European Multicentre Tics in Children Studies (EMTICS): protocol for two cohort studies to assess risk factors for tic onset and exacerbation in children and adolescents

Anette Schrag, Davide Martino, Alan Apter, Juliane Ball, Erika Bartolini, Noa Benaroya-Milshtein, Maura Buttiglione, Francesco Cardona, Roberta Creti, Androulla Efstratiou, Maria Gariup, Marianthi Georgitsi, Tammy Hedderly, Isobel Heyman, Immaculada Margarit, Pablo Mir, Natalie Moll, Astrid Morer, Norbert Müller, Kirsten Müller-Vahl, Alexander Münchau, Graziella Orefici, Kerstin J. Plessen, Cesare Porcelli, Peristera Paschou, Renata Rizzo, Veit Roessner, Markus J. Schwarz, Tamar Steinberg, Friederike Tagwerker Gloor, Zsanett Tarnok, Susanne Walitza, Andrea Dietrich, Pieter J. Hoekstra, EMTICS Collaborative Group

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.