The Aetiology of Tourette Syndrome and Chronic Tic Disorder in Children and Adolescents: A Comprehensive Systematic Review of Case-Control Studies

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, 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.

Cytokine expression profiles in children and adolescents with tic disorders

“…An increase in TNF-α levels may increase the permeability of the blood‒brain barrier and lead to an enhanced autoimmune response, along with greater dopamine release in the basal ganglia, potentially contributing to the clinical symptoms of TS and related disorders 38 – 40 . Notably, TNF-α and IL-6 levels were significantly increased in the peripheral blood of patients with Tourette’s in a recent meta-analysis 5 .…”

“…Tic disorders in the DSM-5 include Tourette Syndrome (TS), persistent (chronic) motor/vocal tic disorder (CMVTD), and provisional tic disorder 1 , 2 . The consensus is that these disorders arise due to impaired function of the cortical-striatal-thalamic-cortical circuits, and aberrations of associated neurotransmitters may include dopamine, serotonin, gamma-aminobutyric acid (GABA), glutamate, acetylcholine, noradrenaline, and histamine 3 – 5 . The etiology of tic disorders is complex and involves multiple genetic, environmental, psychological, and immunological factors as well as their interactions 3 – 5 .…”

“…These implicated potassium channels, membrane proteins, histidine metabolism, mitochondrial functioning, dopaminergic, GABAergic, and monoamine neurotransmitter function in etiology 3 – 6 . Genome wide association studies (GWAS) as well as studies evaluating single nucleotide polymorphisms (SNPs) suggest that tic disorders are polygenetic and the interaction between genetic predisposition and environmental factors increase the risk of their occurrence 3 – 5 , 7 .…”

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

“…TS is a heterogeneous disease with a multifactorial pathogenesis. The possible pathogenesis of TS is generally considered to be a combination of genetic, immunological, environmental, and psychological factors ( 4 ).…”

“…In the past 2 decades, the relationship between immune activation, infection, and TS have been widely studied ( 4 - 7 ). These studies focused on infections as a possible contributing factor in TS, particularly those caused by group A Streptococcus (GAS) and mycoplasma pneumonia (MP) ( 8 , 9 ).…”