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).

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.

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.

Pediatric massage therapy for treatment of tic disorders in children: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tic disorder is a common neurodevelopmental disorder in childhood, characterized primarily by motor or vocal tics. However, there is no systematic evaluation of pediatric massage therapy for children with Tic disorder. This study aims to evaluate the effectiveness and safety of massage therapy for children with tic disorder through a comprehensive meta-analysis and systematic review. METHODS: We systematically searched relevant randomized controlled trials from various databases such as CBM, CNKI, VIP, Wanfang database, PubMed, Embase, Web of Science, Cochrane Library, and SINOMED, published up to October 2023. To collect randomized controlled trials on pediatric massage therapy or in combination with other therapies for the treatment of tic disorders in children. The risk of bias in the included articles was assessed using the Cochrane guideline. Meta-analyses were performed using Review Manager 5.4, and publication bias was evaluated by using Begg test and Egger test in Stata SE software. RESULTS: This meta-analysis included 19 randomized controlled trials with 1423 patients. Pediatric massage therapy alone or in combination with conventional medication demonstrated a significant increase in clinical effectiveness rates [risk ratios = 1.15, 95% confidence interval [CI] (1.10, 1.20), Z = 6.54, P < .001], and reduced Yale Global Tie Severity Scale scores [standardized mean difference = -0.85, 95% CI (-1.50, -0.19), Z = 2.54, P = .01] and traditional Chinese medicine syndrome scores [standardized mean difference = -1.35, 95%CI (-2.08, -0.63), Z = 3.66, P = .0002]. In terms of adverse reactions, there was no statistical difference between the experimental and control groups [risk ratios = 0.26, 95% CI (0.14, 0.49), Z = 4.25, P < .001]. The Begg test and Egger test results indicated no publication bias. CONCLUSION: Evidence suggests that pediatric massage therapy is effective in improving tic disorders in children.

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.

Associations between ADHD and risk of six psychiatric disorders: a Mendelian randomization study.

BACKGROUND: Observational studies and diagnostic criteria have indicated that Attention Deficit Hyperactivity Disorder (ADHD) frequently comorbid with various psychiatric disorders. Therefore, we conducted a Mendelian randomization (MR) study to explore this potential genetic association between ADHD and six psychiatric disorders. METHODS: Using a two-sample Mendelian randomization (MR) design, this study systematically screened genetic instrumental variables (IVs) based on the genome-wide association studies (GWAS) of ADHD and six psychiatric disorders, with the inverse variance weighted (IVW) method as the primary approach. RESULTS: The study revealed a positive and causal association between ADHD and the risk of ASD, with an odds ratio (OR) of 2.328 (95%CI: 1.241-4.368) in the IVW MR analysis. Additionally, ADHD showed a positive causal effect on an increased risk of schizophrenia, with an OR of 1.867 (95%CI: 1.260-2.767) in the IVW MR analysis. However, no causal effect of Tic disorder, Mental retardation, Mood disorders and Anxiety disorder with ADHD was found in the analysis mentioned above. CONCLUSION: Our MR analysis provides robust evidence of the causal role of ADHD in increasing the risk of ASD and schizophrenia. However, ADHD is not associated with the risk of Tic Disorder, Mental Retardation, Mood Disorders and Anxiety Disorder. This suggests the need for increased attention to the co-occurrence of ADHD-ASD or ADHD-schizophrenia and the implementation of timely intervention and treatment.

In Memoriam: Professor Joseph Biederman's Contributions to Child and Adolescent Psychiatry.

OBJECTIVE: To provide an overview of Joe Biederman's contributions to child and adolescent psychiatry. METHOD: Nine colleagues described his contributions to: psychopharmacology, comorbidity and genetics, pediatric bipolar disorder, autism spectrum disorders, Tourette's and tic disorders, clinical and neuro biomarkers for pediatric mood disorders, executive functioning, and adult ADHD. RESULTS: Joe Biederman left us with many concrete indicators of his contributions to child and adolescent psychiatry. He set up the world's first pediatric psychopharmacology clinic and clinical research program in child adolescent psychiatry. As a young faculty member he began a research program that led to many awards and eventual promotion to full professor at Harvard Medical School. He was for many years the most highly cited researcher in ADHD. He achieved this while maintaining a full clinical load and was widely respected for his clinical acumen. CONCLUSION: The world is a better place because Joe Biederman was here.

Treating Tourette Together: An Agenda for Patient-Centered Research Focused on Comprehensive Behavioral Intervention for Tics.

To establish a patient-centered agenda for research that will lead to effective, widespread availability, adoption, and utilization of evidence-based behavioral treatment of Tourette syndrome and other tic disorders (TDs), we planned and executed a multistage, collaborative "Treating Tourette Together" research planning project with researchers, clinicians, patients, families, and other interested parties. Priorities for future behavioral treatment research were solicited from these parties via anonymous community surveys, a 2-day research planning summit with 46 individuals representing key stakeholder groups, and community response to summit reports. Four high-priority research domains were identified: (a) expanding treatment access, (b) improving treatment outcomes, (c) optimizing treatment within a broader care model, and (d) evaluating outcomes beyond tic severity. Community-engaged participatory research models can efficiently delineate clear and actionable priorities for clinical research. This approach holds promise for improving the impact of clinical research in TDs and other neuropsychiatric disorders.

Tic disorder in allergic rhinitis children and adolescents: a case-control study.

BACKGROUND: Allergic rhinitis is the most common allergic disease. It can accompany psychological disorders such as tic disorders due to the prolonged course of the symptoms of allergic rhinitis. This pioneer case-control study aims to investigate tic disorders in children and adolescents under 18 years of age diagnosed with allergic rhinitis. METHOD: The case group in this study consisted of patients who had both allergic rhinitis and tic disorders. Patients with allergic rhinitis without tic disorders were also enrolled as the control group with matched gender and age. Demographic characteristics, tic classifications, and contributing factors for allergic rhinitis and tic disorders were studied among the cases. Tic disorders were evaluated using DSM-5 criteria for the classification of tic disorders. RESULTS: 47 patients in the case group and 47 patients in the control group were included in this study. 53.2% and 46.8% were males and females in the case group, respectively. The mean age of the patients was 10.46 ± 3.97 years old. Sound tics were more common among the patients compared to motor tics. Patients with concomitant AR and tic disorders had more days per week with AR symptoms (P-value ≤ 0.001; OR (every day vs. three days a week = 11.02(2.98, 40.76))). Most patients with sound tick were women (p: 0.026), and most patients with motion tic were in the Provisional tic disorder group (p: 0.001). The history of infantile eczema was seen more in patients without sound tic (p: 0.025), and otitis media was significantly less common among patients with sound tics (p: 0.026). Provisional tic disorder was the most common class among the patients. In the case group (coexistence between allergic rhinitis and tic) compared to the control group, patients had significantly more days with AR symptoms per week. CONCLUSION: This preliminary study indicates that Provisional tic disorder was the most common classification of tic among patients with allergic rhinitis, especially in patients with motor tics. Asthma in motor tics, a history of food allergy in infancy, and a history of infantile eczema were also common among patients with vocal tics. Also, patients with allergic rhinitis and tic had more severe disease (more symptoms per week) than those with rhinitis alone. These findings emphasize the association of tic disorders with immunological pathways.

Efficacy of differential reinforcement of other behaviors therapy for tic disorder: a meta-analysis.

INTRODUCTION: Recently, studies on behavioral tic suppression techniques have gained popularity as opposed to pharmacological alternatives that often have potentially dangerous side effects. Differential Reinforcement of Other Behaviors therapy (DRO) is one such behavioral technique whose efficacy in tic suppression has been experimentally demonstrated albeit in studies with very few patients, and lacking statistical power. Here, we conducted a meta-analysis of these studies to improve their overall power and explore whether DRO intervention is really effective for tic suppression. MATERIALS AND METHODS: PubMed, Embase, PsycINFO, and Cochrane Library were searched from inception to August 30, 2023. Only original interventional studies that examined the efficacy of DRO for tic suppression were included. RESULTS: A total of 8 no control interventional studies involving 79 children with tic disorders were recruited. Most of the children had moderate tic severity. The pooled mean Yale Global Tic Severity Scale (YGTSS) score was 24.64 (95% CI: 21.99 - 30.12, p = < 0.00001, I2 = 87%). In terms of efficacy of the DRO technique for tic suppression, the results showed that DRO was effective in reducing tic frequency among the children. The pooled standardized mean difference (SMD) was -10.25 (95% CI: -14.71 - -5.79, p = < 0.00001) with I2 = 94%. CONCLUSION: In conclusion, this study revealed that DRO is potentially an effective tic suppression technique for temporarily managing tic disorder. It also showed that DRO could be employed for both moderate and severe tic disorders. However, the technique bears crucial limitations that limit its implementation outside of experimental settings. More studies are needed to address these limitations and improve its applicability in the real world.

An investigation into mothers' experiences of their children's functional tic-like behaviour and tic attacks.

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.

Placebo and Nocebo Responses in Pharmacological Trials of Tic Disorders: A Meta-Analysis.

BACKGROUND: Clinical trials of new drugs for tic disorders (TD) often fail to yield positive results. Placebo and nocebo responses play a vital role in interpreting the outcomes of randomized controlled trials (RCTs), yet these responses in RCTs of TD remain unexplored. OBJECTIVE: The aim was to assess the magnitude of placebo and nocebo responses in RCTs of pharmacological interventions for TD and identify influencing factors. METHODS: A systematic search of the Embase, Medline, Cochrane Central Register of Controlled Trials, and PsycINFO databases was conducted. Eligible studies were RCTs that compared active pharmacological agents with placebos. Placebo response was defined as the change from baseline in TD symptom severity in the placebo group, and nocebo response as the proportion experiencing adverse events (AEs) in this group. Subgroup analysis and meta-regression were performed to explore modifying factors. RESULTS: Twenty-four trials involving 2222 participants were included in this study. A substantial placebo response in TD symptom severity was identified, with a pooled effect size of -0.79 (95% confidence interval [CI] -0.99 to -0.59; I2 = 67%). Forty-four percent (95% CI 27% to 63%; I2 = 92%) of patients experienced AEs while taking inert pills. Sample size, study design, and randomization ratio were correlated with changes in placebo and nocebo responses. CONCLUSION: There were considerable placebo and nocebo responses in TD clinical trials. These results are of great relevance for the design of future trials and for clinical practice in TD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration ID CRD42023388397. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

What are the Key Phenomenological Clues to Diagnose Functional Tic-Like Behaviors in the Pandemic Era?

BACKGROUND: Functional tic-like behaviors (FTLBs) can be difficult to distinguish from tics. OBJECTIVES: To describe the phenomenology of FTLBs in youth and assess the movements and vocalizations most suggestive of the diagnosis. METHODS: We compared the phenomenology of tics between youth (<20 yr) with FTLBs and with primary tics from our Registry in Calgary, Canada. RESULTS: Two hundred and thirty-six youths were included: 195 with primary tics (75% males; mean age: 10.8 yr) and 41 with FTLBs (98% females; 16.1 yr). In the bivariate models, FTLBs were most associated with copropraxia (OR = 15.5), saying words (OR = 14.5), coprolalia (OR = 13.1), popping (OR = 11.0), whistling (OR = 9.8), simple head movements (OR = 8.6), and self-injurious behaviors (OR = 6.9). In the multivariable model, FTLBs were still associated with saying words (OR = 13.5) and simple head movements (OR = 6.3). Only 12.2% of youth with FTLBs had throat clearing tics (OR = 0.2). CONCLUSIONS: This study shall help physicians diagnose youth with FTLBs according to the presence/association of specific movements and vocalizations.

Advancements in the phenomenology, assessment, and treatment of Tourette syndrome.

PURPOSE OF REVIEW: Tourette syndrome (TS) and chronic tic disorders, collectively referred to as TS, are relatively common childhood onset neuropsychiatric conditions associated with functional impairment and distress. Over the past several years, clinical research has contributed to the advancement of the field's understanding of mechanisms and clinical correlates of TS. This progress has led to the development of key assessment tools and the implementation of novel interventions for individuals with TS. RECENT FINDINGS: This article provides a review of innovative TS research focusing on four key themes: investigation of clinical phenomenology of TS; validation of assessment tools for TS; dissemination of current evidence-based treatments for TS; and exploration of new intervention programs. SUMMARY: Cumulatively, this growing body of work presents considerable progress and provides a path forward to improve the assessment and treatment of TS.

Impact of movie and video game elements on tic manifestation in children.

BACKGROUND AND PURPOSE: Children in developed countries spend a significant portion of their waking hours engaging with audiovisual content and video games. The impact of media consumption on children's health and well-being has been widely studied, including its effects on tic disorders. Previous studies have shown that tic frequency can both increase and decrease during activities like gaming and television watching, resulting in mixed findings. METHODS: To better understand the impact of audiovisual media on tics, we conducted a fine-grained tic manifestation analysis. We focused on the effects of the impact of a movie scene with suspensful elements and a video game designed to heighten anticipation, thought to stimulate phasic and striatal dopamine release. We closely monitored tic frequency throuhghout these experiences based on moment-to-moment tic annotation. The study included 20 participants (19 males aged 7-16) diagnosed with tic disorders (Yale Global Tic Severity Scale≥8), and we tested the replicability of our findings with an independent group of 36 children (15 females, aged 7-15) with tic disorders. RESULTS: During film viewing, we observed significant synchronization in the temporal tic patterns of various individuals despite diversity in their tic profiles. Furthermore, employing a video game developed for our study, we found that tic frequency increases during anticipation of a pending reward. This finding was replicated in a second experiment with an independent cohort. CONCLUSIONS: Our results indicate that tic frequency is affected by media elements in the short-term, and call for further investigation of the long-term impacts of exposure to such tic triggers.

Pharmacological treatment of Tourette's syndrome: from the past to the future.

Tourette's syndrome (TS) is a neuropsychiatric disease featuring tics and vocal tics, with a prevalence of approximately 1%, including 75% of the total number of male patients. TS seriously disturbs the patients' career, education, and life and brings a serious and unbearable psychological burden to the patients themselves and their families. At present, there are no specific clinical medications recommended for treating TS. Therefore, it is necessary to select the appropriate medication for symptomatic treatment based on the doctor's personal experience and the patient's symptoms, with the main goal of relieving symptoms, thus improving the patient's social skills and psychological problems. Here we conducted a comprehensive search on PubMed to review and organize the history and current status of the development of drug therapy for TS through a timeline format. We also systematically evaluated the effects of each drug for TS treatment to summarize the current problems and new research directions and to provide some ideas for clinical treatment.

Prevalence and influencing factors of sleep problems in tic disorders: a meta-analysis.

BACKGROUND: Sleep problems are commonly observed in patients with tic disorders. Nevertheless, studies have demonstrated a wide variation in the prevalence of sleep disturbances among this population. Consequently, it remains ambiguous whether sleep issues are inherently characteristic of tic disorders or are influenced by external factors. METHODS: We conducted a comprehensive search across various databases and performed a meta-analysis to determine the prevalence of sleep problems in tic disorders. Additionally, we assessed pre-existing comorbidities and associated characteristics using meta-regression analysis. RESULTS: After including 33 studies in the final meta-analysis, we found that the pooled prevalence of sleep problems in tic disorders was 34% (95%CI: 26% to 43%). Meta-regression analysis revealed that the presence of co-occurring symptoms of ADHD (p < 0.05), obsession compulsive disorder/behaviours (p < 0.05), anxiety (p < 0.001), and mood disorders (p < 0.001) was associated with an increased likelihood of experiencing sleep problems. CONCLUSIONS: Our findings consistently indicate that individuals with tic disorders frequently encounter significant sleep problems. This underscores the importance of routinely screening for sleep problems during clinical assessments. Effectively managing sleep problems in patients with tic disorders is crucial not only for the well-being of the patients themselves but also for their families.