cause greater impairment in psychosocial functioning than the tics themselves. In a previous study, we examined the relationship of attention-deficit/hyperactivity disorder to other comorbid conditions in TS. The relationship of OCD to other comorbidities in TS still remains unclear and is the focus of the present study., Methods: Pearson's χ tests and logistic regressions (year-wise) were used to examine a cross-sectional sample of children and adolescents (n = 5060) diagnosed with TS, taken from the Tourette Syndrome International Database Consortium. We explored the relationship of OCD to other comorbid conditions in TS across different age groups., Results: In children (ages 5-10 y) with TS, higher rates of comorbidities were found in the presence compared with the absence of OCD. Adolescents (ages 11-17 y) with TS + OCD showed higher rates of internalizing (i.e., anxiety and mood) disorders when compared with those with TS - OCD. A year-wise increase of coexisting mood disorders was found for subjects with TS with and without OCD., Conclusions: Overall, children and adolescents with TS + OCD showed higher rates of comorbid disorders compared with those with TS - OCD. This underlines the necessity for a comprehensive assessment of additional comorbidities even if the 2 disorders (TS + OCD) have already been diagnosed.

Gilles de la Tourette syndrome (GTS) is characterized by multiple fluctuating motor and vocal tics. These tics are often preceded by premonitory phenomena including the urge to move, or by exaggerated bodily sensations that can lead to considerable disability and difficulties with attention and concentration. In the past the premonitory phenomena were interpreted as the driving force behind tics. However, there is not always a clear sequence of premonitory sensations followed by a tic. Also, the former typically develop around the age of 10 years, i.e. after the onset of the latter. Thus, the relationship between premonitory phenomena and tics is unclear. The present article reviews the current knowledge on this issue. Neurophysiological studies have shown some abnormalities of sensorimotor integration in GTS. In addition, structural imaging (MRT) has demonstrated a thinning of the sensorimotor cortex in children and adolescents with GTS. In contrast, an increase in fractional anisotropy as a marker of the directionality of white matter fibers underneath the pre- and postcentral gyrus has been demonstrated in adult GTS patients. These data underscore the role of developmental abnormalities and reorganisation in the somatosensory system in GTS warranting further studies. Multimodal studies including structural and functional imaging and electrophysiology in clinically well characterized GTS subgroups might foster a better understanding of somatosensory phenomena and the role of sensorimotor circuits in GTS.

To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce.