Neurocognitive endophenotypes of obsessive compulsive disorder and their brain correlates

• Applicants: Professor Dr. Norbert Kathmann; Professor Michael Wagner, Ph.D.
• Subject Area: Personality Psychology, Clinical and Medical Psychology, Methodology
• Term: from 2014 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 249236207

The causes for obsessive-compulsive disorder (OCD) are insufficiently known. This is probably due to the limited etiological validity of the clinical-phenomenological description of the disorder. Despite strong evidencefor heritability of obsessive-compulsive traits and disorder in twin and family studies only weak associations with gene variants have been established so far. Endophenotypes (EPT) for mental disorders are quantitativebiological or cognitive traits that are closer to the biological underpinnings than the clinical syndrome itself. Therefore, they are expected to make the search for relevant genes more efficient, to facilitate the detection of interacting psychological factors, and, generally, to foster the development of better pathogenetic models and better therapies. At present, there is highly promising evidence for three EPT candidates for OCD. Those are 1. Event-related brain potential correlates of action monitoring, 2. Saccadic indicators of endogenuous action initiation, and 3. behavioral indicators of motor response inhibition. However, these EPT candidates have been confirmed in small sample studies only, and their relation to symptom dimensions and subtypes of OCD as well as to their neural underpinnings remains unclear as yet. We plan to further analyse the three candidates using an adequately large sample, in order to a) confirm them as reliable EPTs of OCD, b) relate them specifically to OCD symptom dimensions and age at disease onset, and c) test the relationship of the EPT candidates to structural and functional brain measures. As a future perspective, associations of confirmed EPT variables with candidate gene variants will be tested, and longitudinal studies focusing on the effects of EPTs will be conducted. In the present project, we aim to compare 200 patients with OCD, 200 first-degree relatives of OCD patients, and 200 healthy comparison subjects. A main strength of the present approach is its reexamination and extension of relevant findings with sufficient power and the integration into a coherent model. The present project will be conducted in two research centers (Berlin, Bonn), is based on promising and substantial pilot studies and combines the research and methodological expertise of the two contributing research groups.

• DFG Programme: Research Grants