European Multicentre Tics in Children Study

The aetiology of tic disorders and associated obsessive-compulsive and
behavioural symptoms is poorly understood. It has been postulated that genetic
and environmental factors active upon regulatory systems (e.g. immune and
endocrine systems) might interact in creating a neurobiological vulnerability
to the development of tics and associated behaviours. The largest body of
evidence from clinical research has been gathered in support of a role of
exposure to psychosocial stress, of pregnancy and delivery adversities and of
infections from GAS (Murphy, Kurlan, and Leckman, 2010). The human pathogen GAS
is a major cause of common pharyngitis, but also of significant
post-streptococcal non-suppurative autoimmune multi-organ sequelae associated
with the existence of host autoantibodies against GAS antigens (also known as
the Paediatric Autoimmune Neuropsychiatric Disorders Associated with
Streptococcal Infections [PANDAS]-hypothesis). However, the mechanisms leading
to such vulnerability are still largely undefined.

To explore the complex interaction between environment, autoimmunity and
genetics in relation to the onset and clinical course of tic disorders and
associated obsessive-compulsive symptoms and to translate these findings into
clinical applications. We aim to identify the role of exposure to specific
environmental factors, including new exposure to specific molecular GAS types
and/or subtypes in the form of pharyngeal carriage or infection and
psychosocial stress on the onset and course of tics, as well as to identify the
human gene pathways that are activated upon symptom exacerbations, by
implementing longitudinal genome wide gene expression studies.

This is a longitudinal observational European multicenter study consisting of
an ONSET and COURSE study part. European sites together will recruit 375
children in the ONSET and 700 children in the COURSE study. The UMCG/de Bascule
will recruit respectively 25 and 45 children.

The burden will be completion of parent-questionnaires (maximal 11 x 20
minutes = 220 min), child-questionnaires (maximal 10 x 10 minutes = 100 min),
telephone interviews with the parent (maximal 9 x 20 minutes = 180 min),
completion of a weekly home diary by the parent (maximal 126 x 5 minutes = 630
min), and clinical evaluations (maximal 11 x 60 minutes = 660 min), blood draws
by venipuncture (maximal 10 times), throat swabs (maximal 4 times) and
collection of hair strands (maximal 10 times) in the child.
Risks and physical or physiological discomfort will be negligible.
Participation in the study will be of no benefit to individual patients,
however, the study will benefit the population at large, possibly helping the
participants* younger siblings and future families.
This research protocol includes the participation of minors. Tic disorders have
a childhood onset. Tics often lessen in intensity and frequency or may even
disappear in adulthood. To do a proper study it is unavoidable to also involve
minors.