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

Abstract

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 Mu-suppression 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.

Conflict of interest statement

Dr. Marder has served as a consultant to Roche, Allergan, Takeda, Neurocrine, Newron, Boeringer-Ingelheim, Otsuka, Acadia, Lundbeck, and Teva. He has received research support from Neurocrine and Takeda. Dr. Green has been a consultant to AiCure, Lundbeck, and Takeda, and he is on the scientific board of Cadent. He has received research funds from FORUM. The remaining authors declare no competing interests.

Figures

Fig. 1

CONSORT flow chart for enrollment, allocation, and analysis of data

Fig. 2

Mean log10 Mu suppression for placebo administration only. Error bars represent ±1 standard error. Mean values for the emotion identification (black), gender identification (gray), and intention identification condition (light gray) are all significantly different from zero, indicating significant mu suppression occurred

Fig. 3

Log10 Mu suppression values for each observation for emotion identification (black circle), gender identification (gray triangle), and intention identification (light gray square) are shown for placebo (IU = 0) and the eight OT IU doses. Mean values for each dose are displayed as overlaid lines following the same color scheme. A reference line for the mean of the placebo condition (horizontal black line), along with lines for the 95% confidence interval (dashed black lines above and below mean), is shown

Fig. 4

Pupil responses to the facial affect identification task. Tracings are shown for responses to fearful (thin solid line), happy (large dashed line), neutral (small dashed line), and scrambled (thick solid line) faces