Cytokine expression profiles in children and adolescents with tic disorders.

The etiology of tic disorders (TDs) is not precisely known, although several lines of evidence suggest involvement of the immune system in pathogenesis. Here, we aimed to determine the expression levels of pro-inflammatory and anti-inflammatory cytokines in children with TD and compare them with those of healthy controls. Furthermore, we also evaluated their association with clinical variables in the TD group. Within the study period, 88 children with tic disorders and 111 healthy control children were enrolled. Most children with tic disorders were diagnosed with Tourette's disorder (n = 47, 53.4%) or persistent motor tic disorder (n = 39, 44.3%), while the remainder (n = 2, 2.3%) were diagnosed with persistent vocal tic disorder. We found that children with tic disorders had significantly elevated levels of IL-1ß, TNF-α, IL-6 and IL-4 expression, while we detected lower expression levels of IL-17 in children with tic disorders. Our findings provide a molecular landscape of cytokine expression in children with TD, which may suggest a proinflammatory state not affected by the presence of comorbidity and symptom severity. Delineating the contribution of alterations in the immune system to the pathogenesis of tic disorders may pave the way for better therapeutic interventions.

Effect of acupuncture on tic disorder: a randomized controlled clinical trial based on energy metabolomics and infrared thermography.

BACKGROUND: Acupuncture is a method for treating tic disorder. However, there is a lack of sufficient clinical objective basis in regards of its treatment efficacy. Indeed, there are structural abnormalities present in energy metabolism and infrared thermography in children with tic disorder. Therefore, this study proposes a clinical trial scheme to explore the possible mechanism of acupuncture in treating tic disorder. METHODS: This randomized controlled trial will recruit a total of 90 children, in which they will be divided into non-intervention group and intervention group. The non-intervention group consists of 30 healthy children while the intervention group consists of 60 children with tic disorder. The intervention group will be randomly allocated into either the treatment group or the control group, with 30 children randomly assigned in each group. Children either received acupuncture treatment and behavioral therapy (treatment group) or sham acupuncture treatment and behavioral therapy (control group), 3 treatment sessions per week for a period of 12 weeks, with a total of 36 treatment sessions. Outcome measures include YGTSS, urinary and fecal metabolomics, infrared thermography of body surface including governor vessel. For the intervention group, these outcome measures will be collected at the baseline and 90th day prior to intervention. Whereas for the non-intervention group, outcome measures (excluding YGTSS) will be collected at the baseline. DISCUSSION: The main outcome will be to observe the changes of the severity of tic condition, the secondary outcome will be to observe the changes of structural characteristic of infrared thermography of body surface/acupoints along the governor vessel and to evaluate the changes of urinary and fecal metabolomics at the end of the treatment, so as to analyze the relationship between them and to provide further knowledge in understanding the possible mechanism of acupuncture in improving the clinical symptoms via regulating and restoring the body metabolomics network, which in future it can develop as a set of clinical guideline (diagnosis, treatment, assessment, prognosis) in treating tic disorder. ChiCTR2300075188(Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 29 August 2023).

Aberrant Functional Connectivity of the Salience Network in Adult Patients with Tic Disorders: A Resting-State fMRI Study.

Tic disorders (TD) are characterized by the presence of motor and/or vocal tics. Common neurophysiological frameworks suggest dysregulations of the cortico-striatal-thalamo-cortical (CSTC) brain circuit that controls movement execution. Besides common tics, there are other "non-tic" symptoms that are primarily related to sensory perception, sensorimotor integration, attention, and social cognition. The existence of these symptoms, the sensory tic triggers, and the modifying effect of attention and cognitive control mechanisms on tics may indicate the salience network's (SN) involvement in the neurophysiology of TD. Resting-state functional MRI measurements were performed in 26 participants with TD and 25 healthy controls (HC). The group differences in resting-state functional connectivity patterns were measured based on seed-to-voxel connectivity analyses. Compared to HC, patients with TD exhibited altered connectivity between the core regions of the SN (insula, anterior cingulate cortex, and temporoparietal junction) and sensory, associative, and motor-related cortices. Furthermore, connectivity changes were observed in relation to the severity of tics in the TD group. The SN, particularly the insula, is likely to be an important site of dysregulation in TD. Our results provide evidence for large-scale neural deviations in TD beyond the CSTC pathologies. These findings may be relevant for developing treatment targets.

Exploring the psychometric properties of the premonitory urge for tics scale (PUTS) and its association with psychiatric symptoms in Chinese children with tic disorders.

BACKGROUND: The Premonitory Urge for Tics Scale (PUTS) is a common self-report measure of premonitory urges for patients with tic disorders. This study aims to evaluate the Chinese version of the PUTS (PUTS-C) and to explore its association with psychiatric symptoms in Chinese children diagnosed with tic disorders. METHODS: The psychometric evaluation involved 204 outpatients with tic disorders, aged 7-16 years, who were divided into two age groups: (7-10 years, n = 103; 11-16 years, n = 95). RESULTS: The PUTS-C demonstrated good internal consistency (McDonald'sω = 0.84) and two-week test-retest reliability (0.76). We observed a statistically significant correlation between the total PUTS-C score and various Yale Global Tic Severity Scale (YGTSS) subscales and total tic severity scores. The PUTS-C score also showed significant correlations with the Children Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Screening Child Anxiety-Related Emotional Disorders (SCARED), and Children's Depression Inventory (CDI). Notably, premonitory urges independently predicted tic severity, beyond the influence of comorbid symptoms. A two-factor structure of the PUTS-C was identified in the total sample through factor analysis. CONCLUSIONS: The PUTS-C possesses acceptable validity and good reliability. It appears that premonitory urges in Chinese patients with tic disorders are associated with obsessive-compulsive symptoms, anxiety, and depression, but can independently predict tic severity. Specific PUTS-C factors possibly related to motor and vocal tics. Future research should continue to investigate age-related differences and the association with tics and other sensory symptoms.

Perceived Negative Effects of Tic Management Strategies in Adults With Tic Disorders.

Behavior therapy is a well-established and empirically supported treatment for tic disorders (TDs). However, concerns have been expressed about the negative effects of behavioral interventions, such as tic worsening, tic substitution, and excessive effort. This study explored perceived negative effects of tic management strategies in adults with TDs and predictors of these experiences. Participants (N = 72) completed semi-structured interviews 11 years after receiving behavior therapy or supportive therapy in a randomized clinical trial. We examined responses to interview questions about managing tics and predictors of reported negative effects. Most participants did not experience tic worsening (84%) or tic substitution (75%) from tic management strategies. The majority felt they could manage tics while participating in their environment (87%) and did not report life interference from tic management (77%). About half (45%) felt less present when managing tics. Treatment non-responders in the original trial were more likely to report negative effects of tic management strategies. No differences in reported negative consequences were found between those who received behavior therapy versus supportive therapy, suggesting that behavior therapy specifically does not lead to such adverse effects. These findings could reduce misconceptions about behavior therapy for TDs and enhance its acceptability and utilization.

Screening for Quality of Life in a Neurology Tic Clinic Using Quality Improvement Methodology.

BACKGROUND: Tic disorders in children often co-occur with other disorders that can significantly impact functioning. Screening for quality of life (QoL) can help identify optimal treatment paths. This quality improvement (QI) study describes implementation of a QoL measure in a busy neurology clinic to help guide psychological intervention for patients with tics. METHODS: Using QI methodology outlined by the Institute for Healthcare Improvement, this study implemented the PedsQL Generic Core (4.0) in an outpatient medical clinic specializing in the diagnosis and treatment of tic disorders. Assembling a research team to design process maps and key driver diagrams helped identify gaps in the screening process. Conducting several plan-do-study-act cycles refined identification of patients appropriate to receive the measure. Over the three-year study, electronic health record notification tools and data collection were increasingly utilized to capture patients' information during their visit. RESULTS: Over 350 unique patients were screened during the assessment period. Electronic means replaced paper measures as time progressed. The percentage of patients completing the measure increased from 0% to 51.9% after the initial implementation of process improvement, advancing to 91.6% after the introduction of electronic measures. This average completion rate was sustained for 15 months. CONCLUSIONS: Using QI methodology helped identify the pragmatics of implementing a QoL assessment to enhance screening practices in a busy medical clinic. Assessment review at the time of appointment helped inform treatment and referral decisions.

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.

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.

Association between body mass index and tic disorders in school-age children.

OBJECTIVE: To explore the relationship between body mass index (BMI ) and the severity of tic disorders (TDs) in children 6-14 years old. METHODS: A total of 86 children diagnosed with TDs in a hospital between Jan. 2023 and Sept. 2023 were collected by convenient sampling method, and the general data and TD-specific data were collected and analyzed. RESULTS: Univariate analysis showed that patients with different Yale Global Tic Severity Scale (YGTSS) grades had statistically significant differences in age, BMI, residence, snacking pattern, weekly physical exercise frequency, weekly physical exercise time, and proportion of cesarean birth. Multiple linear regression analysis showed that the YGTSS score grades were related to BMI, snacking pattern, and cesarean birth of the patients. Correlation analysis revealed a positive correlation between BMI grades and the YGTSS score grades, with a higher BMI indicating more severe TDs. Predictive value evaluation showed that BMI, snacking pattern, and cesarean birth had predictive values for TD severity, and the highest value was found in the combined prediction. CONCLUSION: BMI, snacking pattern, and cesarean birth are of predictive values for the severity of TDs. In addition, BMI is positively correlated with the severity of TDs, and a higher BMI suggests more severe TDs.

A Test of the Behavioral Model of Tic Disorders Using a Dynamical Systems Framework.

Tic disorders are a class of neurodevelopmental disorders characterized by involuntary motor and/or vocal tics. It has been hypothesized that tics function to reduce aversive premonitory urges (i.e., negative reinforcement) and that suppression-based behavioral interventions such as habit reversal training (HRT) and exposure and response prevention (ERP) disrupt this process and facilitate urge reduction through habituation. However, previous findings regarding the negative reinforcement hypothesis and the effect of suppression on the urge-tic relationship have been inconsistent. The present study applied a dynamical systems framework and within-subject time-series autoregressive models to examine the temporal dynamics of urges and tics and assess whether their relationship changes over time. Eleven adults with tic disorders provided continuous urge ratings during separate conditions in which they were instructed to tic freely or to suppress tics. During the free-to-tic conditions, there was considerable heterogeneity across participants in whether and how the urge-tic relationship followed a pattern consistent with the automatic negative reinforcement hypothesis. Further, little evidence for within-session habituation was seen; tic suppression did not result in a reduction in premonitory urges for most participants. Analysis of broader urge change metrics did show significant disruption to the urge pattern during suppression, which has implications for the current biobehavioral model of tics.

Increase in Functional Tic Presentations in Sexual Orientation and Gender Identity Minority Youth During Coronavirus Disease 2019.

BACKGROUND: Functional tic disorders are among the least common functional movement disorders, but their prevalence rose during the coronavirus disease 2019 (COVID-19) pandemic. Although female adolescents develop functional neurological disorders at higher rates than males, investigations into sexual orientation and gender identity (SOGI) status of these patients are limited. METHODS: We completed a retrospective, cross-sectional time series examining the incidence of new-onset functional tic disorders in youth presenting to the Massachusetts General Hospital Movement Disorder clinics before and during the COVID-19 pandemic. Data were collected by searching for relevant International Classification of Diseases (ICD)-10 diagnostic codes in youth aged nine to 26 years using a hospital-wide data repository. Individual cases were reviewed for inclusion based on clinical criteria and expert consensus. RESULTS: The prevalence of functional tic presentations in youth rose 8.6-fold from pre- to postpandemic levels (Fisher exact test P < 0.001), whereas the prevalence of developmental tic presentations pre- and postpandemic remained stable (114 vs 112). SOGI minority youth comprised 37% of those with functional tics (total n = 19). Ninety five percent of patients with functional tics identified as female, with 10% of these identifying as transgender. CONCLUSIONS: Our data confirm previously demonstrated dramatic rises in functional tic presentations during the COVID-19 pandemic and, more notably, reveal a strong association with SOGI minority status. We highlight the potential link between functional tic disorders and SOGI minority status. Providing a safe and supportive clinical environment and addressing stress linked to SOGI minority status may help to improve patient prognosis.

Premonitory Urge in Patients with Tics and Functional Tic-like Behaviors.

BACKGROUND: Premonitory urges (PU) are well described in primary tics, but their frequency and intensity in functional tic-like behaviors (FTLB) are unclear. OBJECTIVE: To study the experience of PU in patients with FTLB. METHODS: We compared the results of the premonitory urge for tics scale (PUTS) in adults with tics and FTLB in the University of Calgary Adult Tic Registry. RESULTS: We included 83 patients with tics and 40 with FTLB. When comparing patients with tics, FTLB with tics and FTLB only, we did not detect significant differences either in the total PUTS score (P = 0.39), or in any of the individual PUTS item sub-scores (P values ranging between 0.11 and 0.99). CONCLUSIONS: Patients with FTLB report PU at similar frequency and intensity to patients with tics. This finding confirms that PU are not a useful feature to discriminate FTLB from tics.

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.

Evaluation of a psychoeducation group for children presenting with functional tic-like behaviours.

We describe the implementation and evaluation of an online psychoeducation group for young people experiencing functional tic-like behaviours (FTLBs) - a type of functional neurological disorder (FND). Across six groups, 50 participants completed pre- and post-group goal-based outcomes (GBOs) and 36 participants completed service-user feedback, which gathered qualitative and quantitative data about participants experiences of the group. Young people and their parents reported significant improvement in their GBOs following the group and increased knowledge and confidence in managing FTLBs. The findings highlight that virtual psychoeducation group intervention is an acceptable and effective first step in treatment of young people with FTLBs. We discuss implications for future intervention development.

We describe an online psychoeducation group for young people experiencing functional tic-like behaviours (FTLBs) ­ a type of functional neurological disorder (FND). Across six groups, 50 participants completed goal-based outcomes (GBOs) before and after the intervention. A total of 36 participants completed service-user feedback, which gathered data about participants experiences of the group. Young people and their parents reported significant improvement in their GBOs following the group and increased knowledge and confidence in managing FTLBs. The findings highlight that virtual psychoeducation group intervention is an acceptable and effective first step in treatment of young people with FTLBs. We discuss implications for future intervention development.

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.

Common pitfalls, and how to avoid them, in child and adolescent psychopharmacology: Part I.

As Faculty of the British Association for Psychopharmacology course on child and adolescent psychopharmacology, we present here what we deem are the most common pitfalls, and how to avoid them, in child and adolescent psychopharmacology. In this paper, we specifically addressed common pitfalls in the pharmacological treatment of attention-deficit/hyperactivity disorder, anxiety, bipolar disorder, depression, obsessive-compulsive disorder and related disorders, and tic disorder. Pitfalls in the treatment of other disorders are addressed in a separate paper (part II).

Tics emergencies and malignant tourette syndrome: Assessment and management.

Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by the presence of tics, frequently accompanied by a variety of neuropsychiatric comorbidities. A subset of patients with TS present with severe and disabling symptoms, requiring prompt therapeutic intervention. Some of these manifestations may result in medical emergencies when severe motor or phonic tics lead to damage of anatomical structures closely related to the tic. Examples include myelopathy or radiculopathy following severe neck ("whiplash") jerks or a variety of self-inflicted injuries. In addition to self-aggression or, less commonly, allo-aggression, some patients exhibit highly inappropriate behavior, suicidal tendencies, and rage attacks which increase the burden of the disease and are important components of "malignant TS". This subset of TS is frequently associated with comorbid obsessive-compulsive disorder. Therapeutic measures include intensive behavioral therapy, optimization of oral pharmacotherapy, botulinum toxin injections, and deep brain stimulation.