OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding

Abstract Obsessive-compulsive disorder (OCD) is characterized by impaired sensorimotor gating, as measured using prepulse inhibition(PPI). This effect may be related to abnormalities in the serotonin (5-HT) system. 5-HT 1B agonists can impair PPI, produce OCD-like behaviors in animals, and exacerbate OCD symptoms in humans. We measured 5-HT 1B receptor availability using 11 C-P943 positron emission tomography (PET) in unmedicated, non-depressed OCD patients ( n =12) and matched healthy controls (HC; n =12). Usable PPI data were obtained from 20 of these subjects (10 from each group). There were no significant main effects of OCD diagnosis on 5-HT 1B receptor availability ( 11 C-P943 BP ND ); however, the relationship between PPI and 11 C-P943 BP ND differed dramatically and significantly between groups. 5-HT 1B receptor availability in the basal ganglia and thalamus correlated positively with PPI in controls; these correlations were lost or even reversed in the OCD group. In cortical regions there were no significant correlations with PPI in controls, but widespread positive correlations in OCD patients. Positive correlations between 5-HT 1B receptor availability and PPI were consistent across diagnostic groups only in two structures, the orbitofrontal cortexand the amygdala. Differential associationsof 5-HT 1B receptor availability with PPI in patients suggest functionally important alterations in the serotonergic regulation of cortical/subcortical balance in OCD.