Toward a Neurodevelopmental Model of Obsessive–Compulsive Disorder

Background: Neurobiological models for obsessive–compulsive disorder (OCD) have consistently implicated ventral prefrontal cortical and striatal circuits in the pathophysiology of this disorder, but typically have not utilized a developmental framework for conceptualizing the illness. Methods: We describe an integrated series of neurobiologic studies aimed at testing the hypothesis that neurodevelopmental abnormalities of ventral prefrontal–striatal circuits may be involved in and contribute to the etiology and presentation of the illness. Results: Using studies of oculomotor physiology, we have identified a selective deficit in neurobehavioral response suppression in OCD that may be related to failures in the developmental maturation of frontostriatal circuitry. Magnetic resonance imaging studies showed that treatment-naive pediatric OCD patients had significant volumetric abnormalities in ventral prefrontal cortical and striatal regions but no abnormalities in dorsolateral prefrontal cortex. Severity of OCD symptoms but not illness duration was related to ventral prefrontal cortical and striatal volumes. Conclusions: Critical neurodevelopmental changes in ventral prefrontal–striatal circuitry may be associated with the initial presentation of OCD, and a developmentally mediated network dysplasia may underlie OCD. Such dysplasia in ventral prefrontal cortical circuits could manifest clinically by disrupting brain functions that mediate ongoing purposive behaviors.