Tic Disorders

 

CAPPLab

Child and Adolescent Psychopathology

Tic Disorders

 

Tourette syndrome (TS) is an inherited neurological disorder characterized by the presence of multiple sudden, rapid, recurrent, and non-rhythmic movements (motor tics) and/or utterances (vocal/phonic tics). While initially considered rare, the prevalence is now estimated to be 0.3-1% (between 3 in 1000 and 1 in 100 people) worldwide, affecting predominantly children. Symptoms appear before the individual is 18 years old and can affect people of all ethnic groups, whereas males are affected 3 to 4 times more often than females.

 

The etiology of tic disorders and associated obsessive-compulsive and behavioral symptoms is poorly understood. It has been postulated that genetic and environmental factors affecting regulatory systems (e.g. immune and endocrine systems) might interact in creating a neurobiological vulnerability to the development of tics and associated behaviors.

 

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 Group A beta-haemolytic Streptococcus (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. Based on this the Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections [PANDAS]-hypothesis came up.

 

Despite many efforts to date, the understanding of disease pathophysiology of Tic disorders is poor, which is reflected in the limited availability of therapeutic options to successfully manage tics and associated neuropsychiatric symptoms in affected individuals. All current psychopharmacological treatment options of Tic disorders may just diminish tics but cannot heal them (Robertson, 2000; McNaught and Mink, 2011). In order to discover novel treatments and effective preventative methods there is a pressing need to understand the complex disease pathophysiology of tic disorders.

Tic-Treatment

In the treatment of tics, both pharmacological and behavioral therapeutic approaches are successfully applied. For both forms of intervention evaluation studies with positive results exist. However direct comparative data showing whether and to what extent a pharmacological intervention with tiapride is preferable to the behavioral intervention by Habit reversal training in terms of their short- and long -term efficacy and safety, or vice versa. The aim of the proposed study is therefore to investigate the short-term effects of both forms of therapy for the first time comparatively. In this study, both affected and healthy children aged 10 to 17 years are examined. In affected individuals, the indication for treatment of their tic disorder should be provided and the choice of therapy is left to the study participants and their parents. The study comprises two EEG dates at intervals of 10 weeks (before and 10 weeks after the successful Tiaprid- or Habit reversal therapy).

EMTICS

The aim of EMTICS (European Multicenter Tics in Children Study) is to explore this 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. The study seeks 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.

EMTICS consists of two large-scale multicenter longitudinal cohort studies, entitled ONSET and COURSE, which involve affected patients and at-risk first-degree relatives within an integrated, multidisciplinary research strategy. ONSET, a 3 year longitudinal observational study, considers children aged from 3-10 years, who are siblings or off-spring of patients with a chronic tic disorder, but have not manifested tics or obsessive compulsive symptoms at the time of study enrolment. 302 participants shall be included. COURSE, a 16 month longitudinal observational study, considers children and adolescents aged from 3-16 years with an already diagnosed chronic tic disorder. 700 participants shall be included. Both environmental factors (such as the experience of psychosocial stress and the occurrence of infections) and biomarkers (such as immunological alterations, gene expression changes and infectious parameters) that are potentially linked to tic exacerbations, are recorded at three time points: during baseline, follow-ups and the final visit.

The EMTICS consortium brings together experts in the field of tic disorders across Europe. This project received funding from the 'European Community's Seventh Framework Programme' (FP7/2007-2013). The coordinator is Dr. Pieter Hoekstra from the University Medical Center, Dept. of Child and Adolescent Psychiatry, Groningen (The Netherlands).

See also: www.emtics.eu

TICGenetics

The TICGenetics study brings the complex genetics of tic disorders more into focus. Despite decades of evidence supporting a significant genetic contribution, progress in identifying genetic risk alleles has been slow (State, 2011). This difficulty is thought to be a consequence of complex inheritance pattern and substantial genetic and phenotypic (symptom) heterogeneity (Fernandez et al., 2012; Moya et al., 2013; Moya et al., 2013). For this reason, TICGenetics was established, in an effort to better understand the biological causes of TS and associated disorders.

Information from approximately 2000 persons who either have TS or are related to someone with TS is gathered, in order to make this research possible (Dietrich et al., 2014). Therefore either families with only one affected child (simplex families) or families with at least three people with TS and/or OCD (multiplex families) are considered. Besides anamnestic and psychiatric information of each family member, blood samples for genetic analysis are collected.

The Tourette International Collaborative Genetics (TIC Genetics) Study includes scientists and clinicians specialized in Tourette Syndrome (TS) from more than 20 sites across the United States, Europe, and South Korea. The project is funded by the National Institute of Mental Health (NIMH) in the USA.

See also: www.tic-genetics.org