New Insights in Neurobiology and Genetics of Tourette Syndrome

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Molecular and Cellular Neuroscience".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 14515

Special Issue Editors

Department of Neurology and Neurosurgery, Montreal Neurological Institute - Hospital, McGill University, Montréal, QC H3A 2B4, Canada
Interests: human genetics; neurogenomics; neurodevelopmental disorders; molecular genetics; complex traits
Special Issues, Collections and Topics in MDPI journals
Department of Neurology, Wuhan Children’s Hospital, Huazhong University of Science and Technology, Wuhan 430015, China
Interests: pediatric neurology; neurodevelopmental disorders; tics disorders; Tourette syndrome; clinical neurosciences
Beijing Anding Psychiatric Hospital, Capital Medical University, Beijing 100088, China
Interests: pediatric psychiatry; Tourette syndrome; attention deficit hyperactivity disorder (ADHD);, obsessive-compulsive disorder; psychiatric sciences

Special Issue Information

Dear colleagues,

Tourette syndrome is a common neurodevelopmental disorder affecting about 1% of school-age children and adolescents. Currently, there is still no single most effective treatment, despite decades of basic and clinical research efforts. However, recent advanced technologies in genomics research, brain imaging, neuropharmacology, and molecular neurobiology have greatly facilitated research progress in neurodevelopmental disorders, including Tourette syndrome and its comorbid neuropsychiatric disorders.

This Special Issue of Brain Sciences aims to present a collection of studies focusing on the most recent progresses in the field of Tourette syndrome research. Authors are invited to submit cutting-edge reviews, research articles, and meta-analysis of large existing datasets, which lead us towards a better understanding of the etiology and pathogenic mechanism of Tourette syndrome. The topics may include, but are not limited to, studies in epidemiology, neuropsychology and neurobehavior, genetics and genomics, brain imaging, molecular neurobiology, experimental model, and novel clinical investigation. The main format of the publication should be full-length Review and Original Article, but other formats with reduced length could also be considered, such as Brief Report, Short Note, Communication, or Commentary, as long as the manuscript provides innovative and insightful content that fits well with the theme of this Special Issue.

Prof. Dr. Lan Xiong
Prof. Dr. Zhi-sheng Liu
Prof. Dr. Yi Zheng
Guest Editors

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Keywords

  • Tourette syndrome
  • tics disorder
  • genetics
  • neurobiology
  • pathogenesis

Published Papers (7 papers)

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Research

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8 pages, 246 KiB  
Article
Influence of Tiapride and Topiramate on Tic Severity and Behavioral/Emotional Problems in Children with Tourette Syndrome: A Retrospective Study
by Xuanzi Zhou, Zhaoying Liao, Yi Li, Nanqing Wang and Nong Xiao
Brain Sci. 2023, 13(3), 383; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci13030383 - 22 Feb 2023
Viewed by 1119
Abstract
Objectives: To investigate the effect of tiapride and topiramate on patients with Tourette syndrome (TS). Methods: This retrospective analysis included 126 children diagnosed with TS at Children’s Hospital of Chongqing Medical University from 2019 to 2021, with treatment including tiapride (n = 60) [...] Read more.
Objectives: To investigate the effect of tiapride and topiramate on patients with Tourette syndrome (TS). Methods: This retrospective analysis included 126 children diagnosed with TS at Children’s Hospital of Chongqing Medical University from 2019 to 2021, with treatment including tiapride (n = 60) and topiramate (n = 66). Their tic severity values were assessed with the Yale Global Tic Severity Scale (YGTSS). Furthermore, behavioral and emotional problems were assessed with the Conner’s Parent Rating Scale (CPRS) and the Children Behavior Checklist (CBCL). Results: Compared with premedication, the scores of tic severity were significantly decreased in both tiapride and topiramate groups after treatment, especially topiramate. Moreover, it was noted that five subscores of CPRS were significantly reduced in TS patients thanks to medication. However, there was no significant difference in CBCL after treatment, in both tiapride and topiramate groups. Conclusions: Tiapride and topiramate were proven to be effective on tics and some behavioral/emotional problems in TS patients, and topiramate may provide better treatment. Full article
(This article belongs to the Special Issue New Insights in Neurobiology and Genetics of Tourette Syndrome)
10 pages, 856 KiB  
Article
A Pilot Study on Plasma and Urine Neurotransmitter Levels in Children with Tic Disorders
by Qiao-Qiao Qian, Qian-Qian Tan, Dan Sun, Qing Lu, Ying-Ying Xin, Qian Wu, Yong Zhou, Yang-Xi Liu, Pei-Chao Tian and Zhi-Sheng Liu
Brain Sci. 2022, 12(7), 880; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12070880 - 04 Jul 2022
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Abstract
Background: Tic disorders (TDs), including Tourette syndrome, are childhood-onset neuropsychiatric disorders characterized by motor and/or vocal tics that commonly affect children’s physical and mental health. The pathogenesis of TDs may be related to abnormal neurotransmitters in the cortico-striatal-thalamo-cortical circuitry, especially dopaminergic, glutamatergic, and [...] Read more.
Background: Tic disorders (TDs), including Tourette syndrome, are childhood-onset neuropsychiatric disorders characterized by motor and/or vocal tics that commonly affect children’s physical and mental health. The pathogenesis of TDs may be related to abnormal neurotransmitters in the cortico-striatal-thalamo-cortical circuitry, especially dopaminergic, glutamatergic, and serotonergic neurotransmitters. The purpose of this study was to preliminarily investigate the differences in the three types of neurotransmitters in plasma and urine between children with TD and healthy children. Methods: We collected 94 samples of plasma and 69 samples of urine from 3–12-year-old Chinese Han children with TD before treatment. The plasma and urine of the same number of healthy Chinese Han children, matched for age and sex, participating in a physical examination, were collected. Ultra-performance liquid chromatography-tandem mass spectrometry was used to detect the three types of neurotransmitters in the above samples. Results: The plasma levels of norepinephrine, glutamic acid, and γ-aminobutyric acid, and the urine levels of normetanephrine and 5-hydroxyindoleacetic acid were higher in the TD children than in healthy children. The area under the curve (AUC) values of the above neurotransmitters in plasma and urine analyzed by receiver operating characteristic curve analysis were all higher than 0.6, with significant differences. Among them, the combined AUC of dopamine, norepinephrine, normetanephrine, glutamic acid, and γ-aminobutyric acid in the 8–12-year-old subgroup was 0.930, and the sensitivity and specificity for TD were 0.821 and 0.974, respectively (p = 0.000). Conclusions: There are differences in plasma and urine neurotransmitters between TD children and healthy children, which lays a foundation for further research on the pathogenesis of TD. Full article
(This article belongs to the Special Issue New Insights in Neurobiology and Genetics of Tourette Syndrome)
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14 pages, 2498 KiB  
Article
Micro-RNAs from Plasma-Derived Small Extracellular Vesicles as Potential Biomarkers for Tic Disorders Diagnosis
by Yilong Wang, Xuebin Xu, Haihua Chen, Mengying Zhu, Xiaotong Guo and Feng Gao
Brain Sci. 2022, 12(7), 829; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12070829 - 26 Jun 2022
Cited by 2 | Viewed by 2000
Abstract
Tic disorders (TDs) are a series of childhood neuropsychiatric disorders characterized by involuntary motor and/or vocal tics and commonly comorbid with several other psychopathological and/or behavioral disorders (e.g., attention deficit hyperactivity disorder and obsessive–compulsive disorder), which indeed aggravate clinical symptoms and complicate diagnosis [...] Read more.
Tic disorders (TDs) are a series of childhood neuropsychiatric disorders characterized by involuntary motor and/or vocal tics and commonly comorbid with several other psychopathological and/or behavioral disorders (e.g., attention deficit hyperactivity disorder and obsessive–compulsive disorder), which indeed aggravate clinical symptoms and complicate diagnosis and treatment. Micro-RNAs (miRNAs) derived from small extracellular vesicles (sEVs) have been recognized as novel circulating biomarkers of disease. To identify specific miRNAs derived from plasma sEVs for TDs’ diagnosis and prognosis, we used official EV isolation and purification methods to characterize the plasma-derived EV miRNAs from children with different types of TDs. Nanoparticle tracking analysis, transmission electron microscopy, and immunoblot analysis of EV surface markers were applied to confirm the features and quality of sEVs. The RNA sequencing (RNA-seq) approach was adapted to identify novel circulating sEVs-derived miRNAs with altered expression levels in paired comparisons of TDs versus healthy controls (HCs), transient tic disorder (TTD) versus chronic motor or vocal tic disorder (CTD), and TTD versus Tourette Syndrome (TS). GO term and KEGG pathway were performed for functional analysis and the receiver operator curve analysis was followed to test the diagnosis efficacy of differentially expressed miRNAs (DEMs) derived from plasma sEVs among paired groups, namely, TDs versus HCs, TTD versus CTD, and TTD versus TS. As a result, 10 miRNAs (hsa-let-7a, hsa-let-7b, hsa-let-7c, hsa-let-7e, hsa-let-7f, hsa-miR-25-3p, hsa-miR-29a-3p, hsa-miR-30b-5p, hsa-miR-125b-5p, and hsa-miR-1469) have demonstrated a significantly different expression signature in the TDs group compared to HCs with excellent area under curve (AUC) values of 0.99, 0.973, 0.997, 1, 0.99, 0.997, 0.987, 0.993, 0.977, and 0.997, respectively, and the diagnostic efficacy of miRNAs was also estimated for discriminating TTD from CTD or TS. In our research, we finally obtained several potential sEVs-derived miRNA biomarkers to assess the diagnosis and prognosis of TDs. Full article
(This article belongs to the Special Issue New Insights in Neurobiology and Genetics of Tourette Syndrome)
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9 pages, 224 KiB  
Article
Identifying Factors Associated with the Recurrence of Tic Disorders
by Yixin Zhang, Nong Xiao, Xilian Zhang, Zhenhua Zhang and Jiusi Zhang
Brain Sci. 2022, 12(6), 697; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12060697 - 27 May 2022
Cited by 1 | Viewed by 1810
Abstract
Tic disorders are neurological disorders that are prone to fluctuation and recurrence. It is important to study the factors related to disease recurrence and to subsequently provide suggestions for clinical treatment. A retrospective study was conducted to assess patients with recurrent and non-recurring [...] Read more.
Tic disorders are neurological disorders that are prone to fluctuation and recurrence. It is important to study the factors related to disease recurrence and to subsequently provide suggestions for clinical treatment. A retrospective study was conducted to assess patients with recurrent and non-recurring tic disorders diagnosed in the Pediatric Tic Disorder Clinic of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, China, and to extract various factors—such as fetal status; medication, allergy, and family history; social and psychological factors; blood lead content; electroencephalogram (EEG); disease duration; type of tics; and disease severity—and identify factors associated with recurrence. The recurrence rate of tic disorders was approximately 45.10% in this study. The childbirth conditions, surgery/trauma, respiratory tract infection, allergy, stress, consumption of tiapride, and severity of tic disorders were factors related to and affected disease recurrence. Full article
(This article belongs to the Special Issue New Insights in Neurobiology and Genetics of Tourette Syndrome)
12 pages, 1730 KiB  
Article
The Prevalence and Comorbidity of Tic Disorders and Obsessive-Compulsive Disorder in Chinese School Students Aged 6–16: A National Survey
by Junjuan Yan, Hu Deng, Yongming Wang, Xiaolin Wang, Tengteng Fan, Shijie Li, Fang Wen, Liping Yu, Fang Wang, Jingran Liu, Yuanzhen Wu, Yi Zheng, Yonghua Cui and Ying Li
Brain Sci. 2022, 12(5), 650; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12050650 - 16 May 2022
Cited by 6 | Viewed by 2271
Abstract
Background: Obsessive-compulsive disorder (OCD) and tic disorders (TDs) are closely related and considered to etiologically overlap. Both disorders are characterized by repetitive behaviors. TD and OCD often co-occur. The high comorbidity between OCD and TD individuals suggests that we also need to pay [...] Read more.
Background: Obsessive-compulsive disorder (OCD) and tic disorders (TDs) are closely related and considered to etiologically overlap. Both disorders are characterized by repetitive behaviors. TD and OCD often co-occur. The high comorbidity between OCD and TD individuals suggests that we also need to pay more attention to the homogeneity and heterogeneity between TS and OCD. To date, there has been no systematic nationwide epidemiological survey of the mental health (including tic disorders and obsessive-compulsive disorder) of children and adolescents in China. Methods: A two-stage epidemiological study of psychiatric point prevalence was conducted. We used the multistage cluster stratified random sampling strategy to assess five provinces of China. The Child Behavior Checklist was used to identify behavioral problems among the enrolled students in the first stage. The results from the Mini-International Neuropsychiatric Interview for Children and Adolescents and evaluations from two psychiatrists based on the Diagnostic and Statistical Manual-IV were used to make a diagnosis. Point weighted prevalence for TD and OCD was estimated. We adjusted prevalence estimates with the product of sampling weights and poststratification weights. Standard error values and 95% confidential intervals were generated with Taylor series linearization. Rao–Scott adjusted chi-square (χ2) tests were employed to compare the prevalence estimates of different age and sex groups. Results: In the first stage, 73,992 participants aged 6–16 years old were selected. The prevalence rates of OCD and TDs were 1.37% (95% CI: 1.28–1.45) and 2.46% (95% CI: 2.35–2.57), respectively. The prevalence of OCD was found to be higher in girls (p < 0.001) and higher in boys with transient tic disorder (TTD) (p < 0.001) and Tourette’s syndrome (TS) (p < 0.001). The most common comorbidity of TS was OCD (40.73%), and for OCD, it was TS (11.36%). Conclusions: Our study is the first nationwide survey on the prevalence of TD (2.46%) and OCD (1.37%) in school students aged 6–16 years old in China. The high comorbidity between OCD and TD individuals suggested overlap based on the prevalence dimensions, which might be influenced by age and sex. This result suggested that we also need to pay more attention to the homogeneity and heterogeneity between TS and OCD. Full article
(This article belongs to the Special Issue New Insights in Neurobiology and Genetics of Tourette Syndrome)
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Review

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18 pages, 3362 KiB  
Review
P3b Amplitude and Latency in Tic Disorders: A Meta-Analysis
by Yue Yang, Hua Yang, Yao Deng, Tao Yu and Rong Luo
Brain Sci. 2022, 12(12), 1712; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12121712 - 14 Dec 2022
Viewed by 1344
Abstract
P3b is an event-related potential (ERP) that may be abnormal in patients with tic disorders (TD), but evidence has been inconsistent. Given the possible association between P3b and TD and the need for biomarkers for TD, the primary objective of this meta-analysis was [...] Read more.
P3b is an event-related potential (ERP) that may be abnormal in patients with tic disorders (TD), but evidence has been inconsistent. Given the possible association between P3b and TD and the need for biomarkers for TD, the primary objective of this meta-analysis was to characterize P3b in patients with TD in comparison to healthy controls (HCs). Methods: By searching PubMed, Embase, Web of Science, SCOPUS, Medline, and Google Scholar, we identified studies that compared P3b between TD patients and HCs. The amplitude and latency of P3b were then analyzed. Subgroup analyses were conducted to investigate the influence of different experimental factors on P3b indices. Result: Overall, 19 articles involving 388 cases and 414 controls were evaluated. There were no significant abnormalities in P3b amplitude and latency in TD patients. The P3b amplitude of the TD patients was significantly decreased during the oddball task, and the P3b amplitude of the adult TD patients was also significantly decreased. Conclusion: TD patients may have an abnormal P3b compared to HCs under specified conditions. Full article
(This article belongs to the Special Issue New Insights in Neurobiology and Genetics of Tourette Syndrome)
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15 pages, 434 KiB  
Review
The Aetiology of Tourette Syndrome and Chronic Tic Disorder in Children and Adolescents: A Comprehensive Systematic Review of Case-Control Studies
by Jilong Jiang, Mengxin Chen, Huifang Huang and Yanhui Chen
Brain Sci. 2022, 12(9), 1202; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12091202 - 06 Sep 2022
Cited by 1 | Viewed by 1967
Abstract
(1) Introduction: Tourette syndrome (TS) and chronic tic disorder (CTD) are common neurodevelopmental/-psychiatric disorders. The aetiological factors that contribute to the pathogenesis of TS/CTD are still poorly understood. The possible risk factors for TS/CTD are considered to be a combination of genetic, immunological, [...] Read more.
(1) Introduction: Tourette syndrome (TS) and chronic tic disorder (CTD) are common neurodevelopmental/-psychiatric disorders. The aetiological factors that contribute to the pathogenesis of TS/CTD are still poorly understood. The possible risk factors for TS/CTD are considered to be a combination of genetic, immunological, psychological and environmental factors. A comprehensive systematic review was conducted to assess the association between aetiological factors and TS/CTD. (2) Methods: Electronic databases, including PubMed, Embase, Web of Science, Wanfang data, and CNKI, were searched to identify the etiological factors of children and adolescents (≤18 years) with TS/CTD based on a case-control study. Quality assessments were performed according to the Newcastle-Ottawa scale (NOS). (3) Results: According to sample sizes and NOS values, recent evidence may support that genetic factors (BTBD9 and AADAC), immunological factors (streptococcus and mycoplasma pneumoniae infections), environmental factors (conflict, history of perinatal diseases, and family history of neurological and psychiatric diseases and recurrent respiratory infections) and psychological factors (major life events) are associated with the pathogenesis of TS/CTD. (4) Conclusions: Some risk factors in different categories may be the etiological factors of TS/CTD, but there is a lack of studies on the interaction among the factors, which may require more attention in the future. Full article
(This article belongs to the Special Issue New Insights in Neurobiology and Genetics of Tourette Syndrome)
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