Impaired P50 suppression in fear extinction in obsessive-compulsive disorder

Abstract

The processes of fear conditioning and extinction are thought to be related to the pathophysiology of anxiety disorders including obsessive-compulsive disorder (OCD). We have reported alterations of auditory P50 suppression in human fear conditioning and extinction in healthy control subjects (Kurayama et al., 2009). In the study, P50 suppression was impaired transiently in the course of fear acquisition and extinction. In this study, we investigated the changes of P50 suppression with OCD patients in the course of the same experimental paradigm. 39 patients with OCD and 21 healthy control subjects were recruited. In the acquisition phase of classical fear conditioning, 10 pairings of the conditioned stimulus (CS; the visual stimulus from a light-emitting diode) and the unconditioned stimulus (US; the electrical stimulus to the wrist) were administered, and in the extinction phase, 10 CS without US were administered. P50 auditory evoked potentials were measured as the first stimulus sound (S1) and the second stimulus sound (S2) in double-click paradigm with a 500 ms interval. P50 S2/S1 ratio was used to evaluate P50 suppression. The mean P50 S2/S1 ratio in patients with OCD significantly elevated from baseline level during the fear acquisition as that in healthy controls, but the elevated S2/S1 ratio did not recover to baseline level. The S2/S1 ratio in the extinction phase was significantly higher in the OCD patient group than in the healthy control group. In conclusion, our data suggested that P50 sensory gating in fear extinction was impaired in patients with OCD.