Compulsivity in mouse strains homologous with chromosomes 7p and 15q linked to obsessive-compulsive disorder

Obsessivecompulsive disorder OCD is a severe anxiety disorder characterized by obsessions and compulsions. The core symptom of OCD is compulsivity, the inability to stop thinking or acting when you want to, despite being aware of the uselessness of the content or the adverse consequences. To initiate a systematic search for genetic mechanisms underlying the pathophysiology of compulsivity, a panel of chromosome substitution CS strains, derived from mice that suppress C57BL6J strain or maintain AJ strain high levels of repetitive wheel running during 2 hr of daily limited food access, was screened for this compulsive behavior. Following the genetic screen, we found linkage between compulsive wheel running and mouse chromosomes 2, 6, and 7 that show overlap with recently identified human linkage regions for OCD on chromosomes 7p and 15q. In the overlapping humanmouse genomic region, the CRH receptor 2 CRHR2 gene was tested in a human case–control study. An initial exploration in OCD cases versus controls failed to detect an association between fourcandidate CRH2R SNPs within this homologous linkage region and OCD. Genetic fine mapping of compulsivity in mice provides new opportunities to reveal mechanisms underlying this significant psychiatric trait. © 2009 WileyLiss, Inc.