A dose-finding study of oxytocin using neurophysiological measures of social processing

Recent interest has focused on oxytocin (OT), a neurotransmitter that promotes social processing, to improve social functioning in people with schizophrenia. However, little information is available regarding the doses of OT that are effective for influencing social processing in the brain (i.e., target engagement). In this study, we conducted a double-blind, placebo-controlled, cross-over dose ranging study of OT. In total 47 patients with schizophrenia were randomly assigned to one of eight doses of OT (8, 12, 24, 36, 48, 60, 72, or 84 IU). Patients completed two social processing tasks: one electroencephalography (EEG) task, a biological motion Musuppression task (i.e., identifying the gender, emotion, or direction of walking of point-light animations of human movement); and one pupillometry task, pupil dilation in response to viewing affective faces. Participants completed these tasks twice, one week apart, and were randomly administered drug or placebo intranasally 30 min prior to each session. Mu-suppression, i.e., suppression of oscillations in the 8-12 Hz range over central electrodes in response to social stimuli, was significantly enhanced at doses of 36 and 48 IU in comparison to placebo, but not at other doses. Significant pupil dilation was observed in response to faces vs. non-face stimuli, though there were no drug effects at any dose. Results suggest that OT affects central measures of social information processing in patients with schizophrenia and is optimal at a mid-range dose (36-48 IU). These results provide dosing guidance for future studies of OT to be used to enhance social processing in people with schizophrenia.