Neurobiology of Obsessive-Compulsive Disorder: Serotonin and Beyond

The evidence for the involvement of the serotonergic system in the pathogenesis of obsessive-compulsive disorder (OCD) is circumstantial at best, despite being the focus for most pathophysiological research over the last 2 decades. This hypothesis was initially motivated by the observed differential efficacy of selective serotonin reuptake inhibitors in alleviating OCD symptoms. Direct evidence that serotonergic perturbations are implicated in the pathophysiology of OCD is still sparse. There is growing evidence, from both preclinical and clinical studies, that the dopamine system may also be involved in the pathogenesis of OCD, and that dopaminergic and serotonergic pathways play a role in the genesis and maintenance of obsessive-compulsive symptoms. The complex interactions between both systems, the phenotypic heterogeneity of the disorder, and the limitations of the available tests to probe both systems, make it as yet impossible to draw firm conclusions as to how these systems are implicated. Further studies with more selective pharmacologic agents and neurocognitive probes in humans, studies using deep brain stimulation in combination with neuroimaging, and the development of better animal models for OCD may further our understanding of this disabling condition.