The Serotonergic System in Obsessive-Compulsive Disorder

Abstract Obsessive-compulsive disorder (OCD) is a psychiatric disorder consisting of obsessions and compulsions. Over the past two decades it has been suggested that OCD might be related to the functioning of brain serotonin systems, mainly because of the anti-obsessional efficacy of selective serotonin reuptake inhibitors (SSRIs). Though the efficacy of SSRIs suggests a role of the serotonergic system in OCD, the exact function of serotonin (5-HT) is still unclear. Is the serotonergic system implicated in the pathophysiology of OCD, or is it implicated in the treatment effect in OCD? Do SSRIs compensate for a fundamental abnormality of the serotonergic system, or do SSRIs modulate an intact serotonergic system to compensate for another neurotransmitter mechanism? This chapter reviews five lines of evidence that have been cited in support of the 5-HT hypothesis: (1) pharmacotherapy; (2) pharmacologic challenge studies; (3) receptor binding studies; (4) genetic association studies; and (5) animal models.