Cross-sectional Study of Dopamine-2 Receptor Antibodies in Patients with Tourette Syndrome and Obsessive-Compulsive Disorder

Grant Type
Clinical
Grant Year
2013-2014
Institution Location
Foreign
Institution Organization Name
Children’s Hospital at Westmead, University of Sydney, Australia
Investigators Name
Dale, Russell C., PhD, MD

Over the last decade it has become apparent that Tourette syndrome (TS) is a heterogeneous entity rather than a single disease. Aetiological models now include genetic and environmental factors in the generation of disease, and TS neurobiology also proposes a role for the dopaminergic signalling pathway. The existence of an autoimmune subgroup in Tourette syndrome (TS) has been a controversial, but exciting hypothesis. There have been many published papers exploring the existence of autoantibodies in Tourette syndrome, but conclusive data have been lacking so far. However, most previous studies have used antibody methodologies that are unlikely to be involved in a pathogenic autoantibody process. Recent paradigms in autoantibody research state that pathogenic antibodies bind to extracellular domains of important neuronal receptors. We have recently discovered that a subgroup of patients with TS have autoantibodies to surface dopamine-2 receptor (D2R), a receptor essential for the control of movement and behaviour. Interestingly, D2R is the target of psychiatric drugs observed to improve TS and obsessive-compulsive disorder (OCD) symptoms. We propose to use a large cohort of 300 patients with TS and OCD to define the proportion and clinical characteristics of patients with TS who are positive for D2R antibodies. This biomarker could define patients who will benefit from immune therapy. The goals of the study: 1. To define the proportion of patients with Tourette syndrome and obsessive-compulsive disorder who are positive for D2R antibodies using a large cross-sectional cohort of patients. 2. To determine the demographics and clinical endophenotype of patients with positive D2R antibodies. Russell C. Dale, Ph.D., M.D. & Fabienne Brilot, Ph.D. Children’s Hospital at Westmead, University of Sydney, Australia Award: $75,000 Tourette Association of America Inc. – Research Grant Award 2013-2014