Neurobiology of obsessive–compulsive disorder: insights into neural circuitry dysfunction through mouse genetics

The precise causal factors for obsessive–compulsive disorder (OCD) are not known, although, decades of research have honed in on the cortico-striatal-thalamo-cortical (CSTC) circuitry in the brain as a critical pathway involved in obsessions and the intimately linked compulsive–repetitive behaviors. Recent progress in human and mouse genetics have led to the identification of novel candidate susceptibility genes, which in turn have facilitated a more focused approach to unraveling the nature of circuitry dysfunction in OCD. The ability to perform invasive techniques in genetic animal models of OCD will be crucial for rapid advances in this field, and as such we review the most recent developments and highlight the importance of searching out common circuitry defects underlying compulsive–repetitive behaviors.

► OCD is a prevalent neuropsychiatric disorder. ► Cortico-striatal-thalamo-cortical circuits are central to OCD core features. ► Several recently described genetic mouse models exhibit OCD-like behaviors. ► Genetic mouse models may help researchers identify common circuitry defects in OCD. ► Common circuitry defects may also help to explain key aspects of autism spectrum disorders.