Seeking out candidate endophenotypes for OCD. Neurocognitive findings in unaffected relatives.

Abstract

Background:Obsessive compulsive disorder (OCD) is a highly heritable neuropsychiatric disorder. Attempts to elucidate contributing genes have met with limited success. Intermediate markers of brain dysfunction (cognitive endophenotypes) may help focus the search for genetic contributions. Such markers should be present in people at risk of developing OCD in the absence of clinical symptoms. In prior work, OCD patients showed impairment on tests of response inhibition and cognitive flexibility (Chamberlain et al., 2005, 2006).Methods:First-degree relatives of OCD patients, patient probands, and matched healthy volunteers without a family history of OCD undertook neuropsychological assessment (n=20 per group).Results:Compared to matched controls without a family history of OCD, unaffected first-degree relatives of OCD patients showed impaired response inhibition (p<0.05) and cognitive flexibility (p<0.05). These deficits were comparable to those in the patients themselves.Conclusions:Brain-based cognitive markers of inhibitory functions may be of utility in the search for OCD endophenotypes. Examination of relationships between these abnormalities, genetics, and structural/functional brain changes, will help to elucidate aetiological contributions to OCD and putative spectrum disorders.