Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive-compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3-10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3-16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host's immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders.

Tic disorders (TD), including chronic/persistent TD (CTD) and Tourette syndrome, have been described and studied for many years. Within the last two decades, intensified study efforts led to more specific assumptions about genesis and influences of both hereditary and environmental factors. TD in children and adolescents are very often accompanied by attention-deficit/hyperactivity disorders and obsessive-compulsive disorders (OCD) as comorbid disorders. Comorbidities are aggravating factors concerning prognosis and treatment opportunities. Therefore, etiological considerations and treatment strategies have to take associated psychiatric disorders into account. Treatment approaches are symptom targeted and include behavioral treatments and/or medication and show positive outcomes concerning tic symptomatology, global functioning, and associated psychopathology. This review presents an update of the research, definitions, and classification according to ICD-10 and DSM-5 and summarizes the diagnostic procedures and most effective clinical strategies.

Aim To investigate the association between circulating anti‐dopamine D2 receptor (D2R) autoantibodies and the exacerbation of tics in children with chronic tic disorders (CTDs). Method One hundred and thirty‐seven children with CTDs (108 males, 29 females; mean age [SD] 10y 0mo [2y 7mo], range 4–16y) were recruited over 18 months. Patients were assessed at baseline, at tic exacerbation, and at 2 months after exacerbation. Serum anti‐D2R antibodies were evaluated using a cell‐based assay and blinded immunofluorescence microscopy scoring was performed by two raters. The association between visit type and presence of anti‐D2R antibodies was measured with McNemar’s test and repeated‐measure logistic regression models, adjusting for potential demographic and clinical confounders. Results At exacerbation, 11 (8%) participants became anti‐D2R‐positive (‘early peri‐exacerbation seroconverters’), and nine (6.6%) became anti‐D2R‐positive at post‐exacerbation (‘late peri‐exacerbation seroconverters’). The anti‐D2R antibodies were significantly associated with exacerbations when compared to baseline (McNemar’s odds ratio=11, p=0.003) and conditional logistic regression confirmed this association (Z=3.49, p<0.001) after adjustment for demographic and clinical data and use of psychotropic drugs. Interpretation There is a potential association between immune mechanisms and the severity course of tics in adolescents with CTDs.

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