Deep Brain Stimulation Induces Striatal Dopamine Release in Obsessive-Compulsive Disorder

Background: Obsessive-compulsive disorder is a chronic psychiatric disorder related to dysfunctional dopaminergic neurotransmission. Deep brain stimulation (DBS) targeted at the nucleus accumbens (NAc) has recently become an effective treatment for therapy-refractory obsessive-compulsive disorder, but its effect on dopaminergic transmission is unknown. Methods: We measured the effects of NAc DBS in 15 patients on the dopamine D-2/3 receptor availability in the striatum with [I-123] iodobenzamide ([I-123] IBZM) single photon emission computed tomography. We correlated changes in [I-123] IBZM binding potential (BP) with plasma levels of homovanillic acid (HVA) and clinical symptoms. Results: Acute (1-hour) and chronic (1-year) DBS decreased striatal [I-123] IBZM BP compared with the nonstimulated condition in the putamen. BP decreases were observed after 1 hour of stimulation, and chronic stimulation was related to concurrent HVA plasma elevations, implying DBS-induced dopamine release. BP decreases in the area directly surrounding the electrodes were significantly correlated with changes in clinical symptoms (45% symptom decrease). Conclusions: NAc DBS induced striatal dopamine release, which was associated with increased HVA plasma levels and improved clinical symptoms, suggesting that DBS may compensate for a defective dopaminergic system.