Acute oxytocin effects in inferring others' beliefs and social emotions in people at clinical high risk for psychosis

Abstract

Social deficits are key hallmarks of the Clinical High Risk for Psychosis (CHR-P) state and of established psychotic disorders, and contribute to impaired social functioning, indicating a potential target for interventions. However, current treatments do not significantly ameliorate social impairments in CHR-P individuals. Given its critical role in social behaviour and cognition, the oxytocinergic (OT) system is a promising target for novel interventions in CHR-P subjects. In a double-blind, placebo-controlled, crossover design, 30 CHR-P males were studied using functional magnetic resonance imaging (fMRI) on two occasions, once after 40IU self-administered intranasal OT and once after placebo. A modified version of the Sally-Anne task was used to assess brain activation during inferring others' beliefs and social emotions. The Reading the Mind in the Eyes Test was acquired prior to the first scan to test whether OT effects were moderated by baseline social-emotional abilities. OT did not modulate behavioural performances but reduced activation in the bilateral inferior frontal gyrus compared with placebo while inferring others' social emotions. Furthermore, the relationship between brain activation and task performance after OT administration was moderated by baseline social-emotional abilities. While task accuracy during inferring others' social emotion increased with decreasing activation in the left inferior frontal gyrus in CHR-P individuals with low social-emotional abilities, there was no such relationship in CHR-P individuals with high social-emotional abilities. Our findings may suggest that acute OT administration enhances neural efficiency in the inferior frontal gyrus during inferring others' social emotions in those CHR-P subjects with low baseline social-emotional abilities.

Fig. 1. Task design.

a Each story consisted of four frames with two people. There are 10 different types of stories (see supplementary Fig. 1). b Each story was presented three times consecutively per each run. At the end of each story presentation, participants were asked to answer the following three types of questions that asked emotion of the character, belief of the character, and fact (control condition). These three questions appeared in a pseudorandom order, followed by an answer frame. c Trial timing. 3.5 s story presentation with four frames of a black and white comic. Then, a frame with a question written in white letters on the black screen was shown for 2 s. After 2.5–3.5 s white fixation cross on the black screen, another frame was presented to illustrate an arrow and a star to help to answer the question (3 s). At the end of one story, a 3-s fixation cross was shown. During the last frame and fixation cross, participants were instructed to answer the question with yes or no.

Fig. 2. Behavioral task performance.

Accuracies and reaction times in response to correct responses for both treatments during the task.

Fig. 3. Imaging results.

a Significant reduced activation in the left and right inferior frontal gyrus (IFG) during inferring others’ social emotion (social emotion > control) after OT compared with the placebo administration. Images are displayed at a cluster-forming threshold of p<0.001 uncorrected, with an extent threshold of 20 voxels. Colour bars indicate t values. b Significant correlation between left IFG activation after OT administration (i.e. parameter estimate, PE) during inferring others’ social emotion and baseline RMET performance (r=0.388, p=0.046). c Moderator effect of baseline RMET performance on the relationship between left IFG activation after OT administration (i.e. parameter estimate, PE) and task accuracy during inferring others’ social emotions after OT administration.