Treatment Of Tourette Syndrome Research Articles

Network Pharmacology Combined with Animal Models to Investigate the Mechanism of ChangPu YuJin Tang in the Treatment of Tourette Syndrome.

ChangPu YuJin Tang (CPYJT) is a Chinese herbal formula that has been shown to be an effective therapeutic strategy for pediatric patients with Tourette Syndrome (TS). Using an integrated strategy of network pharmacology and animal model, the aim of this study was to investigate the mechanism of CPYJT in the treatment of TS. Compound libraries of CPYJT were established using databases, such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The TCMSP database and Swiss Target Prediction database were used to predict the targets. The above results were constructed into a CPYJT-Drug-Component-Target network. Moreover, TS targets were predicted using GeneCards and other databases. The targets corresponding to the potential ingredients in CPYJT and the targets corresponding to TS were taken as the intersections to construct the CPYJT-TS network. The target network was analysed by PPI using the string database. GO and KEGG enrichment analyses were performed on the target network. The whole process was performed using Cytoscape 3.7.2 to make visual network diagrams of the results. CPYJT was characterised by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS). Transmission Electron Microscopy (TEM) was used to observe the structural changes of CPYJT on the neuronal cells of the IDPN model rats. RT-PCR and Western Blot were used to analyse the changes in the mRNA and protein expression levels of BDNF, TrkB, PI3K, and AKT in the cortex, striatum, and thalamus brain regions after CPYJT administration in IDPN model rats. Network pharmacology and UHPLC-MS studies revealed that CPYJT acted on the TS through multiple neurotransmitters and the BDNF/TrkB and PI3K/AKT signalling pathways. CPYJT ameliorated neurocellular structural damage in the cortex, striatum, and thalamus of TS model rats. Additionally, CPYJT up-regulated the levels of BDNF, TrkB, PI3k, and AKT in the cortex, striatum, and thalamus of TS model rats. It was found that CPYJT protected neuronal cells from structural damage in multiple brain regions and affected the expression levels of BDNF, TrkB, PI3K, and Akt in the cortex, striatum, and thalamus during TS treatment.

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.

GBA-related diseases and the application in Tourette syndrome treatment

This paper discusses the gut-brain axis (GBA) and how it takes part in various neurological diseases, including Alzheimers disease (AD), Attention-deficit hyperactivity disorder (ADHD), and Tourette syndrome. The gut microbiota, inducing vital communications with the brain through the GBA, is not to be neglected in maintaining physiological balance, with the potential to become a source of new therapeutic opportunities for treating these diseases. Current studies show that methods such as personalized diets, oral bacteriotherapy, and multi-strain probiotics like SLAB51 and DEX have promising results in treating AD and ADHD through manipulation of the biotas. Based on the analysis of previous research, this paper finds how changes in gut microbiota amount in feces between healthy and TS mice, in particular the decrease in Firmicutes and Actinobacteria, and the increase in Bacteroidetes and Proteobacteria. However, future studies and experiments are required to evaluate potential side effects of microbiome alterations in humans, and potential treatments for Tourettes syndrome based on gut microbiota analysis. The GBA is a promising area for developing new therapeutic approaches for neurological diseases, and future research in this field holds great potential for advancements in the treatment of these disorders currently with no verified cures.

Automated Quantification of Eye Tics Using Computer Vision and Deep Learning Techniques.

Tourette syndrome (TS) tics are typically quantified using "paper and pencil" rating scales that are susceptible to factors that adversely impact validity. Video-based methods to more objectively quantify tics have been developed but are challenged by reliance on human raters and procedures that are resource intensive. Computer vision approaches that automate detection of atypical movements may be useful to apply to tic quantification. The current proof-of-concept study applied a computer vision approach to train a supervised deep learning algorithm to detect eye tics in video, the most common tic type in patients with TS. Videos (N = 54) of 11 adolescent patients with TS were rigorously coded by trained human raters to identify 1.5-second clips depicting "eye tic events" (N = 1775) and "non-tic events" (N = 3680). Clips were encoded into three-dimensional facial landmarks. Supervised deep learning was applied to processed data using random split and disjoint split regimens to simulate model validity under different conditions. Area under receiver operating characteristic curve was 0.89 for the random split regimen, indicating high accuracy in the algorithm's ability to properly classify eye tic vs. non-eye tic movements. Area under receiver operating characteristic curve was 0.74 for the disjoint split regimen, suggesting that algorithm generalizability is more limited when trained on a small patient sample. The algorithm was successful in detecting eye tics in unseen validation sets. Automated tic detection from video is a promising approach for tic quantification that may have future utility in TS screening, diagnostics, and treatment outcome measurement. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Working Mechanisms of Exposure and Response Prevention in the Treatment of Tourette Syndrome and Tic Disorders Revisited: No Evidence for within-Session Habituation to Premonitory Urges.

Exposure and response prevention (ERP) has been shown to be an effective treatment for Tourette syndrome (TS) and chronic tic disorders (CTD). ERP is based on voluntary tic suppression in combination with prolonged exposure to premonitory urges preceding tics. A prevailing hypothesis of the working mechanism underlying ERP in tics is habituation to the premonitory urges as a result of prolonged exposure. However, results so far are equivocal. This study aims to further explore the relation between urges and ERP in tics, by investigating the course of premonitory urges during ERP sessions. Using a data-driven approach, within-session habituation to premonitory urge intensity was investigated. In total, 29 TS patients rated urge intensity at seven timepoints during ten 1 h ERP sessions. Latent growth modeling showed an increase in urge intensity during the first 15 min of each session followed by a plateau in the remaining 45 min of the session. This does not support the idea of within-session habituation to premonitory urges as a working mechanism of ERP. Other potential underlying working mechanisms are discussed and should be tested in future research.

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.

Psychosocial stress in children with Tourette syndrome and chronic tic disorder

BackgroundThis study aimed to understand the longitudinal relationship between psychosocial stress with tic exacerbation in children with Tourette syndrome (TS) and chronic tic disorder. MethodsConsecutive ratings of tic severity as well as child and parental reports of psychosocial stress were obtained for 373 children (296 males, 77 females; mean age 9y 5mo; SD 3y 3mo) with TS and chronic tic disorder between January 2018 and December 2020. The Yale Global Tic Severity Scale (YGTSS) global severity score, total tic score, and impairment rating were calculated. The stressful events and YGTSS measurements were used and treated as time-varying variables in the analyses. Models that controlled for non-independence among the repeated observations using a random intercept and random slope model were employed. Each participant was treated as a random factor in the modelling. ResultsFamily-related stress, personal relationship stress and school-related stress were independently associated with increasing YGTSS global severity, total tic score, and impairment rating over time. An increased number of stressful events were associated with increased severity of tics. ConclusionFamily, personal relationships, and school-related stress were consistently associated with the exacerbation of tics. Managing these stressful events is important in the treatment of TS and chronic tic disorder.

Efficacy and Safety of Acupuncture Combined with Herbal Medicine for Children and Adolescents with Tourette Syndrome: A Systematic Review and Meta-Analysis

Background: With the increasing prevalence of Tourette syndrome (TS), the search for alternative therapy for TS is a growing public concern. In recent years, a growing number of randomized controlled trials (RCTs) have revealed the value of acupuncture combined with herbal medicine for the treatment of TS; however, its holistic efficacy and safety remains unclear. This study aimed to evaluate the efficacy and safety of acupuncture combined with herbal medicine and to provide preliminary evidence for clinical practice. Methods: Eight databases were searched from their establishment to November 27, 2022, to collect RCTs of acupuncture combined with herbal medicine for TS treatment. Two researchers independently completed the study screening, data extraction, and risk of bias assessment by using NoteExpress, Excel, and Cochrane Risk of Bias Tool 2.0 (RoB 2.0). Stata 15.0 software was applied to conduct meta-analysis. Results: A total of 1,400 participants in 18 RCTs were included. Compared with the Western medicine, acupuncture combined with herbal medicine had better curative effect in the field of effective rate (risk ratio [RR] = 1.18, 95% CI: [1.12, 1.23], p < 0.05, I² = 0%), Yale Global Tic Severity Scale (YGTSS) total score (mean difference [MD] = −3.91, 95% CI: [−5.49, −2.33], p < 0.05, I² = 96.4%), TCM syndrome total score (MD = −2.42, 95% CI: [−3.71, −1.13], p < 0.05, I² = 87.1%), and serum IgE negative rate (RR = 3.41, 95% CI: [1.69, 6.87], p < 0.05, I² = 0%). Furthermore, acupuncture combined with herbal medicine reduced the adverse reaction rate (RR = 0.20, 95% CI: [0.14, 0.30], p < 0.05, I² = 0%) and the recurrence rate (RR = 0.27, 95% CI: [0.13, 0.52], p < 0.05, I² = 0%). Conclusion: This study demonstrated the efficacy and safety of acupuncture combined with herbal medicine, which is probably a better alternative therapy for TS. However, the small number, low quality, and potential bias of the included studies caused the limitations of our results. More high-quality RCTs are required to provide supplementary evidence in the future.

Present situation on the causes and treatments of tourette syndrome

Tourette Syndrome (TS), a neurological disorder classified as the most complex form of tic disorder in the DSM-5, has remained a prominent concern for the adolescent population. Owing to its complexity and the unknowability of its physiology, it currently has no cure. Through the review of two family studies, two twin studies, one Genome-Wide Association Study, and two other reviews, firm evidence for additive genetic influences and non-shared environmental influences was found, suggesting TSs high heritability. Specific genetic factor (SNP-rs2504235), environmental (pre-and peri-natal) factors, and the interaction between these factors were evident from the studies as well. Through the analysis of these findings, one coping strategy was emphasized over the two existing classes, pharmacological and non-pharmacological, of typical treatments: preventative approaches under the assistance of advanced technology like genetic testing. The inability of the now available treatments to cure TS and their respective side effects cause them to be less desirable than prevention as early actions were shown to be effective in hindering the disorders deterioration and persistence.

Integrated UPLC-MS, network pharmacology, and intestinal flora analysis to determine the treatment effect of Qiangzhi decoction on comorbid Tourette syndrome and RRTI.

Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics. Recurrent respiratory tract infection (RRTI), a commonly occurring disease in childhood, correlates with recurrent and severe course of tic symptoms. Qiangzhi decoction (QZD) is a traditional Chinese medicine that can alleviate TS symptoms while reducing the recurrence of RRTI. However, the mechanism of QZD on TS and RRTI remains unclear. This study aimed to determine the treatment effect of QZD on comorbid TS and RRTI by integrating ultrahigh-performance liquid chromatography mass spectrometry (UPLC-MS), network pharmacology, and intestinal flora analysis. The components of QZD were first identified by UPLC-quadrupole (Q)-orbitrap-MS/MS. The mechanism of QZD on comorbid RRTI and TS was investigated by a series of network pharmacological methods, including target prediction and bioinformatics analysis. Finally, a comorbid TS and RRTI rat model was established by intraperitoneal injection of 3,3-iminodipropionitrile (IDPN), cyclophosphamide (CTX), and lipopolysaccharide (LPS). Alteration of gut microbiota in the alleviation of TS and RRTI by QZD was investigated via intestinal flora analysis. The results of UPLC-Q-orbitrap-MS/MS showed that QZD had 96 types of chemical components. The network pharmacology results demonstrated that targets of QZD involved in the treatment of TS and RRTI involved 1045 biological processes (BPs), 109 cellular components (CCs), and 133 molecular functions (MFs), including synaptic and transsynaptic signaling, chemical synaptic transmission, neurotransmitter receptor activity, G protein-coupled amine receptor activity, and serotonin receptor activity, among others. Firmicutes, Bacteroidetes, Coprococcus, and Lachnospiraceae played crucial roles in gut microbiota of a QZD-treated comorbid TS and RRTI model. Our results revealed QZD provided a multicomponent, multitarget, and multipathway synergistic treatment of comorbid TS and RRTI.

Median Nerve Stimulation for Treatment of Tics: A 4-Week Open Trial with Ecological Momentary Assessment.

Median nerve stimulation (MNS) at 10-12 Hz was recently proposed as a treatment for Tourette syndrome and other chronic tic disorders (TS/CTD). We report on 31 participants ages 15-64 with TS/CTD in an open-label, comparative (within-group, several time points) study of MNS (ClinicalTrials.gov registration number NCT05016765). Participants were recruited from completers of a randomized controlled trial (RCT) of MNS and were given a transcutaneous electrical nerve stimulation (TENS) unit to use as desired for 12 Hz MNS for 4 weeks. Participants were instructed to complete surveys regarding tic symptoms and stimulation discomfort before and after stimulation, as well as twice daily when randomly prompted by text message. Participants also completed an extensive final survey. Twenty-seven participants completed the study. Median device use was 1.5 days per week and 50 min per day used. Tic frequency improved during MNS (mean improvement: 1.0 on a 0-5 scale, p < 0.001), as did tic intensity (mean improvement: 0.9, p < 0.001). Mean discomfort was mild (1.2 on a 3-point scale). In total, 21 participants (78%) planned to continue using the device. Participants' results in this study did not correlate significantly with their results in the blinded RCT. We found MNS to improve tic frequency and intensity with minimal side effects.

Protocol of a randomized controlled trial to investigate the efficacy and neural correlates of mindfulness-based habit reversal training in children with Tourette syndrome.

Tourette syndrome (TS) is a developmental neuropsychiatric disorder. Behavior therapy, especially habit reversal training (HRT), has gradually become regarded as one of the core therapies for TS. Mindfulness approaches can improve psychological adjustment and reduce stress and anxiety, suggesting potential benefits when incorporated into behavior therapy. To improve the efficacy of HRT, we combined it with mindfulness, an approach named mindfulness-based habitual reversal training (MHRT). The aim of this protocol is to investigate the efficacy and neural mechanisms of MHRT for TS. We will perform a randomized control trial (RCT) to evaluate the efficacy and neural mechanisms of MHRT. The sample will include 160 participants (including 120 patients with TS and 40 healthy controls). The patient sample will be randomly divided into three groups exposed to three different types of training: MHRT, HRT, and psychoeducation and supportive therapy (PST). Participants will be assessed and undergo resting-state fMRI scans at baseline and at the end of the 12-week training. The Yale Global Tic Severity Scale (YGTSS) and Premonitory Urge for Tic Scale (PUTS) will be used to assess the severity of tic symptoms and premonitory urges. The primary outcomes are change scores on the YGTSS and other assessments from baseline and the end of the training. The secondary outcomes are the neural correlates of these trainings among these groups based on graph theory, which is used to characterize brain functional connectivity networks. The default mode network (DMN) and the salience network (SN) will be assessed (which have been associated with mindfulness as well as the generation of tic symptoms) by network parameters, including clustering coefficients and shortest path lengths. Changes in these network parameters will be regarded as the neural correlates of the behavioral training. MHRT was newly developed for the treatment of TS. MHRT may lead to greater reductions in tic severity than traditional HRT. Changes in the network parameters of the DMN and SN may show associations with the efficacy of MHRT. http://www.chictr.org.cn, ChiCTR2100053077, China.

Trends of Tourette Syndrome in children from 2011 to 2021: A bibliometric analysis.

Analyze the research status of Tourette Syndrome (TS) in children by CiteSpace and determine the current research hotspots and frontiers. We chose publications indexed in the Web of Science Core Collection (WoSCC) database for studies related to TS in children from 2011 to 2021. We built online cooperation maps of countries/regions, institutions, authors, journals, references, and keywords by CiteSpace, and identified hotspots and frontiers of study for children's TS. A total of 1,232 publications about TS in children were downloaded from the WoSCC. The USA (414) was the country with the highest rate of production, and University College London (87) was the institution that had the highest publication rate. Andrea Eugenio Cavanna was the most prolific author (39 papers). There was inactive cooperation between institutions, countries/regions, and authors. The Journal of European Child & Adolescent Psychiatry was the most active journal. Hot topics focused on epidemiology, comorbidities, deep brain stimulation, behavioral therapy, basal ganglia, pharmacological treatment, and risk factors of TS in children. According to the CiteSpace results, this study found that authors, countries/regions, and institutions were not actively working together. Current research hotspots mainly consist of epidemiology, comorbidities, deep brain stimulation, behavior therapy, and basal ganglia. The main research trends include comorbidities, pharmacological treatment, and risk factors. Therefore, international cooperation should be strengthened in the future, and it should be mindful of the psychiatric comorbidities of TS, the choice of intervention measures, and early warning of risk factors.

Effects of service animals on Tourette syndrome: a case study

Patients with Tourette syndrome have difficulty maintaining a good quality of life because of motor or vocal tics. Therefore, a review of current and novel interventions is needed to help clinicians and patients when choosing the best interventions for the patient's specific situation. This case study looks at the effects of a service animal on the impairment level and quality of life of a patient with Tourette syndrome. In this case, evidence-based practice includes patient perspectives, clinical expertise and a literature search. The methods used in this case study include quantitative clinician rating scales, qualitative observation and patient reporting. The patient has reported fewer vocal tics when the service dog is within the patient's vicinity and the patient can cue her kinaesthetically. In this case, there are very clear benefits to using a service dog in the treatment of Tourette syndrome.

Jing-an oral liquid alleviates Tourette syndrome via the NMDAR/MAPK/CREB pathway in vivo and in vitro

Context Jing-an oral liquid (JA) is a Chinese herbal formula used in the treatment of Tourette syndrome (TS); however, its mechanism is unclear. Objective To investigate the effects of JA on amino acid neurotransmitters and microglia activation in vivo and in vitro. Materials and methods Sixty male Sprague–Dawley rats were divided into a control group and 5 TS groups. TS was induced in rats with intraperitoneal injection of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1 mg/kg) and in BV2 cells with lipopolysaccharide. Control and model rats were administered saline, whereas treatment groups were administered JA (5.18, 10.36, or 20.72 g/kg) or tiapride (a benzamide, 23.5 mg/kg) by gavage once daily for 21 days. Stereotypic behaviour was tested. The levels of N-methyl-d-aspartate receptor (NMDAR)/mitogen-activated protein kinase/cAMP response element-binding protein (CREB)-related proteins in striatum and BV2 cells were measured via western blots. CD11b and IBa1 levels were also measured. Ultra-high-performance liquid-chromatography was used to determine γ-aminobutyric acid (GABA), glutamic acid (Glu), and aspartic acid (ASP) levels. Results JA markedly alleviated the stereotype behaviour (25.92 ± 0.35 to 13.78 ± 0.47) in rats. It also increased NMDAR1 (0.48 ± 0.09 to 0.67 ± 0.08; 0.54 ± 0.07 to 1.19 ± 0.18) expression and down-regulated the expression of p-ERK, p-JNK, p-P38, and p-CREB in BV2 cells and rat striatum. Additionally, Glu, ASP, GABA, CD11b, and IBa1 levels were significantly decreased by JA. Discussion and conclusions JA suppressed microglia activation and regulated the levels of amino acid neurotransmitters, indicating that it could be a promising therapeutic agent for TS.

Mechanisms of Action of Semen Ziziphi spinosae in the Treatment of Tourette Syndrome.

BackgroundSemen Ziziphi spinosae, known as Suanzaoren (SZR) in Chinese, is a Chinese herbal medicine widely used in sedatives and tranquilizers. Although SZR is important for the clinical treatment of Tourette syndrome (TS), its mechanism of action remains unclear. Therefore, we investigated the pharmacological mechanisms of SZR in TS treatment using network pharmacology and systems biology approaches.MethodsThe bioactive components and potential targets of SZR were screened using the TCMSP database. UniProt was used to identify targets by mapping the known genes related to SZR. The known genes related to TS were identified by GeneCards and OMIM databases. A protein-protein interaction network was constructed using information from STRING 11.0 database. Cytoscape 3.8.0 software and Bioinformatics online platform were used for plotting this network. Gene ontology and KEGG enrichment analyses were performed using Metascape. Finally, AutoDock was used to verify the molecular docking.ResultsWe found that SZR had 10 active compounds. There were 30 overlapping target genes between TS and SZR. These genes were associated with several signaling and metabolic pathways. AChE, SLC6A4, and HTR3A were the top three hub genes. The active components in SZR had a high binding affinity for the key targets.ConclusionSZR therapy for TS could achieve network regulation through the action of various active components of Chinese medicine on different targets and generate a complex regulatory relationship via interaction with potential targets, thereby playing a therapeutic role. Thus, SZR is a potential candidate for treating TS because it regulates nervous system functions.

FV 1 Segregating the prefrontal cortex by means of deep brain stimulation

Introduction: Neurocircuits are involved in the motor, cognitive, and affective dysfunctions of multiple brain disorders. Functional segregation into these domains has been widely defined on a fronto- cortical basis. However, despite considerable interaction, these functional domains remain partitioned to some extent at (sub)thalamic levels (1). To map the functional organization of the the frontal cortex (FC), we employ optimal connectivity profiles from successful deep brain stimulation (DBS) electrodes to the same target, which receives input from the entire FC, in four different disorders. Specifically, we identify cortical projection sites that, on a group level, associate with maximal improvements following subthalamic nucleus (STN) DBS in dystonia (DYT), Parkinson's disease (PD), Tourette syndrome (TS) or obsessive-compulsive disorder (OCD). Patients and Methods: Using Lead-DBS (2), stimulation volumes were estimated for six patient cohorts from six centers, each implanted with DBS to the STN for treatment of either DYT (N = 62), PD (N = 51), TS (N = 14), or OCD (N = 19). Via DBS Network Mapping (3) we derived disease-specific structural connections between cortex and STN from a normative connectome (4) that relate to optimal clinical outcomes. Results: Functional organization in the STN and FC was reflected along a caudo-rostral gradient (Fig. 1). Beneficial DBS networks for DYT predominantly projected to the primary motor cortex, while in PD, electrode connectivity to pre- and supplementary motor areas, in TS to the dorsomedial preFC, and in OCD to ventromedial, dorsal anterior cingulate and dorsolateral preFC emerged. Conclusion: Our findings demonstrate the usefulness of DBS to investigate the organizational gradient of frontal network (dys)function. As such, they bear both interest for cognitive neurosciences as well as clinical-translational value for circuit-guided DBS.

Is Traditional Chinese Medicine Effective in Treating Tic Disorders (Tourette Syndrome)? A Meta-Analysis of Randomized Controlled Trials

Introduction: Traditional Chinese medicine (TCM) is a type of alternative medicine that has been widely utilized in the prevention and treatment of neuropsychiatric diseases such as schizophrenia, ADHD, Alzheimer disease, and Tourette syndrome (TS) in many countries. However, the results regarding TCM’s effectiveness and safety in treating TS are conflicting. Therefore, the goal of the present study is to analyze and summarize the available literature related to the efficacy of TCM in the treatment of tic disorders, especially TS. Methods: Relevant articles for the meta-analysis were searched using appropriate keywords from PubMed, MEDLINE, and CENTRAL databases. Event data for TCM for the treatment of TS in the control and intervention arms were determined from the randomized controlled trials, and diagnostic odds ratio (DOR) and risk of bias analysis were performed. Meta-analysis was performed using MedCalc software, and suitable parameters to assess heterogeneity were computed. Results: Twelve randomized clinical trials with a total of 1,681 TS patients were included as per the inclusion criteria. The patients’ clinical symptoms were improved to a greater extent, and the pooled DOR of 1.311 with a 95% confidence interval (CI) value ranging from 0.804 to 2.139 and I² value of 72.04% were obtained. The pooled relative risk was 1.09, with a 95% CI value ranging from 0.97 to 1.268. The data heterogeneity was assessed, and we achieved a Q value of 33.54, a p value of 0.0004, and I² value of 67.21% with a 95% CI value of 32.91–82.10. All these values are statistically significant, with p < 0.005, and confirmed the effectiveness of TCM for TS patients. Conclusion: The present meta-analysis on account of these statistically significant results highly recommends using TCM to treat TS.

Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion.

Background: Tourette syndrome (TS) is a neuropsychiatric disorder with onset in childhood that warrants effective therapies. Gut microbiota can affect central physiology and function via the microbiota–gut-brain axis. Therefore, the gut microbiota plays an important role in some mental illnesses. A small clinical trial showed that fecal microbiota transplantation (FMT) may alleviate TS symptoms in children. Herein, FMT effects and mechanisms were explored in a TS mouse model.Methods: TS mice model (TSMO) (n = 80) were established with 3,3′-iminodipropionitrile, and 80 mice were used as controls. Mice were grouped into eight groups and were subjected to FMT with feces from children or mice with or without TS, or were given probiotics. Fecal specimens were collected 3 weeks after FMT. 16S rRNA sequencing, behavioral observation, and serum serotonin (5-HT) assay were performed. Differences between groups were analyzed using Mann-Whitney U test and Kolmogorov-Smirnov (KS) tests.Results: A total of 18 discriminative microbial signatures (linear discriminant analysis score > 3) that varied significantly between TS and healthy mice (CONH) were identified. A significant increase in Turicibacteraceae and Ruminococcaceae in TSMO after FMT was observed (P < 0.05). Compared with non-transplanted TSMO, the symptoms of those transplanted with feces from CONH were alleviated (W = 336, P = 0.046). In the probiotic and FMT experiments, the serum 5-HT levels significantly increased in TSMO that received probiotics (KS = 1.423, P = 0.035) and in those transplanted with feces from CONH (W = 336.5, P = 0.046) compared with TSMO without transplantation.Conclusions: This study suggests that FMT may ameliorate TS by promoting 5-HT secretion, and it provides new insights into the underlying mechanisms of FMT as a treatment for TS.

Efficacy of Behavioural Intervention, Antipsychotics, and Alpha Agonists in the Treatment of Tics Disorder in Tourette's Syndrome.

Tourette's Syndrome (TS), in which patients have sudden, repeated, involuntary twitches and movements, called tics, is a condition of the nervous system. They can be motor, vocal, simple, or complex tics. It can be physically, emotionally, mentally, and socially distressing and challenging for those suffering from it. Usually, it is accompanied by various comorbidities like attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and sleep disorders. A variety of environmental and genetic factors are also associated with tics in TS like the first-degree relatives are more at risk of developing TS.TS is heterogeneous with complicated patterns of inheritance and phenotypic manifestations. There is a strong association between common single nucleotide polymorphisms (SNP, s) in the SLITRK1 gene and TS. Environmental factors like prenatal, postnatal, and perinatal factors directly influence tics in TS. These factors are low birth weight, intrauterine growth retardation (IGR), and various infections. The treatment of TS can be broadly classified into non-pharmacological and pharmacological treatment. Non-pharmacological therapy includes various behavioural interventions that can be helpful in situations when patients are tolerant of medical treatments. Psychoeducation and counselling play an essential role in the treatment of TS. It is vital to give a proper understanding to the patient and their family about the disease. Cognitive-behavioral intervention for tics, cognitive-behavioral therapy, exposure and response prevention, relaxation techniques, deep brain stimulation, and habit reversal training are the commonly used therapies for tics. These therapies have shown good efficacy because it improves the Yale Global Tic Severity Scale score (YGTSS) significantly. And they show effectiveness in patients who are irresponsive to medical treatment. The main lines of medical treatment are antipsychotics and alpha agonists. Typical (haloperidol, pimozide) or atypical (aripiprazole, risperidone, olanzapine) Antipsychotics differ in their side effects, efficacy, and tolerance in different age groups of children. Haloperidol was the first drug approved by the Food and Drug Administration for tics, but later on, new developments and improvements were made as far as drug therapy is concerned. The alpha-agonist most commonly used is clonidine which is also available in the form of adhesive patches. Another alpha agonist which is also widely used is guanfacine. Botulinum toxin and baclofen have also shown efficacy in dealing with tics in TS with other comorbidities. We will review in this article all the main lines of treatment and their effectiveness in TS.