title: Association of Tic Disorders and Enterovirus Infection: A Nationwide Population-Based Study.
abstract: There has been growing interest in the association between infectious disease and mental disorders, but an association between enterovirus (EV) infection and tic disorders has not been sufficiently explored. Herein, we aim to investigate the association between EV infection and incidence of tic disorders in a nationwide population-based sample using Taiwan's National Health Insurance Research Database. We identified individuals aged ≤18 years prior to 2005 with an inpatient diagnosis of EV infection and/or history of EV infection. Tic disorder was operationalized using International Classification of Disease, Revision 9, Clinical Modification (ICD-9-CM) codes 307.20-307.23. A total of 47,998 individuals with history of EV infection were compared to 47,998 sex-, age-, and urbanization-matched controls on incidence of tic disorders. The mean ± standard deviation follow-up period for all subjects was 9.7 ± 3.6 years; the mean latency period between initial EV infection and incident diagnosis of tic disorder diagnosis was 5.4 ± 2.8 years. EV infection was significantly associated with greater incidence of tic disorders (hazard ratio [HR] = 1.24, 95% CI: 1.07-1.45). When subgrouped on the basis of central nervous system (CNS) involvement, EV infection with CNS involvement was not significantly associated with greater incidence of tic disorders when compared to controls (HR = 1.25, 95% CI: 0.64-2.43); EV infection without CNS involvement was significantly associated greater incidence of tic disorders when compared to controls (HR = 1.24, 95% CI: 1.07-1.45). In addition, hospitalization for an EV infection did not increase the hazard for greater incidence of tic disorders (HR = 1.32, 95% CI: 1.04-1.67 with hospitalization and 1.22, 95% CI: 1.04-1.44 without hospitalization). EV infection is temporally associated with incidence of tic disorders. Our observations add to the growing body of literature implicating immune-inflammatory system in the pathoetiology of brain disorders in a subpopulation of individuals and serve as a clarion call for surveillance of symptoms suggestive of tic disorders in individuals with history of EV infection.
authors.affiliation: From the Department of Psychiatry, Chang Gung Memorial Hospital and University, Chiayi (C-ST, VC-HC); Graduate Institute of Clinical Medical Sciences, Chang Gung University (C-ST, VC-HC); Chang Gung Institute of Technology, Taoyuan (C-ST); Department for Traditional Chinese Medicine (Y-HY); Center of Excellence for Chang Gung Research Datalink, Chang Gung Memorial Hospital, Chiayi (Y-HY); Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei (Y-HY), Department of Speech, Language Pathology and Audiology, Chung Shan Medical University, Taichung, Taiwan (K-YH); and Department of Psychiatry, University of Toronto, Mood Disorders Psychopharmacology Unit, University Health Network (YL, RSM), Toronto, Ontario, Canada.
authors.forename: Ching-Shu
authors.initials: CS
authors.lastname: Tsai
authors.forename: Yao-Hsu
authors.initials: YH
authors.lastname: Yang
authors.forename: Kuo-You
authors.initials: KY
authors.lastname: Huang
authors.forename: Yena
authors.initials: Y
authors.lastname: Lee
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
authors.forename: Vincent Chin-Hung
authors.initials: VC
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D004769:Enterovirus Infections / Q000453:epidemiology*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology; D015994:Incidence; D007223:Infant; D008297:Male; D009313:National Health Programs / Q000706:statistics & numerical data; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology; D016016:Proportional Hazards Models; D012111:Residence Characteristics; D012737:Sex Factors; D013624:Taiwan / Q000453:epidemiology; D013981:Tic Disorders / Q000453:epidemiology*; D005879:Tourette Syndrome / Q000453:epidemiology