The relationship between executive function impairment and serotonergic sensitivity in obsessive-compulsive disorder

While studies of obsessive-compulsive disorder (OCD) have demonstrated both neuropsychological and serotonergic (5-HT) dysfunction, none have integrated these two spheres. We report concomitant abnormalities in both areas that may impact on the pathophysiology and treatment of OCD. We utilized Trail-making B-A, a neuropsychological test of cognitive set-switching, to highlight executive function abnormalities in OCD patients (N = 50) and normal controls (N = 31). OCD patients were found to be significantly impaired on Trails B-A. Prolactin response to double-blind, single-dose meta-chlorophenyl piperazine (m-CPP) and placebo served as a measure of 5-HT sensitivity, OCD patients (N = 42) had a blunted prolactin response to m-CPP, in contrast to normal controls (N = 15; F = 2.462; df = 3.62; p = 0.06). Of interest, the peak delta-prolactin response to m-CPP significantly negatively correlated with frontal lobe set-switching impairment in OCD patients (r = 0.37, n = 26, p = 0.03) but not in normal controls. This suggested that OCD patients with greater frontal lobe impairment had concomitantly more substantial serotonergic dysfunction.