Tourette syndrome (TS) is a neuropsychiatric and a neurodevelopmental disorder often presenting alongside other neurodevelopmental conditions such as attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), learning difficulties, and dyspraxia. TS shares genetic and neurobiologic features with ASD and ADHD, suggesting common underlying mechanisms. Recent diagnostic frameworks such as the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, APA, 2013) allow for multiple co-occurring diagnoses, reflecting the complex overlap among neurodevelopmental disorders. Whilst there are several studies stating high rates of TS in ASD and vice versa, the data about the nature of tics in those with ASD is sparse; nevertheless, it shows that they are probably not different in nature to tics present in TS. Tics in individuals with ASD can be diagnostically challenging due to overlapping motor behaviors like stereotypies. Intellectual disability (ID) further complicates tic identification, given communication difficulties and co-occurring behaviors. A pragmatic, needs-focused clinical approach is recommended, emphasizing prioritisation of presenting problems over an accumulation of diagnostic labels. This strategy facilitates targeted interventions where needed. In children with ID, differentiating between tics and stereotypies is important to avoid inappropriate management.

Abstract Tourette Syndrome and other tic disorders (TD) are common, highly heritable neurodevelopmental conditions with complex genetic architectures. We conducted a genome-wide association study of 13,247 TD cases and 536,217 European ancestry controls and identified six independent genome-wide significant loci, including a pleiotropic signal at 3p21 shared with attention-deficit/hyperactivity disorder, among other traits. Gene prioritization highlighted 20 genes, including PCDH9, HCN1, NCKIPSD, WDR6, DALRD3 , and CELSR3 . Integrative analyses provide genetic support for the role of cortico-striato-thalamo-cortical circuits in TD pathophysiology and further localize TD genetic risk to specific cell types, including dopamine D1- and D2-receptor-positive medium spiny neurons, cortical pyramidal neurons, and oligodendrocyte-lineage cells. We further demonstrate extensive genetic correlations with neurodevelopmental and psychiatric traits, but not with neurological disorders. These findings advance our understanding of the genetic basis of TD, pinpointing specific genes and cell types that drive pathophysiology and providing a foundation for future mechanistic studies.

Background: Cognitive behavioural therapies, including Exposure and Response Prevention (ERP) and Habit Reversal Therapy (HRT) are the recommended interventions for tic management. There has been emerging evidence and anecdotal client feedback that externalised attention approaches are also effective in the management of tics. As such, a novel, virtually delivered group incorporating ERP, HRT, externalised attention and mindfulness/relaxation approaches was developed. The purpose of this study was to explore the effectiveness of this tic tool kit group in the managing of tics in young people. Methods: Children and young people (CYP) with tic disorders, aged 9-17, under the care of a specialist tic and movement clinic, attended a 6-session virtual tic therapy group with one of their parents, each lasting one hour. The Yale Global Tic Severity Scale (YGTSS) was completed for 31 patients prior to and following the group, and qualitative feedback was also gathered regarding satisfaction and acceptability of the management techniques. Results: Patients' post-group YGTSS scores showed a statistically significant decrease in overall severity and impairment scores compared to pre-group scores, mostly driven by lowering in motor and phonic tic severity, rather than substantial lower functional impairment. Qualitative data illustrated that all patients reported better management of tics after having attended the virtual group. Moreover, 91.6% of attendees returned positive feedback for the virtual aspect, finding the group "more accessible" and valuing the availability of 1:1 practice with clinicians. Conclusions: These findings suggest that the cost-effective virtual group may be an effective intervention for CYP with tics disorder and provides a preliminary basis for delivering combined ERP and HRT alongside externalised attention and mindfulness/relaxation strategies. Future exploration of this novel treatment, especially with a control groups and longer follow up should be conducted to establish the degree of its effectiveness for clinical populations.

AIM:This study aimed to analyse the pathways to obtaining a diagnosis of functional tic-like behaviour (FTLBs) in the United Kingdom. METHODS:The primary caregivers of children with FTLB (n = 55) were recruited through charities and completed an anonymised survey. The authors established the pathway to any diagnosis, gaining information about their child's tics, their impact and the sequence of health-care professionals (HCPs) they had contacted that had either led or not led to a diagnosis and any support on offer. Mixed-method analyses were conducted on the surveys. RESULTS:Many of the characteristics of the children met the criteria for FTLBs, with over half of the children (n = 30; 55%) also showing self-harming and suicidal ideation behaviour. Mothers reported often finding themselves seeing more than three different services and being given differing labels for their child's symptoms (e.g., transient tics and PANDAS). There was little clear guidance on how to manage symptoms, with those who were able to access treatment offered CBT, counselling and/or medication. There were several families still waiting to be seen (n = 13; 24%); however, of those who had received a diagnosis, almost one-third had accessed support from private healthcare providers (n = 14; 25%). CONCLUSIONS:Pathways to diagnosis for young people showing FTLBs are complex, time-consuming and can involve multiple health-care contacts, with patients alternating between primary and specialised care. Our findings reflect failures in the diagnostic protocols and referral systems of health care in the United Kingdom and a general lack of understanding, specialist skill or knowledge relating to FTLBs.

Infection has been known to trigger the emergence of autoimmune movement disorders. Antibodies against Dopamine 2 receptors (D2R) have been implicated in the pathogenesis of Sydenham’s chorea (SC) and basal ganglia encephalitis (BGE). Although these antibodies have also been described in pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection (PANDAS) / Paediatric Acute Neuropsychiatric syndrome (PANS) and Tourette syndrome (TS), their role has been debated. Significant knowledge gaps remain, and numerous claims regarding the involvement of D2R and other antibodies in immune-mediated movement and neuropsychiatric disorders warrant further scrutiny. The presence of D2R antibodies remain controversial within the scientific community, largely due to variability in laboratory methodologies. Prior results across these syndromes were obtained using in vitro assays that compromised the native structure of neuronal surface antigens, raising concerns about the physiological relevance and specificity of the detected antibody interactions. Methodologies employed in cell-based assays (CBAs) for the detection of D2R antibodies, particularly concerning the efficiency and consistency of D2R DNA transfection, as well as the varying cell lines may explain heterogenous findings. The differences in anti‐D2R positivity may also be due to clinical fluctuations in SC, PANDAS/PANS and TS/TD. Research directed towards understanding the target of antibodies against D2R in different disorders, the degree of avidity and the functional alteration of the receptor signals induced by the antibodies in each disorder as well as deeper phenotyping of a subgroup in TS and PANDAS who are likely to have the antibodies, may provide greater insights.

PurposeFunctional tics (FTs) are sudden, involuntary movements or vocalisations resembling those in Tourette Syndrome but thought to arise from functional neurological mechanisms. Since the COVID-19 pandemic, there has been a sharp rise in FT presentations around the world, particularly among young people (YPs), with research linking social media platforms like TikTok to this sudden increase. Despite this surge, the lived experiences of YPs with FTs remain underexplored. This study aimed to understand how YPs experience FTs and how these affect daily life, wellbeing, sense of self, help-seeking, and coping.Materials and methodsTwelve UK-based YPs aged 13-24 were recruited through third-sector organisations and online platforms using purposive sampling. Semi-structured interviews explored onset, impact, and coping with FTs. Data were analysed using Reflexive Thematic Analysis (RTA).ResultsFour themes were identified: Life Upended (sudden disruption and emotional upheaval); Help that Hurts (invalidating or fragmented support driving reliance on online spaces); Under the Spotlight (impact of visibility on identity and wellbeing); and Coming to Terms (developing coping strategies and resilience over time).ConclusionThis study demonstrates how FTs reshape YP's lives, identities, and experiences of seeking support, highlighting the need for compassionate, contextually informed approaches across clinical and everyday environments.

BACKGROUND:During the last 5 years, functional tic-like behaviors (FTLBs) have been the center of an increasing amount of scientific research. PURPOSE:The purpose of this review was to collect this research and create an overview of what is currently known about the patient group. METHODS:PubMed, EMBASE, and Web of Science were systematically searched for relevant papers, which were then sorted based on set inclusion and exclusion criteria. This process resulted in twenty-four papers selected for extraction, the results of which were summarized. RESULTS:The results were split into three topics: characteristics, follow-ups, and treatment. Across studies on characteristics, patients with FTLB have overall higher symptom severity and complexity and a higher prevalence of anxiety and depression compared to the patients with Tourette syndrome included in the studies. The patients with Tourette syndrome had a higher prevalence of simple tics and comorbid attention-deficit/hyperactivity disorder and obsessive-compulsive disorder. However, in both populations there was considerable heterogeneity in both comorbidity profile as well as the characteristics of vocalizations and movements. The follow-up literature was relatively small but showed a general reduction in FTLB patients' symptoms over time, although spontaneous remission was rare. The treatment literature, which consisted of just two articles, showed good benefit of cognitive therapies. CONCLUSIONS:Overall, the FTLB patient group presents with a wide variety of symptoms, which tends to persist but responds well to cognitive treatment. More research is needed particularly within the treatment literature.

Objective To investigate the prognosis and co-occurring disorders, including functional neurological symptoms, in adolescents diagnosed with functional tic-like behaviour (FTLB). Design This was a single-centre tertiary study in the UK. A structured clinical interview was administered to 43 parents or carers of adolescents assessed with FTLB at their previous outpatient clinic appointment. Data collected included demographic variables, co-occurring psychiatric and neurodevelopmental diagnoses and additional functional neurological symptoms. Setting A tertiary UK paediatric tics and neurodevelopmental movement disorder service. Patients: adolescents diagnosed with FTLB during the COVID-19 pandemic. Outcome measures: the primary outcome was whether FTLB had resolved, improved, remained constant or worsened. Secondary outcomes were Children’s Global Assessment Scale scores, impact on school attendance and parent or carer work absence. Results Patient demographics support the European Society for the Study of Tourette Syndrome diagnostic criteria for FTLB, with a 100% female sex bias, adolescent onset and high levels of co-occurring disorders. Anxiety disorders were especially common (70%), as were other functional neurological symptoms. While the majority (65%) of parents reported that the young people had resolution or improvement in the severity of FTLB symptoms at follow-up, a significant minority (16%) saw no change and a fifth reported worsening symptoms. Conclusions FTLB show high co-occurrence with psychiatric and neurodevelopmental disorders, along with other functional neurological symptoms. In this study, the prognosis was poor for a fifth of patients diagnosed with FTLB.

Sensory, eating and mealtime (SEM) challenges are common among young people with neurodevelopmental movement disorders but are rarely assessed during initial clinical consultations. This quality improvement project aimed to evaluate the impact of routine SEM screening on identifying these challenges and improving documentation and follow-up in a specialist paediatric movement disorder clinic in England. Using the SHIFT-Evidence Framework and a Plan-Do-Study-Act approach, the project implemented and evaluated a series of interventions. In the ‘PLAN’ phase, clinicians participated in a workshop to raise awareness of SEM challenges and inform the development of screening questions to support routine SEM assessment. The ‘DO’ phase involved implementing routine SEM screening during a 3 month trial, supported by active measures such as project champions, weekly reminders and team discussions to encourage sustained practice. The ‘STUDY’ phase included analysis of assessment outcome letters from three time points (baseline, trial and outcome retention phases) to evaluate changes in documentation and the sustainability of improvements. In the ‘ACT’ phase, findings were shared with the team, resulting in improved signposting, targeted recommendations and ongoing collaborations with feeding clinics. Findings demonstrated increased documentation of SEM challenges in assessment letters, with mentions rising from 33% at baseline to 71.9% during the trial and 64.3% in the retention phase. However, actionable recommendations and interventions remained limited during the trial but showed improvement in the retention phase, where letters included more tailored guidance and specific advice for SEM challenges. This project highlights the prevalence of SEM challenges among young people with neurodevelopmental movement disorders and underscores the importance of routine SEM screening. Developing standardised assessment tools and protocols could further aid clinicians in identifying and addressing these challenges during initial assessments.

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.

A review of the lPlease check whether the names of all authors are correct. iterature was conducted with the aim to understand whether a diagnosis of a tic disorder equated to higher levels of anxiety, and how this relationship varied when considering co-occurring attention deficit hyperactivity disorder (ADHD), autism and/or obsessive–compulsive disorder (OCD). A total of 25 studies were examined which highlighted children and adolescents with a tic disorder commonly met the criteria for a clinical anxiety disorder. While tic severity was found to be associated with higher levels of symptoms of anxiety in both children and adolescents with Tourette Syndrome (TS) or Chronic Tic Disorder (CTD), even higher levels of anxiety have been found in individuals who had an additional co-occurring diagnosis. For example, the diagnosis of having a tic disorder with OCD was more frequently associated with internalising disorders (e.g., anxiety, depressive, and somatic symptoms), whereas a diagnosis of a tic disorder and ADHD was commonly associated with externalising disorders (e.g., impulsivity disruptive conduct, substance use, and other addictive behaviours). Further studies are needed to address gender differences in anxiety, as anxiety is likely to be more prevalent in females with a tic disorder compared to both males and those with a later age of onset of tics. This review highlights the benefits of routinely screening for anxiety in children and adolescents with tics disorders, as well as the need for further considerations on how current treatments could be modified to help with anxiety and co-occurring diagnoses.

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.

OBJECTIVE:This is the first study to systematically explore the lived experiences of sudden and new onset of severe functional tics from the perspective of the mother's experiences and describes their attempts to access support services in the United Kingdom. METHOD:Twenty-One mothers of young people aged between 12 to 17 years with functional tic-like behaviour (FTLB) took part in semi-structured interviews. Thematic analysis of the transcribed interviews revealed gaps and inconsistencies within the process of gaining access to professional services and a lack of support for the management of tics and functional tic-like movements, in addition to highlighting the impact it had on daily family life. RESULTS:The themes generated included the occurrence and development of tics, the severity and intensity of symptoms, the psychological impact on the family and the need to make recommendations for a clear care pathway. Managing the impact of the FTLB and co-occurring conditions such as suicidal ideation and self-harm, as well as the physical and emotional trauma, commonly contributed to feelings of isolation and helplessness, which impacted negatively on the family's ability to function and participate in society. CONCLUSIONS:The findings emphasize the urgent need to create a clear management pathway for those experiencing FTLB, including the need for more professionals with relevant knowledge, to improve the dialogue with families during the referral process, whilst prioritising the treatment of anxiety and other identified mental health concerns.

BackgroundThis case series highlights the connection between childhood intense imagery movements (IIM) and adult-reported maladaptive daydreaming (MD). Motor stereotypies occur in typically developing children and also with co-occurring neurodevelopmental differences. A subgroup with complex motor stereotypies reports accompanying intense imagery, often enhanced by the movements. This phenomenon can persist into adulthood and, in some cases, will need active management to prevent significant distress and impairment.CasesSix adults, self-reporting maladaptive daydreaming associated with stereotypies, are presented to demonstrate the associations.Literature ReviewThe clinical significance and function of IIM and MD are unclear, but several hypotheses are discussed, including the mechanism of emotional regulation through sensory seeking, as a process for processing childhood psychological trauma, as intrusive thoughts or images as part of a subtype of Obsessive Compulsive Disorder, or as a result of diverse attentional networks seen in neurodevelopmental disorders.ConclusionsThis paper highlights important connections between IIM and MD. Many adults with MD show a childhood origin of stereotypical movements. Whilst immersive daydreaming may provide creativity and emotional regulation, there is evidence of distress and impairment of function for some adults, leading to MD diagnoses. Recognizing this phenomenon is important for all neurologists and physicians working with stereotypical movements.

The most widely applied diagnostic criteria for Tourette syndrome (TS) and other persistent motor and vocal tic disorders (PMVTD) are those included in the Diagnostic and Statistical Manual (DSM) of Mental Disorders of the American Psychiatric Association.1 These criteria have remained substantially unchanged for the past 30 years since the DSM-IV was published in 1994.2 DSM-IV and DSM-5-text revised (TR) criteria for primary tic disorders (Table 1) have set clear diagnostic standards for tic disorders. However, an increasingly shared view among experienced clinicians is that these criteria neither reflect the critical thinking behind the diagnosis of tic disorders nor the neurobiology of these conditions. Moreover, the current criteria may fail to separate neurobiological different conditions also manifesting with tics and tic-like behaviors. The broad inclusivity of the current criteria has been a longstanding problem that became more pressing with the sharp rise in functional tic-like behaviors (FTLBs) during the coronavirus disease 2019 pandemic.3-5 According to the DSM-5-TR,1 many individuals affected by FTLBs meet the criteria for and can formally be diagnosed with TS. There are serious risks related to this misdiagnosis, including unnecessary investigations, delayed treatment, and unwarranted, possibly harmful interventions. Additionally, some individuals with TS may subsequently develop concurrent FTLBs,6 which complicates management if not accurately recognized. Inaccurate diagnostic criteria can compromise the validity and reproducibility of research findings. Finally, misdiagnosis enhances stigma, leading to social isolation, discrimination, psychological distress, and erosion of trust in healthcare systems.7 In response to the growing number of adolescents and young adults seeking care for disabling FTLBs, an international working group collaborating with the European Society for the Study of Tourette Syndrome (ESSTS) has developed, through Delphi methodology, consensus-based criteria for a clinical diagnosis of FTLBs.8 These constitute a helpful tool for health professionals to diagnose and treat this condition with confidence.9-11 FTLBs display typical features of functional neurological symptoms12, 13 and have been demonstrated not to respond to the typical pharmacological therapy for primary tic disorders.14 Moreover, both conditions may benefit from treatment of psychiatric comorbidities and cognitive behavioral therapy.15 Given the clinical and pathophysiological differences between tics and FTLBs and the potential ambiguity of the current diagnostic criteria for primary tic disorders, we believe it is time to reconsider these criteria. In proposing this revision of diagnostic criteria for primary tic disorders, we have taken into account the key features distinguishing primary tic disorders from a pure FTLB disorder, with the aim of minimizing risk of misdiagnosis and inappropriate management. The DSM criteria for the diagnosis of tic disorders have changed from the different versions of the manual.16 The DSM is a product of the American Psychiatric Association's Committee on Nomenclature on Statistics and, historically, had a role in classifying psychiatric conditions into a clinical and medical framework. Both the original version and subsequent revisions reflected the social understanding of diseases at the time, and the evolving understanding shaped the classification.17 As a result, the modifications of the criteria for tic disorders over time were not informed by new evidence of the biological underpinnings of tic disorders. The most recent DSM-5-TR criteria rest on four pillars: (1) presence of vocal (phonic) and/or motor tics; (2) age at onset; (3) duration of tics; and (4) exclusion of secondary etiologies for tics. The criteria then differentiate TS from other persistent tic disorders based on the co-occurrence of motor and phonic tics. A strength of the DSM-5-TR classification is having included tic disorders in the category of "neurodevelopmental disorders," also comprising intellectual disability, communication disorders, autism spectrum disorder, and attention-deficit/hyperactivity disorder (ADHD), in line with the current, biology-driven conceptualization of tic disorders. Although specifically referring to tic disorders, the DSM-5-TR criteria do not consider impairment, whereas not all tics are functionally impairing and, therefore, the threshold for tics representing a disorder can be arbitrary. Overall, relevant limitations of the DSM-5-TR criteria should be highlighted, pertaining to four main themes. Because of these limitations, we believe these criteria do not accurately reflect the natural history of primary tic disorders and may fail to differentiate primary tic disorders from FTLBs accurately. The upper age limit of tic disorders onset has been controversial for decades. Although the DSM-III,18 without clear biological justification, first set the upper limit at age 15, the DSM-III-TR19 changed it to age 21. Eventually, again without a neurobiological rationale, this was modified to age 18 in the DSM-IV without subsequent modifications. The onset of TS is between age 4 and 8, whereas that of PMVTD is ~2 years later.20-24 Freeman et al.25 reported that 93% of 3500 TS participants exhibited tics before 10 years of age. Unlike previous versions, the 11th revision of the International Classification of Diseases (ICD-11) by the World Health Organisation26 does not include any specific age limit in the "essential" diagnostic criteria. However, among "course features," age of onset "commonly…between the ages of 4 and 6" is specified. Considering this natural history data, the current upper limit of 18 years for age at onset of primary tic disorders appears not well justified. Keeping this upper limit unchanged or eliminating altogether the age at onset criteria (as implied in the ICD-11 criteria) may dangerously increase the risk of misdiagnosis between primary tic disorders and FTLBs. The latter is typically present after the age of 12, as demonstrated by recent literature9 and stated in the ESSTS 2022 diagnostic criteria.8 To use age at onset as a supportive diagnostic criterion that reflects the actual time course of primary tic disorders, the upper limit of age at onset should be anticipated to be 10 to 12 years of age. Introducing this as a supportive, rather than mandatory, criterion would prevent a potential, and not uncommon, recall bias in self-reporting age at onset from erroneously ruling out the diagnosis of primary tic disorder. In TS and other PMVTD, initial tics are, in the majority of cases, simple tics involving the face, head, and/or neck regions.27, 28 During the following years of the developmental period, more complex tics or tics affecting other body regions may arise.28 Tics typically peak in severity between age 10 and 1420, 21 and decrease in severity over the course of mid-to-late adolescence,21, 29 although tics remit in adulthood in 10% to 20% of individuals.20 An increase in female proportion of the TS population with increasing age has also been observed, and potential differences in clinical course of TS between sexes were reported, which need further investigation.30 Conversely, the natural history of FTLBs differs substantially from that of primary tic disorders. Indeed, FTLBs often emerge abruptly in adolescents or young adults, with maximum disability often reached within the initial weeks, presenting from the outset with vocalizations and complex movements involving multiple body regions, predominantly limbs and torso.8-10 Despite being routinely considered in clinical practice and contributing significantly to the diagnostic process, these basic clinical features of tics are not included in current diagnostic criteria. We propose that early predominance of the cranial and cervical regions and early predominance of simple over complex tics should be included as supportive criteria of primary tic disorders. The current DSM-5-TR criteria specify a minimum 1-year disease duration to define a persistent tic disorder, whereas symptoms of less than 12 months' duration constitute a diagnosis of "Provisional Tic Disorder". Although the 1-year cut off aligns with the definition of "chronic disease" of the National Center for Chronic Disease Prevention and Health Promotion of the Center for Disease Control and Prevention (https://www.cdc.gov/chronicdisease/about/index.htm) and we consider this criterion acceptable, we acknowledge that it remains arbitrary. In fact, limited evidence suggests that most children with provisional tics may continue to exhibit tics for more than a year.31 However, at the present time, we lack prospective data suggesting the existence of an earlier cut point that would identify persistent tics as efficiently as the 12-months one. It has long been suggested that the differentiation between motor and phonic tics is arbitrary.32-34 Phonic tics are motor tics that involve the oral, nasal, pharyngeal, laryngeal, and respiratory musculature, resulting in the production of an audible sound. Both are often preceded by a premonitory urge, are highly suggestible, are usually suppressible, and may be exacerbated by stress or emotions. Of note, the term vocal tics is used interchangeably with phonic tics, but more accurately conveys tics that make sound because of the involvement of the vocal cords. In most cases, phonic tics do not involve the vocal cords, but the passage of air through the upper respiratory tract eventually produces their sound (ie, throat clearing or sniffing). Although commonalities and differences in the neurobiological basis of motor and phonic tics warrant further investigation, there is no evidence from registry-based and observational studies to support a different prognosis of a tic disorder based on the predominance of motor rather than phonic tics. Overall, although they communicate broad clinical categories of tic presentations, there is insufficient evidence to support a net separation between persistent motor tic disorder and persistent vocal (phonic) tic disorder. In addition, this separation may not be helpful in distinguishing between primary tic disorders and pure FTLBs, which too can present with different motor and vocal phenomena that wax and wane over time. Even the complexity of vocalizations is not helpful, as coprolalia is commonly noted among FTLBs.35 Among the important modifications to the DSM, echolalia, suppressibility of tics, fluctuation of symptoms, and impact on daily life activities were all initially proposed as criteria, but subsequently dropped in later editions of the DSM.19 However, the bedrock of the distinction between TS and other PMVTD has always been that motor and phonic tics must co-exist (although not necessarily concurrently or consistently) to diagnose TS. In particular, the DSM-5-TR criteria for TS specify that individuals must experience a combination of a minimum number of tics (ie, at least one phonic and two motor). However, patients with any form of primary persistent tic disorder, including TS, normally experience a much broader and fluid repertoire of tics, which can change widely over time. In keeping with this, the current ICD-11 criteria do not specify the number of required tics. Growing evidence suggests that, rather than distinct clinical entities, TS and PMVTD represent different degrees of severity or impairment of the same underlying condition.36 TS and PMVTD have clinically indistinguishable features, including onset in early childhood, response to the same treatments, waxing and waning clinical course, frequent improvement with age, family history, and comorbidity profile. Although our understanding of the genetic factors contributing to tic disorders is still limited, genome-wide association studies support that TS and PMVTD have a shared genetic profile and represent a continuous spectrum of condition, further reinforcing the diagnostic amalgamation of these two conditions.37 Although patients with TS have greater tic severity and slightly younger age at onset, both TS and PMVTD patients exhibit a high prevalence of psychiatric co-occurring conditions, including obsessive-compulsive disorder (OCD), ADHD, anxiety, and mood disorders.36 As in TS, co-occurring OCD and ADHD in PMVTD predict a higher incidence of maladaptive behaviors.38 This diagnostic differentiation appears, therefore, poorly substantiated. The similarity in comorbidity profile across all primary persistent tic disorders is, on the other hand, in contrast with the difference in frequency of comorbid neurodevelopmental and psychiatric disorders between primary tic disorders and pure FTLBs, with the latter showing greater prevalence of depression, anxiety disorders and, possibly, autism spectrum disorder.9 A unifying corollary to the above considerations is that the categorization of the "primary persistent tic disorder" into different diagnoses or clinical entities is not supported by evidence and has been challenged by the recently increased experience of FTLBs. Keeping the separation among TS, persistent motor tic disorder, and persistent phonic/vocal tic disorder could also perpetuate a stigmatizing divide between TS and non-TS tic disorders that is neither clinically nor neurobiologically justified. We, therefore, propose that the community of clinicians, scientists, and persons with lived experience should join forces to reappraise existing diagnostic criteria and establish a single diagnostic entity identified as primary persistent tic disorder (or other conceptually similar terminology). The key proposed changes are summarized in Table 1. Whether a neutral term will one day be preferred to the use of the TS eponym will require a more detailed risk–benefit analysis, inclusive of impact on stigma and care, patient perspective, as well as research in underdeveloped regions, and is, therefore, beyond the scope of this viewpoint. The lack of in vivo biomarkers and neuropathologic criteria for primary persistent tic disorder currently limit clinicians and scientists to an exclusively clinical definition. Therefore, any proposed revision of clinical criteria will need to be contrasted with newly identified markers when available. We believe that this proposal of revision to the current diagnostic criteria simplifies and provides more clarity to the nosology of primary tic disorders, while offering a diagnostic framework that can limit misdiagnosis and inappropriate management decisions that may occur in routine clinical practice, particularly with respect to pure FTLBs. 1. Research project: A. Conception, B. Organization, C. Execution; 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3. Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. M.S.: 1A, 1C, 3A; J.F.: 3B C.G.: 3B D.L.G.: 3B A.H.: 3B T.H.: 3B D.I.: 3B I.M.: 3B J.M.M.: 3B A.M.E.: 3B K.R.M.V.: 3B M.O.: 3B M.P.: 3B H.S.: 3B K.Ś.: 3B N.S.: 3B K.T.: 3B Y.W.: 3B T.P.: 1B, 3B D.M.: 1A, 1C, 3B M.S. is employed by King's College Hospital National Health Service (NHS) Trust. J.F. received honoraria from The New England Journal of Medicine: Clinical Neurology Update and American Academy of Neurology Course Presenter; and received grants from TAA Young Investigator Award. C.G. is employed by the University of Toronto; has received honoraria from the Movement Disorders Society; and has received grants from VolkswagenStiftung. D.G. provided consultancies to PTC Therapeutics and Emalex Biosciences; is employed by the Cincinnati Children's Hospital Medical Center; received honoraria from Illumina, PTC Therapeutics; received royalties from Elsevier, Wolters Kluwer; and received grants to the Institution of the United States (US) National Institute of Mental Health, US Department of Defense, Clinical Trials site investigator PTC Therapeutics, and Emalex Biosciences. A.H. provided consultancies to Noema Pharma; belongs to the advisory board of Association Française pour le syndrome Gilles de la Tourette; and is employed by Assistance Publique des Hôpitaux de Paris. T.H. is employed by GSTT and Kings College London, Faculty of Life Sciences and Medicine, Department of Women and Children's Health, London United Kingdom. D.I. belongs to the advisory board of Tourette Association of America; is employed by Vanderbilt University Medical Center; received honoraria from Tourette Association of America; received grants from National Institute of Neurological Disorders and Stroke (NINDS) (K23NS131592), Teva Branded Pharmaceutical Products, and R&D. I.M. provided consultancies to AbbVie; is employed by the University of Florida; received honoraria from the Tourette Association of America, Parkinson Foundation, Medscape, Efficient CME, and Cleveland Clinic; received royalties from Robert Rose publishers; received grants from the Parkinson Foundation, Tourette Association, Dystonia Coalition, AbbVie, Boston Scientific, Eli Lilly, Neuroderm, and Revance. J.M.M. is employed by Wake Forest University Health Sciences; received honoraria from the Movement Disorders Society, American Academy of Neurology; received grants from the Tourette Association of America, American Board of Psychiatry and Neurology, and NINDS NeuroNEXT. A.M.E. is employed by Horizon Health Network, New Brunswick, Canada. K.M.V. provided consultancies to Abide Therapeutics, adjupharm, Alexion, AMP Alternative Medical Products, Becanex, Boehringer Ingelheim International, Bionorica Ethics, CannaMedical Pharma, Canopy Grouth, Columbia Care, CTC Communications, Demecan, Enua pharma, DHMS Direct Health Medical Services, Ethypharm, Eurox Group, Global Praxis Group, Hormosan Pharma, Lundbeck, Marry Jane, MCI Germany, Neuraxpharm, Noema Pharma, Sanity Group, Stadapharm, Synendos Therapeutics AG, Syqe, Tilray, and Zambon; belongs to the advisory boards of Alexion, Branchenverband Cannabiswirtschaft e.V., CannaMedical Pharma, Bionorica Ethics, Canopy Growth, Columbia Care, Ethypharm, Hormosan Pharma, IMC Germany, Leafly Deutschland, Neuraxpharm, Sanity Group, Stadapharm, Synendos Therapeutics AG, Syqe Medical, Therapix Biosciences, and Tilray; received honoraria from Agaplesion Frankfurter Diakonie Kliniken gemeinnützige, Almirall, Aphria Deutschland, Arbeitsgemeinschaft Cannabis als Medizin, Astra Zeneca, Bedrocan, Bundesverband pharmazeutischer Cannabinoidunternehmen, Camurus, canymed, CEREBRO SPAIN BIDCO S.L, Cogitando, Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde, Diplomado Internacional de Endocannabinología (Programa Universitario de Investigación en Salud—PUIS, UNAM), Dresden International University, Emalex, EpiCampusNord, Eurox Deutschland, Ever pharma, Four20 Pharma, Georgia Medical Cannabis Project, Grow Group PLC, Hessische Landesstelle für Suchtfragen e.V., Landschaftsverband Westfalen-Lippe, LIO Pharmaceuticals, Medizinischer Dienst Westfalen Lippe, Meinhardt Congress, PR Berater, Salus—Fachklinikum Bernburg, Spectrum Therapeutics, streamedup!, Swiss Alpinopharm, SynopticCon, targoEvent, Takeda, Tilray, VFnK—Verein zur Förderung neurologisch Kranker e.V., von Mende Marketing, Wayland Group, and WeCann; received royalties from Deutsches Ärzteblatt, Der Neurologie und Psychiater, Elsevier, Medizinisch Wissenschaftliche Verlagsgesellschaft Berlin, and Kohlhammer; and received grants from German Research Foundation, German Federal Ministry of Education and Research, Tourette Gesellschaft Deutschland e.V., Else-Kröner-Fresenius-Stiftung, and Almirall. M.S.O. is employed by Medical Advisor, Parkinson's Foundation; received honoraria from The Movement Disorders Society, American Academy of Neurology, Vanderbilt University, WebMD/Medscape; received royalties from Books4Patients; received grants from National Institutes of Health (NIH), The Michael J. Fox Foundation, and Tourette Association of America. M.P. provided consultancies to GuidePoint Global and Orphalan; belonged to the advisory board of Teva; employed by Baylor College of Medicine; received honoraria from The Movement Disorders Society; and received grants from Clinical trial support from NIH, PTC Therapeutics, Alexion, and Neurocrine Biosciences. H.S. provided consultancies to Novo Nordisk; received honoraria from The Movement Disorder Society and American Academy of Neurology; and received grants from Clinical trial support from Novo Nordisk, Blue Rock, Neuroderm, Prevail, Bukwang, Genentech, Biogen, MeiraGTX, Sun Pharma, NIH, and Insightec. K.S. is employed by the 5th Regional Hospital, Sosnowiec, Poland; received honoraria from AbbVie and Orphalan; and received grants supported by the Brain Disease Foundation. N.S. is employed by the University of Calgary; and received grants supported by an American Academy of Neurology Fellowship grant, American Brain Foundation, and Tourette Association as well as Polish Ministry of Health, and travel grant from the International Movement Disorders Society. Y.W. is employed by King's College Hospital NHS Trust. K.T. provided consultancies to Emalex; is employed by Boston Children's Hospital; and received grants from Toretta-Lee Family. T.P. is employed by the University of Calgary; and received grants from The Canadian Institutes of Health Research and the Azrieli Accelerator. D.M. provided consultancies to Roche; belonged to the advisory board of Merz Pharmaceuticals; is employed by the University of Calgary; received honoraria from Dystonia Medical Research Foundation Canada, Movement Disorders Society, Canadian Movement Disorders Society; received royalties from Springer-Verlag, Oxford University Press; and received grants from Neuroscience, Rehabilitation, and Vision Strategic Clinical Network of the Alberta Health Services, Owerko Foundation, Dystonia Medical Research Foundation (DMRF) USA, DMRF Canada, and National Spasmodic Torticollis Association Sacramento Chapter in Memory of Howard Thiel, Parkinson Canada, The Canadian Institutes of Health Research, and Michael P. Smith Family. The data that support the findings of this study are available from the corresponding author upon reasonable request.

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.

people with FTLBs are well-supported with the use of certain techniques, they can manage 66 well at school.There is strong evidence demonstrating that individuals with tic disorders experience a lower 68 quality of life, with tics shown to have a pervasive impact on all aspects of daily living (4). Obsessive-compulsive disorder and tic disorders can often co-occur, with individuals fre-84 quently presenting with distinct symptoms of CTD and/or OCD (5). However, there are also a 85 subset of individuals with a condition which has been referred to as Tourettic OCD (TOCD),where patients show a specific overlap in tics, compulsions, and their preceding premonitory