Neuroimaging of Obsessive-Compulsive Disorder: Insights into Serotonergic Mechanisms

The neurobiology of obsessive-compulsive disorder (OCD) is not well understood. The clinical benefits of selective serotonin-reuptake inhibitors (SSRIs) have implicated serotonin, but a clear understanding of its role in symptom onset, aggravation, and resolution remains elusive. Some progress has come from studies using positron emission tomography (PET). PET studies with α-[11C]methyl-l-tryptophan suggest that OCD patients, relative to healthy controls, have elevated brain serotonin synthesis capacity. This increase becomes greater following treatment with either cognitive behavior therapy or an SSRI. A similar phenomenon has been observed in most PET studies targeting the serotonin transporter. Compared to healthy controls, OCD patients commonly exhibit decreased serotonin reuptake potential, a group difference that can also enlarge following treatment. Some of these serotonergic alterations might be unique to OCD. Finally, contrasting with what is seen in those with OCD, brain serotonin synthesis capacity is decreased in people who have difficulty regulating impulsive behaviors, such as those with borderline personality disorder and a history of suicide attempts. Together, these observations raise the possibility that elevated serotonergic tone may be an attempt to inhibit OCD symptoms, a mechanism of “braking” or “resistance” that becomes more effective with treatment.