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Background: Since the COVID-19 pandemic, movement disorder clinics have seen an increase in patients with an unusual type of tic-like symptoms: young adults with abrupt onset complex behaviors. It was quickly suspected that these patients suffered from functional neurological symptoms, later named Functional Tic-Like Behaviors (FTLB). Subsequent research on the differential diagnosis between FTLB and tics has been substantial and led to the development of diagnostic checklists., Objectives: We conducted a theoretical reappraisal of the FTLB literature to clarify the validity of the concept and its diagnostic implications., Methods: This paper addresses several key aspects of the current FTLB literature: circular reasoning, the complications of the FTLB phenomenology and demographics, the impact of FTLB on tic literature at large, and issues with alignment of the FTLB concept with the diagnostic criteria for functional disorders., Results: The clinical approach to FTLB might involve circular reasoning due to a lack of clinical benchmarks. The FTLB phenomenology and demographics may need more work to ensure a lack of bias and a proper description of this patient group including a clear distinction from tics. The impact of the FTLB discussion on the wider literature needs consideration. The validation of positive signs may help with both these endeavors and pave way to the inclusion of FTLB within psychiatric classification systems. Furthermore, the coexistence of FTLB and tics within the same patient needs to be addressed., Conclusion: More research may be needed to fully establish the diagnosis of FTLB and differentiate it from tics., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

In this, the tenth annual update for the F1000Research Tics collection, we summarize research reports from 2023 on Gilles de la Tourette syndrome and other tic disorders. The authors welcome article suggestions and thoughtful feedback from readers., Competing Interests: Competing interests: AH is a consultant for Noema Pharma. PA has received royalties from the Tourette OCD Alberta Network. CD is a consultant for Medtronic. NMD has no conflicts of interest. VC has no conflict of interest. KU participated in a clinical trial sponsored by Emalex Biosciences. PP has no conflict of interest. AT has no conflict of interest. CAC has no conflict of interest. NSZ participated in clinical trial supported by Emalex and Nuvelution. She received scientific grants from the Polish Neurological Society, European Stroke Organisation, Polish Ministry of Health, Polish Foundation of Science, Tourette Association of America, American Academy of Neurology and American Brain Foundation. She received speaker honoraria from Biogen. PP was supported by EMTICS (Grant No. 278367), TS-EUROTRAIN (Grant No. 316978), the National Institute of Neurological Disorders and Stroke (Grant No. R01NS105746), U.S. National Science Foundation (Grant Nos. 2006929 and 1715202), and the National Institute of Mental Health (Grant No. R01MH126213). KMV has received financial or material research support from EU (FP7-HEALTH-2011 No. 278367, FP7-PEOPLE-2012-ITN No. 316978), DFG: GZ MU 1527/3-1 and GZ MU 1527/3-2, BMBF: 01KG1421, National Institute of Mental Health (NIMH), Tourette Gesellschaft Deutschland e.V., Else-Kröner-Fresenius-Stiftung, GW pharmaceuticals, Almirall, Abide Therapeutics, Emalex Biosciences, Inc., Noema Pharma, CannaXan, and Therapix Biosiences. She has received consultant's and other honoraria from Abide Therapeutics, adjupharm, Alexion, AMP Alternative Medical Products GmbH, Ingelheim International GmbH, Bionorica Ethics GmbH, CannaMedical Pharma GmbH, Canopy Grouth, Columbia Care, CTC Communications Corp., Demecan, Enua pharma, Ethypharm GmbH, Eurox Group, Global Praxis Group Limited, Hormosan Pharma GmbH, Lundbeck, MCI Germany, Neuraxpharm, Noema Pharma, Sanity Group, Stadapharm GmbH, Synendos Therapeutics AG, Syqe, Tilray, and Zambon. She is an advisory/scientific board member for Alexion, Branchenverband Cannabiswirtschaft e.V. (BvCW), CannaMedical Pharma GmbH, Bionorica Ethics GmbH, CannaXan GmbH, Canopy Growth, Columbia Care, Ethypharm GmbH, Hormosan Pharma GmbH, IMC Germany, Leafly Deutschland GmbH, Neuraxpharm, Sanity Group, Stadapharm GmbH, Synendos Therapeutics AG, Syqe Medical Ltd., Therapix Biosciences Ltd., and Tilray. She has received speakers fees from Agaplesion Frankfurter Diakonie Kliniken gemeinnützige GmbH, Almirall, Aphria Deutschland GmbH, Arbeitsgemeinschaft Cannabis als Medizin (ACM), Bedrocan, Branchenverband Cannabiswirtschaft e.V. (BvCW), Camurus, CEREBRO SPAIN BIDCO S.L, Cogitando GmbH, Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde (DGPPN), Diplomado Internacional de Endocannabinología (Programa Universitario de Investigación en Salud - PUIS, UNAM), Dresden International University (DIU), Emalex, Eurox Deutschland GmbH, Ever pharma GmbH, Georgia Medical Cannabis Project (GMCP), GROW, Hessische Landesstelle für Suchtfragen e.V. (HLS), LIO Pharmaceuticals GmbH, Medizinischer Dienst Westfalen Lippe, Meinhardt Congress GmbH, PR Berater, Spectrum Therapeutics GmbH, Swiss Alpinopharm, targoEvent GmbH, Takeda GmbH, Tilray, von Mende Marketing GmbH, and Wayland Group. She has received royalties from Deutsches Ärzteblatt, Der Neurologie und Psychiater, Elsevier, Medizinisch Wissenschaftliche Verlagsgesellschaft Berlin, and Kohlhammer. She served as a guest editor for Frontiers in Neurology on the research topic "The neurobiology and genetics of Gilles de la Tourette syndrome: new avenues through large-scale collaborative projects", is an associate editor for "Cannabis and Cannabinoid Research", an Editorial Board Member of "Medical Cannabis and Cannabinoids" and "MDPI-Reports" and a scientific board member for "Zeitschrift für Allgemeinmedizin". SMB was supported by the Clinical Research Training Scholarship in Tourette syndrome from the Tourette Association of America and the American Brain Foundation, in collaboration with the American Academy of Neurology. PA has received funding from Region Skåne, The Crafoord Foundation, L.J. Boëthius Stiftelse, Stiftelsen Lindhaga, The Söderström Königska Foundation, Fredrik och Ingrid Thurings stiftelse, and The Sven Jerring Foundation outside the submitted work. KJB participated in a clinical trial sponsored by Emalex Biosciences and was an unpaid consultant for Noema Pharma AG; he received research support from Zhittya Genesis Medicine and from NIH (R01MH118217, UL1TR002345, R01MH126213, R21NS133875)., (Copyright: © 2024 Hartmann A et al.)

Objectives: Objectively validated pediatric sleep questionnaires covering a broader age range and different sleep disturbances are lacking, therefore we developed the Sleep Screening Questionnaire Children and Adolescents (SSQ-CA) and compared it with objective sleep parameters., Methods: This child-reported questionnaire was developed by a multidisciplinary panel and face validated. In a cross-sectional prospective design, participants aged 6-17, answered the questionnaire twice with 21-28 days in between, wore actigraphy (AG) and kept a sleep diary for seven nights and home-polysomnography (PSG) for one of these nights. Exploratory factor analyses (EFA), reliability and validity assessments were performed., Results: Of the 139 participants, 128 (F:47.7%, AG: n = 128, PSG: n = 59), were included in the analyses. Mean age: 11.3 years (SD: 2.9). EFA revealed 11 factors and 40 items loading above r = 0.4. Subscale internal consistency: 0.54-0.92. Subscale test-retest reliability: r = 0.71-0.87. Total sleep time (TST) from SSQ-CA on weekdays correlated with PSG (r = 0.48, p = 0.001) and with AG (r = 0.75, p < 0.001). The subscale total score for "Sleep duration and latency" correlated with TST from AG (r = -0.19, p = 0.03) and sleep latency (r = 0.31, p < 0.001), but not for PSG variables. The subscale "Awakenings" showed no correlation with objective measures whereas "Circadian rhythm" correlated to AG-derived mid-sleep time (r = 0.34, p < 0.001)., Conclusions: The SSQ-CA shows adequate reliability for the 6-17-year-olds and acceptable criterion validity for two subscales. It appears to be a useful tool for screening for sleep disturbances in combination with objective tools as the subjective and objective parameters seem to uncover different aspects of sleep., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cecilie Paulsrud reports financial support was provided by Danish Diabetes And Endocrine Academy. Cecilie Paulsrud reports financial support was provided by Toyota Foundation. Cecilie Paulsrud reports financial support was provided by Danish Medical Association. Cecilie Paulsrud reports financial support was provided by Holms Memorial Legatee. Steffen Ullitz Thorsen reports financial support was provided by Danish Diabetes Association. Nanette Mol Debes reports financial support was provided by The AP Møller Support Foundation. Nanette Mol Debes reports financial support was provided by Dr Louise Childrens Hospital Research Foundation. Cecilie Paulsrud reports financial support was provided by Professor Kirsten Nørgaard (Steno Diabetes Center Copenhagen). Cecilie Paulsrud reports financial support was provided by Capitol Region of Denmark Artificial Intelligence Foundation. Cecilie Paulsrud reports financial support was provided by Factuality of Health Sciences Foundation University of Copenhagen., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

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).)

Tourette syndrome (TS) is characterized by multiple motor and vocal tics, and high-comorbidity rates with other neuropsychiatric disorders. Obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), major depressive disorder (MDD), and anxiety disorders (AXDs) are among the most prevalent TS comorbidities. To date, studies on TS brain structure and function have been limited in size with efforts mostly fragmented. This leads to low-statistical power, discordant results due to differences in approaches, and hinders the ability to stratify patients according to clinical parameters and investigate comorbidity patterns. Here, we present the scientific premise, perspectives, and key goals that have motivated the establishment of the Enhancing Neuroimaging Genetics through Meta-Analysis for TS (ENIGMA-TS) working group. The ENIGMA-TS working group is an international collaborative effort bringing together a large network of investigators who aim to understand brain structure and function in TS and dissect the underlying neurobiology that leads to observed comorbidity patterns and clinical heterogeneity. Previously collected TS neuroimaging data will be analyzed jointly and integrated with TS genomic data, as well as equivalently large and already existing studies of highly comorbid OCD, ADHD, ASD, MDD, and AXD. Our work highlights the power of collaborative efforts and transdiagnostic approaches, and points to the existence of different TS subtypes. ENIGMA-TS will offer large-scale, high-powered studies that will lead to important insights toward understanding brain structure and function and genetic effects in TS and related disorders, and the identification of biomarkers that could help inform improved clinical practice., Competing Interests: Authors IN and SR were employed by the company Forschungszentrum Jülich GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Paschou, Jin, Müller-Vahl, Möller, Rizzo, Hoekstra, Roessner, Mol Debes, Worbe, Hartmann, Mir, Cath, Neuner, Eichele, Zhang, Lewandowska, Munchau, Verrel, Musil, Silk, Hanlon, Bihun, Brandt, Dietrich, Forde, Ganos, Greene, Chu, Grothe, Hershey, Janik, Koller, Martin-Rodriguez, Müller, Palmucci, Prato, Ramkiran, Saia, Szejko, Torrecuso, Tumer, Uhlmann, Veselinovic, Wolańczyk, Zouki, Jain, Topaloudi, Kaka, Yang, Drineas, Thomopoulos, White, Veltman, Schmaal, Stein, Buitelaar, Franke, van den Heuvel, Jahanshad, Thompson and Black.)

Based on its prevalence, Tourette syndrome cannot be considered a rare condition. However, in this opinion article, we make the claim that it should nonetheless be considered as an orphan or neglected disease., Competing Interests: Competing interests: Andreas Hartmann has received consultant's honoraria from Lundbeck and Noema Pharma. Natalia Szejko: None. Nanette Mol Debes: None. Andrea E. Cavanna: None. Kirsten Müller-Vahl: Financial or material research support from EU (FP7-HEALTH-2011 No. 278367, FP7-PEOPLE-2012-ITN No. 316978) DFG: GZ MU 1527/3-1 and GZ MU 1527/3-2, BMBF: 01KG1421, National Institute of Mental Health (NIMH), Tourette Gesellschaft Deutschland e.V. Else-Kröner-Fresenius-Stiftung, GW pharmaceuticals, Almirall Hermal GmbH, Abide Therapeutics, and Therapix Biosiences. She has received consultant's honoraria from Abide Therapeutics, Boehringer Ingelheim International GmbH, Bionorica Ethics GmbH, CannaMedical Pharma GmbH, Canopy Grouth, Columbia Care, CTC Communications Corp., Demecan, Eurox Deutschland GmbH, Global Praxis Group Limited, IMC Germany, Lundbeck, Sanity Group, Stadapharm GmbH, Synendos Therapeutics AG, and Tilray. She is an advisory/scientific board member for CannaMedical Pharma GmbH, Bionorica Ethics GmbH, CannaXan GmbH, Canopy Growth, Columbia Care, IMC Germany, Leafly Deutschland GmbH, Sanity Group, Syqe Medical Ltd., Therapix Biosciences Ltd., and Wayland Group. She has received speaker’s fees from Aphria Deutschland GmbH, Almirall, Cogitando GmbH, Emalex, Eurox Deutschland GmbH, Ever pharma GmbH, Meinhardt Congress GmbH, PR Berater, Spectrum Therapeutics GmbH, Takeda GmbH, Tilray, Wayland Group. She has received royalties fromDeutsches Ärzteblatt, Der Neurologie und Psychiater, Elsevier, Medizinisch Wissenschaftliche Verlagsgesellschaft Berlin, and Kohlhammer. She served as a guest editor for Frontiers in Neurology on the research topic “The neurobiology and genetics of Gilles de la Tourette syndrome: new avenues through large-scale collaborative projects”, is an associate editor for “Cannabis and Cannabinoid Research” and an Editorial Board Member of “Medical Cannabis and Cannabinoids” und “MDPI-Reports” and a Scientific board member for “Zeitschrift für Allgemeinmedizin”., (Copyright: © 2021 Hartmann A et al.)

Based on its prevalence, Tourette syndrome cannot be considered a rare disease. However, in this opinion article, we make the claim that it should nonetheless be considered as an orphan or neglected disease., Competing Interests: Competing interests: Andreas Hartmann has received consultant's honoraria from Lundbeck and Noema Pharma. Natalia Szejko: None. Nanette Mol Debes: None. Andrea E. Cavanna: None. Kirsten Müller-Vahl: Financial or material research support from EU (FP7-HEALTH-2011 No. 278367, FP7-PEOPLE-2012-ITN No. 316978) DFG: GZ MU 1527/3-1 and GZ MU 1527/3-2, BMBF: 01KG1421, National Institute of Mental Health (NIMH), Tourette Gesellschaft Deutschland e.V. Else-Kröner-Fresenius-Stiftung, GW pharmaceuticals, Almirall Hermal GmbH, Abide Therapeutics, and Therapix Biosiences. She has received consultant's honoraria from Abide Therapeutics, Boehringer Ingelheim International GmbH, Bionorica Ethics GmbH, CannaMedical Pharma GmbH, Canopy Grouth, Columbia Care, CTC Communications Corp., Demecan, Eurox Deutschland GmbH, Global Praxis Group Limited, IMC Germany, Lundbeck, Sanity Group, Stadapharm GmbH, Synendos Therapeutics AG, and Tilray. She is an advisory/scientific board member for CannaMedical Pharma GmbH, Bionorica Ethics GmbH, CannaXan GmbH, Canopy Growth, Columbia Care, IMC Germany, Leafly Deutschland GmbH, Sanity Group, Syqe Medical Ltd., Therapix Biosciences Ltd., and Wayland Group. She has received speaker’s fees from Aphria Deutschland GmbH, Almirall, Cogitando GmbH, Emalex, Eurox Deutschland GmbH, Ever pharma GmbH, Meinhardt Congress GmbH, PR Berater, Spectrum Therapeutics GmbH, Takeda GmbH, Tilray, Wayland Group. She has received royalties fromDeutsches Ärzteblatt, Der Neurologie und Psychiater, Elsevier, Medizinisch Wissenschaftliche Verlagsgesellschaft Berlin, and Kohlhammer. She served as a guest editor for Frontiers in Neurology on the research topic “The neurobiology and genetics of Gilles de la Tourette syndrome: new avenues through large-scale collaborative projects”, is an associate editor for “Cannabis and Cannabinoid Research” and an Editorial Board Member of “Medical Cannabis and Cannabinoids” und “MDPI-Reports” and a Scientific board member for “Zeitschrift für Allgemeinmedizin”., (Copyright: © 2021 Hartmann A et al.)

Objective: To examine prospectively the association between group A Streptococcus (GAS) pharyngeal exposures and exacerbations of tics in a large multicenter population of youth with chronic tic disorders (CTD) across Europe., Methods: We followed up 715 children with CTD (age 10.7 ± 2.8 years, 76.8% boys), recruited by 16 specialist clinics from 9 countries, and followed up for 16 months on average. Tic, obsessive-compulsive symptom (OCS), and attention-deficit/hyperactivity disorder (ADHD) severity was assessed during 4-monthly study visits and telephone interviews. GAS exposures were analyzed using 4 possible combinations of measures based on pharyngeal swab and serologic testing. The associations between GAS exposures and tic exacerbations or changes of tic, OC, and ADHD symptom severity were measured, respectively, using multivariate logistic regression plus multiple failure time analyses and mixed effects linear regression., Results: A total of 405 exacerbations occurred in 308 of 715 (43%) participants. The proportion of exacerbations temporally associated with GAS exposure ranged from 5.5% to 12.9%, depending on GAS exposure definition. We did not detect any significant association of any of the 4 GAS exposure definitions with tic exacerbations (odds ratios ranging between 1.006 and 1.235, all p values >0.3). GAS exposures were associated with longitudinal changes of hyperactivity-impulsivity symptom severity ranging from 17% to 21%, depending on GAS exposure definition., Conclusions: This study does not support GAS exposures as contributing factors for tic exacerbations in children with CTD. Specific workup or active management of GAS infections is unlikely to help modify the course of tics in CTD and is therefore not recommended., (© 2021 American Academy of Neurology.)

Objective: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder characterized by tics and frequent comorbidities. Although tics often improve during adolescence, recent studies suggest that comorbid obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) tend to persist. This large prospective follow-up study describes the clinical course of tics and comorbidities during adolescence and the prevalence of coexisting psychopathologies., Method: The clinical cohort was recruited at the Danish National Tourette Clinic, and data were collected at baseline (n = 314, age range 5-19 years) and at follow-up 6 years later (n = 227) to establish the persistence and severity of tics and comorbidities. During follow-up, the Development and Well-Being Assessment (DAWBA) was used to diagnose coexisting psychopathologies. Repeated measures of severity scores were modeled using mixed effects models., Results: Tic severity declined yearly (0.8 points, CI: 0.58-1.01, on the Yale Global Tic Severity Scale [YGTSS]) during adolescence; 17.7% of participants above age 16 years had no tics, whereas 59.5% had minimal or mild tics, and 22.8% had moderate or severe tics. Similarly, significant yearly declines in severity of both OCD (0.24, CI: 0.09-0.39, on the Yale-Brown Obsessive Compulsive Scale for Adults [Y-BOCS] and Yale-Brown Obsessive Compulsive Scale for Children [CY-BOCS]) and ADHD (0.42, CI: 0.32-0.52, DSM-IV) were recorded. At follow-up, 63.0% of participants had comorbidities or coexistent psychopathologies, whereas 37.0% had pure TS., Conclusion: Severity of tics, OCD, and ADHD were significantly associated with age and declined during adolescence. However, considerable comorbidities and coexisting psychopathologies persist throughout adolescence and require monitoring by clinicians., (Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Gilles de la Tourette syndrome (GTS) is a complex neuropsychiatric disorder with a strong genetic influence where copy number variations are suggested to play a role in disease pathogenesis. In a previous small-scale copy number variation study of a GTS cohort (n = 111), recurrent exon-affecting microdeletions of four genes, including the gene encoding arylacetamide deacetylase (AADAC), were observed and merited further investigations., Methods: We screened a Danish cohort of 243 GTS patients and 1571 control subjects for submicroscopic deletions and duplications of these four genes. The most promising candidate gene, AADAC, identified in this Danish discovery sample was further investigated in cohorts from Iceland, the Netherlands, Hungary, Germany, and Italy, and a final meta-analysis, including a total of 1181 GTS patients and 118,730 control subjects from these six European countries, was performed. Subsequently, expression of the candidate gene in the central nervous system was investigated using human and mouse brain tissues., Results: In the Danish cohort, we identified eight patients with overlapping deletions of AADAC. Investigation of the additional five countries showed a significant association between the AADAC deletion and GTS, and a final meta-analysis confirmed the significant association (p = 4.4 × 10(-4); odds ratio = 1.9; 95% confidence interval = 1.33-2.71). Furthermore, RNA in situ hybridization and reverse transcription-polymerase chain reaction studies revealed that AADAC is expressed in several brain regions previously implicated in GTS pathology., Conclusions: AADAC is a candidate susceptibility factor for GTS and the present findings warrant further genomic and functional studies to investigate the role of this gene in the pathogenesis of GTS., (Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Tourette syndrome (TS) is a complex neuropsychiatric disorder characterized by multiple motor and vocal tics and is often accompanied by comorbidities such as attention deficit hyperactivity disorder and obsessive-compulsive disorder. The complex etiology of TS and its co-occurrence with other disorders impedes linking genetic changes with disease segregation. One of the few genes that has been linked to TS is the SLITRK1 (Slit and Trk-like 1) gene, where four variations have been suggested as possible disease-associated changes. One of these variations, which has been reported in six unrelated TS patients, was a noncoding variant (var321) at the 3'-untranslated region of SLITRK1 within a conserved binding site for microRNA has-mir-189. To elucidate the potential role of var321 in disease pathogenesis, a cohort of 112 deeply phenotyped Danish TS patients was investigated for this variation. We could not detect var321 in the present cohort, suggesting that this is not a common variant among Danish TS patients.