Tourette Syndrome: A Catalyst for Operationalizing Neurodiversity.

Our goal, taking Tourette syndrome as a case example, is to introduce neurologists to, and motivate discussion on, the neurodiversity paradigm. This philosophical construct considers some neurologic conditions in diversity, instead of simply disease. Moving from philosophical idea to empirical construct draws from patient and family perspectives on (1) quality of life and discrimination, (2) disability pride, and (3) unique profiles of different patient cohorts. Listening to patient voices, attending to family, advocacy group, and societal views on neurologic disorders can strengthen precision neurology practice. Dialogs on neurodiversity, including antitherapy sentiments, offer to enhance neurologic care, patient agency, and autonomy; encourage respectful communications with patients who challenge the idea their condition is pathologic; and to set the stage for future empirical investigations and practice guidelines.

Structural Variants and Implicated Processes Associated with Familial Tourette Syndrome.

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental psychiatric disorder with complex and elusive etiology with a significant role of genetic factors. The aim of this study was to identify structural variants that could be associated with familial GTS. The study group comprised 17 multiplex families with 80 patients. Structural variants were identified from whole-genome sequencing data and followed by co-segregation and bioinformatic analyses. The localization of these variants was used to select candidate genes and create gene sets, which were subsequently processed in gene ontology and pathway enrichment analysis. Seventy putative pathogenic variants shared among affected individuals within one family but not present in the control group were identified. Only four private or rare deletions were exonic in LDLRAD4, B2M, USH2A, and ZNF765 genes. Notably, the USH2A gene is involved in cochlear development and sensory perception of sound, a process that was associated previously with familial GTS. In addition, two rare variants and three not present in the control group were co-segregating with the disease in two families, and uncommon insertions in GOLM1 and DISC1 were co-segregating in three families each. Enrichment analysis showed that identified structural variants affected synaptic vesicle endocytosis, cell leading-edge organization, and signaling for neurite outgrowth. The results further support the involvement of the regulation of neurotransmission, neuronal migration, and sound-sensing in GTS.

Case Report: Second-order Contrast Sensitivity in Tourette Syndrome. / Olgu Sunumu: Tourette Sendromunda Ikinci Düzey Kontrast Duyarliligi.

disease, characterized by motor and vocal tics with no changes in the ocular structures in the ophthalmological evaluations. The visual field evaluations suggest a reduction in central visual field sensitivity. The studies on visual function in this population is scarce. In this case report we present a patient with GTS who has significant alterations in the measure of contrast sensitivity for second order vision without any vision complaints. This reduction occurred in the measure of contrast sensitivity with a white noise carrier for practically all tested space frequencies. The mean contrast sensitivity for first and second-order stimuli with a pink-noise carrier was normal. The second order contrast sensitivity with a white noise carrier is dependent on local and lateral inhibition since it includes many local luminance components. The existence of this sensitivity suggests that specific visual processing mechanisms are affected. Keywords: Tourette Syndrome, Contrast Sensitivity, Contrast Psychophysical Channels, Second-Order Perception.

Neural representations of statistical and rule-based predictions in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (GTS) is a disorder characterised by motor and vocal tics, which may represent habitual actions as a result of enhanced learning of associations between stimuli and responses (S-R). In this study, we investigated how adults with GTS and healthy controls (HC) learn two types of regularities in a sequence: statistics (non-adjacent probabilities) and rules (predefined order). Participants completed a visuomotor sequence learning task while EEG was recorded. To understand the neurophysiological underpinnings of these regularities in GTS, multivariate pattern analyses on the temporally decomposed EEG signal as well as sLORETA source localisation method were conducted. We found that people with GTS showed superior statistical learning but comparable rule-based learning compared to HC participants. Adults with GTS had different neural representations for both statistics and rules than HC adults; specifically, adults with GTS maintained the regularity representations longer and had more overlap between them than HCs. Moreover, over different time scales, distinct fronto-parietal structures contribute to statistical learning in the GTS and HC groups. We propose that hyper-learning in GTS is a consequence of the altered sensitivity to encode complex statistics, which might lead to habitual actions.

Comparison of children and adults in deep brain stimulation for Tourette Syndrome: a large-scale multicenter study of 102 cases with long-term follow-up.

BACKGROUND: Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. METHODS: This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive-compulsive disorder (OCD), depression, and quality of life, respectively. RESULTS: Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). CONCLUSIONS: DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

[Deep Brain Stimulation for Tourette's Syndrome and Challenging for Neuropsychiatric Disease].

The efficacy of deep brain stimulation(DBS)for Tourette's syndrome is being well established. Herein, we performed DBS in 38 patients and confirmed that its efficacy was comparable with that reported internationally. Although many patients experience severe symptoms, the indications for surgery remain controversial. One reason for this is that Tourette syndrome has the potential for spontaneous remission, while DBS treatment results in the need for long-term management, which can be difficult for some patients. Furthermore, while several targets for DBS have been reported, no treatment guidelines have yet been established. The efficacy of DBS for neuropsychiatric disorders, such as obsessive-compulsive disorder, depression, and dementia, is gradually being reported. However, this use has many limitations in terms of expectations similar to those seen with Tourette's syndrome, leading to problems with expanding indications for these disorders. Indications for these disorders should be addressed in conjunction with ethical issues. It is expected that more data on this topic will be collected in the future.

Internet-Delivered Exposure and Response Prevention for Pediatric Tourette Syndrome: 12-Month Follow-Up of a Randomized Clinical Trial.

Importance: Behavior therapy is a recommended intervention for Tourette syndrome (TS) and chronic tic disorder (CTD), but availability is limited and long-term effects are uncertain. Objective: To investigate the long-term efficacy and cost-effectiveness of therapist-supported, internet-delivered exposure and response prevention (ERP) vs psychoeducation for youths with TS or CTD. Design, Setting, And Participants: This 12-month controlled follow-up of a parallel group, superiority randomized clinical trial was conducted at a research clinic in Stockholm, Sweden, with nationwide recruitment. In total, 221 participants aged 9 to 17 years with TS or CTD were enrolled between April 26, 2019, and April 9, 2021, of whom 208 (94%) provided 12-month follow-up data. Final follow-up data were collected on June 29, 2022. Outcome assessors were masked to treatment allocation throughout the study. Interventions: A total of 111 participants were originally randomly allocated to 10 weeks of therapist-supported, internet-delivered ERP and 110 participants to therapist-supported, internet-delivered psychoeducation. Main Outcomes And Measures: The primary outcome was within-group change in tic severity, measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS), from the 3-month follow-up to the 12-month follow-up. Treatment response was defined as 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement scale. Analyses were intention-to-treat and followed the plan prespecified in the published study protocol. A health economic evaluation was performed from 3 perspectives: health care organization (including direct costs for treatment provided in the study), health care sector (additionally including health care resource use outside of the study), and societal (additionally including costs beyond health care [eg, parent's absenteeism from work]). Results: In total, 221 participants were recruited (mean [SD] age, 12.1 [2.3] years; 152 [69%] male). According to the YGTSS-TTSS, there were no statistically significant changes in tic severity from the 3-month to the 12-month follow-up in either group (ERP coefficient, -0.52 [95% CI, -1.26 to 0.21]; P = .16; psychoeducation coefficient, 0.00 [95% CI, -0.78 to 0.78]; P > .99). A secondary analysis including all assessment points (baseline to 12-month follow-up) showed no statistically significant between-group difference in tic severity from baseline to the 12-month follow-up (coefficient, -0.38 [95% CI, -1.11 to 0.35]; P = .30). Treatment response rates were similar in both groups (55% in ERP and 50% in psychoeducation; odds ratio, 1.25 [95% CI, 0.73-2.16]; P = .42) at the 12-month follow-up. The health economic evaluation showed that, from a health care sector perspective, ERP produced more quality-adjusted life years (0.01 [95% CI, -0.01 to 0.03]) and lower costs (adjusted mean difference -$84.48 [95% CI, -$440.20 to $977.60]) than psychoeducation at the 12-month follow-up. From the health care organization and societal perspectives, ERP produced more quality-adjusted life years at higher costs, with 65% to 78% probability of ERP being cost-effective compared with psychoeducation when using a willingness-to-pay threshold of US $79 000. Conclusions And Relevance: There were no statistically significant changes in tic severity from the 3-month through to the 12-month follow-up in either group. The ERP intervention was not superior to psychoeducation at any time point. While ERP was not superior to psychoeducation alone in reducing tic severity at the end of the follow-up period, ERP is recommended for clinical implementation due to its likely cost-effectiveness and support from previous literature. Trial Registration: ClinicalTrials.gov Identifier: NCT03916055.

The effects of Shaoma Zhijing granules and its main components on Tourette syndrome.

BACKGROUND: Tourette syndrome (TS) represents a neurodevelopmental disorder characterized by an uncertain etiology and influencing factors. Frequently, it co-occurs with conditions such as attention deficit hyperactivity disorder, obsessive-compulsive disorder, and sleep disturbances, which have garnered substantial attention from the research community in recent years. Clinical trials have demonstrated that Shaoma Zhijing Granules (SMZJG, 5-ling granule, also known as TSupport or T92 under U.S. development), a traditional Chinese medicine compound, is an effective treatment for TS. PURPOSE: To conduct scientometric analysis on developing trends, research countries and institutions, current status, hot spots of TS and discuss the underlying mechanisms of SMZJG and its main components on TS. The aim is to provide valuable reference for ongoing clinical and basic research on TS and SMZJG. STUDY DESIGN & METHODS: Using Tourette syndrome, SMZJG and its main components along with their synonyms as keywords, we conducted a comprehensive search across major scientific databases including the Web of Science Core Collection, PubMed and China National Knowledge Infrastructure (CNKI) databases. A total of 5952 references and 99 patents were obtained. Among these, 5039 articles and reviews, as well as 54 patents were analyzed by Citespace and VOSviewer software. RESULTS: The available evidence indicates that the SMZJG's components likely exert their mechanisms in treating TS by regulating the dopaminergic pathway system, neurotransmitter imbalances, reducing neuroinflammation, promoting the repair of nerve damage and improving sleep disorders. CONCLUSION: This comprehensive analysis lays the foundation for an extensive exploration of the feasibility and clinical applications of SMZJG in TS treatment.

Rapid Compensation for Noisy Voluntary Movements in Adults with Primary Tic Disorders.

BACKGROUND: It has been proposed that tics and premonitory urges in primary tic disorders (PTD), like Tourette syndrome, are a manifestation of sensorimotor noise. However, patients with tics show no obvious movement imprecision in everyday life. One reason could be that patients have strategies to compensate for noise that disrupts performance (ie, noise that is task-relevant). OBJECTIVES: Our goal was to unmask effects of elevated sensorimotor noise on the variability of voluntary movements in patients with PTD. METHODS: We tested 30 adult patients with PTD (23 male) and 30 matched controls in a reaching task designed to unmask latent noise. Subjects reached to targets whose shape allowed for variability either in movement direction or extent. This enabled us to decompose variability into task-relevant versus less task-relevant components, where the latter should be less affected by compensatory strategies than the former. In alternating blocks, the task-relevant target dimension switched, allowing us to explore the temporal dynamics with which participants adjusted movement variability to changes in task demands. RESULTS: Both groups accurately reached to targets, and adjusted movement precision based on target shape. However, when task-relevant dimensions of the target changed, patients initially produced movements that were more variable than controls, before regaining precision after several reaches. This effect persisted across repeated changes in the task-relevant dimension across the experiment, and therefore did not reflect an effect of novelty, or differences in learning. CONCLUSIONS: Our results suggest that patients with PTD generate noisier voluntary movements compared with controls, but rapidly compensate according to current task demands. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Emerging therapies for childhood-onset movement disorders.

PURPOSE OF REVIEW: We highlight novel and emerging therapies in the treatment of childhood-onset movement disorders. We structured this review by therapeutic entity (small molecule drugs, RNA-targeted therapeutics, gene replacement therapy, and neuromodulation), recognizing that there are two main approaches to treatment: symptomatic (based on phenomenology) and molecular mechanism-based therapy or 'precision medicine' (which is disease-modifying). RECENT FINDINGS: We highlight reports of new small molecule drugs for Tourette syndrome, Friedreich's ataxia and Rett syndrome. We also discuss developments in gene therapy for aromatic l-amino acid decarboxylase deficiency and hereditary spastic paraplegia, as well as current work exploring optimization of deep brain stimulation and lesioning with focused ultrasound. SUMMARY: Childhood-onset movement disorders have traditionally been treated symptomatically based on phenomenology, but focus has recently shifted toward targeted molecular mechanism-based therapeutics. The development of precision therapies is driven by increasing capabilities for genetic testing and a better delineation of the underlying disease mechanisms. We highlight novel and exciting approaches to the treatment of genetic childhood-onset movement disorders while also discussing general challenges in therapy development for rare diseases. We provide a framework for molecular mechanism-based treatment approaches, a summary of specific treatments for various movement disorders, and a clinical trial readiness framework.

Human mutations in high-confidence Tourette disorder genes affect sensorimotor behavior, reward learning, and striatal dopamine in mice.

Tourette disorder (TD) is poorly understood, despite affecting 1/160 children. A lack of animal models possessing construct, face, and predictive validity hinders progress in the field. We used CRISPR/Cas9 genome editing to generate mice with mutations orthologous to human de novo variants in two high-confidence Tourette genes, CELSR3 and WWC1. Mice with human mutations in Celsr3 and Wwc1 exhibit cognitive and/or sensorimotor behavioral phenotypes consistent with TD. Sensorimotor gating deficits, as measured by acoustic prepulse inhibition, occur in both male and female Celsr3 TD models. Wwc1 mice show reduced prepulse inhibition only in females. Repetitive motor behaviors, common to Celsr3 mice and more pronounced in females, include vertical rearing and grooming. Sensorimotor gating deficits and rearing are attenuated by aripiprazole, a partial agonist at dopamine type II receptors. Unsupervised machine learning reveals numerous changes to spontaneous motor behavior and less predictable patterns of movement. Continuous fixed-ratio reinforcement shows that Celsr3 TD mice have enhanced motor responding and reward learning. Electrically evoked striatal dopamine release, tested in one model, is greater. Brain development is otherwise grossly normal without signs of striatal interneuron loss. Altogether, mice expressing human mutations in high-confidence TD genes exhibit face and predictive validity. Reduced prepulse inhibition and repetitive motor behaviors are core behavioral phenotypes and are responsive to aripiprazole. Enhanced reward learning and motor responding occur alongside greater evoked dopamine release. Phenotypes can also vary by sex and show stronger affection in females, an unexpected finding considering males are more frequently affected in TD.

Symptom Severity and Health Impacts of Functional Tic-Like Behaviors in Youth.

BACKGROUND: We performed this study to improve understanding of the relationship between functional tic-like behaviors (FTLBs) and quality of life, loneliness, family functioning, anxiety, depression, and suicidality. METHOD: This cross-sectional study assessed self-reported quality of life, disability, loneliness, depression, anxiety, family functioning, tic severity, and suicide risk in age- and birth-sex matched youth with FTLBs, Tourette syndrome (TS), and neurotypical controls. We performed specific subanalyses comparing individuals with FTLBs who identified as transgender/gender diverse (TGD) with cisgender individuals. RESULTS: Eighty-two youth participated (age range 11 to 25, 90% female at birth), including 35 with FTLBs, 22 with TS, and 25 neurotypical controls. A significantly higher proportion of participants with FTLB identified as TGD (15 of 35) than TS (two of 22) and neurotypical control (three of 25) participants. Compared with neurotypical controls, individuals with FTLBs had significantly lower quality of life, greater disability, loneliness, social phobia, anxiety symptoms, depressive symptoms, and suicidality. Compared with individuals with TS, individuals with FTLBs had more school/work absences due to tics, had more depressive symptoms, were more likely to be at high risk for suicidality, and had disability in self-care and life activity domains. There were no significant differences between cisgender and TGD participants with FTLB in any of the domains assessed. CONCLUSIONS: Youth with FTLB have unique health care needs and associations with anxiety, depression, sex, and gender.

The Challenge of Examining Social Determinants of Health in People Living With Tourette Syndrome.

BACKGROUND: To examine the association between race, ethnicity, and parental educational attainment on tic-related outcomes among Tourette Syndrome (TS) participants in the Tourette Association of America International Consortium for Genetics (TAAICG) database. METHODS: 723 participants in the TAAICG dataset aged ≤21 years were included. The relationships between tic-related outcomes and race and ethnicity were examined using linear and logistic regressions. Parametric and nonparametric tests were performed to examine the association between parental educational attainment and tic-related outcomes. RESULTS: Race and ethnicity were collapsed as non-Hispanic white (N=566, 88.0%) versus Other (N=77, 12.0%). Tic symptom onset was earlier by 1.1 years (P < 0.0001) and TS diagnosis age was earlier by 0.9 years (P = 0.0045) in the Other group (versus non-Hispanic white). Sex and parental education as covariates did not contribute to the differences observed in TS diagnosis age. There were no significant group differences observed across the tic-related outcomes in parental education variable. CONCLUSIONS: Our study was limited by the low number of nonwhite or Hispanic individuals in the cohort. Racial and ethnic minoritized groups experienced an earlier age of TS diagnosis than non-Hispanic white individuals. Tic severity did not differ between the two groups, and parental educational attainment did not affect tic-related outcomes. There remain significant disparities and gaps in knowledge regarding TS and associated comorbid conditions. Our study suggests the need for more proactive steps to engage individuals with tic disorders from all racial and ethnic minoritized groups to participate in research studies.

A meta-analysis of transcranial magnetic stimulation in Tourette syndrome.

There is growing enthusiasm for the treatment of neuropsychiatric disorders using neuromodulation. While some reports claim that transcranial magnetic stimulation (TMS) can be used to treat Tourette Syndrome (TS), little research exists to support this assertion. This meta-analysis examined the efficacy of TMS to reduce tic severity in patients with TS. Additionally, it explored the effect of TMS to reduce premonitory urge severity-the primary mechanism implicated in the frontline evidence-based treatment of TS. Five treatment comparisons were selected using PRISMA guidelines. All studies included were required to be (1) a randomized controlled trial, (2) compare TMS to a sham condition, and (3) have all participants meet diagnostic criteria for a persistent tic disorder and/or TS. A random effects model meta-analysis examined the efficacy of using TMS to reduce tic severity and explored the effect of TMS to reduce premonitory urge severity. TMS did not significantly reduce tic severity (g = 0.44; 95% CI = -0.17, 1.05; z = 1.40; p = 0.16), but a moderate reduction in premonitory urge severity was found (g = 0.63; 95% CI = 0.9, 1.17; z = 2.27; p < 0.02). Trials with larger sample sizes and a preponderance of women were found to have greater therapeutic effects of TMS for tic severity. There is limited support for the use of TMS to reduce tic severity, though reductions in premonitory urge severity were observed. Major limitations of the existing literature are examined, with a call for research investigating newer TMS protocols and their use as a treatment augmentation strategy.

A qualitative study of Chinese parental perspectives on the causes of Tourette syndrome in children.

Parents' beliefs and attitudes toward their children with Tourette syndrome (TS) influence treatment-seeking behaviors. This study aimed to explore and describe the Chinese parents' perspectives on the causes of TS for their children. A qualitative study using semi-structured interviews was conducted with the parents of TS patients from a children's hospital in western China from June to July 2021, and thematic analysis was performed to transcribe interviews and identify themes. A total of 13 participants were interviewed in this study. Five themes were developed in relation to the cognition of the causes of TS in parents, including physical problems, parenting and education problems, mental problems, bad habits, and neurological problems. Due to the insufficient awareness of TS, most parents repeatedly seek medical advice that they regarded the symptoms as physical problems or neurological problems. They generally felt guilty and blamed themselves for their parenting styles and education methods. And some parents attributed it to the poor psychological quality or the bad habits of children. Study findings showed a lack of scientific understanding of the causes of TS among parents further hindered the timely effective treatment for patients and affected the family relationships, which highlights the importance of public education and raising awareness of the disease.

Responsive deep brain stimulation for the treatment of Tourette syndrome.

To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6 month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6 months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10 Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

Quantifying tics: Best practices and design considerations for video-based tic coding in research.

Tic disorders (TD), including Tourette Syndrome, are characterized by involuntary, repetitive movements and/or vocalizations that can lead to persistent disability and impairment across the lifespan. Existing research demonstrates that video-based behavioral coding (VBBC) methods can be used to reliably quantify tics, enabling a more objective approach to tic measurement above and beyond standardly used TD questionnaires. VBBC is becoming more popular given the ease and ubiquity of obtaining patient videos. However, rigor and reproducibility of this work has been limited by undescribed and unstandardized approaches to using VBBC methods in TD research. The current paper describes "best practices" for VBBC in TD research, which have been tested and refined in our research over the past 15+ years, including considerations for data acquisition, coding implementation, interrater reliability demonstration, and methods reporting. We also address ethical considerations for researchers using this method.

The role of neuroactive steroids in tic disorders.

Tics are sudden, repetitive movements or vocalizations. Tic disorders, such as Tourette syndrome (TS), are contributed by the interplay of genetic risk factors and environmental variables, leading to abnormalities in the functioning of the cortico-striatal-thalamo-cortical (CSTC) circuitry. Various neurotransmitter systems, such as gamma-aminobutyric acid (GABA) and dopamine, are implicated in the pathophysiology of these disorders. Building on the evidence that tic disorders are predominant in males and exacerbated by stress, emerging research is focusing on the involvement of neuroactive steroids, including dehydroepiandrosterone sulfate (DHEAS) and allopregnanolone, in the ontogeny of tics and other phenotypes associated with TS. Emerging evidence indicates that DHEAS levels are significantly elevated in the plasma of TS-affected boys, and the clinical onset of this disorder coincides with the period of adrenarche, the developmental stage characterized by a surge in DHEAS synthesis. On the other hand, allopregnanolone has garnered particular attention for its potential to mediate the adverse effects of acute stress on the exacerbation of tic severity and frequency. Notably, both neurosteroids act as key modulators of GABA-A receptors, suggesting a pivotal role of these targets in the pathophysiology of various clinical manifestations of tic disorders. This review explores the potential mechanisms by which these and other neuroactive steroids may influence tic disorders and discusses the emerging therapeutic strategies that target neuroactive steroids for the management of tic disorders.

Psychological Factors Associated with Functional Tic-like Behaviours during the COVID-19 Pandemic.

Functional tic-like behaviours (FTLB) are a female predominant functional neurological disorder that escalated in incidence during the SARS CoV2 pandemic. This study compared social and adaptive functioning, social media use, pandemic experiences, and psychiatric comorbidities between FTLB (n = 35), Tourette Syndrome (TS) (n = 22), and neurotypical (NT) (n = 25) participants ages 11 to 25 years. The psychiatric comorbidity burden for participants with FTLB was formidable, with frequencies ranging from 1.5 to 10 times higher for major depressive disorder and panic disorder compared to TS and NT participants. Borderline personality disorder (BPD), agoraphobia, social anxiety disorder, and generalized anxiety disorder were also significantly more common in FTLB compared to NT participants. Vulnerable attachment scores, social phobia and social interaction anxiety symptoms were higher in participants with FTLB than NT but not TS. Overall distress tolerance, resilient coping, suggestibility, hours on social media, and exposure to tic and TS content were not significantly different between groups. FTLB participants rated their mental health declined more severely during the pandemic than both TS and NT participants and were more likely to experience trouble sleeping, loneliness, and difficulty affording housing and food than NT participants. Participants with FTLB were significantly more likely to identify as gender minority people than TS and NT, though there were no significant differences based on gender identity in the study variables within the FTLB group. The association and potential pathways explaining how psychiatric disorders may be contributing to FTLB, and why certain groups appear at particular risk are discussed.