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.
Highlights
Deficits in social functioning are core features of psychosis and predictive for the onset, development, course and outcome of this illness[1]
The first main finding is that OT did not affect brain responses during belief inference but reduced activation in the bilateral inferior frontal gyrus during social emotion inference
The second main finding is that neural activation in the left inferior frontal gyrus during social emotion inference after OT administration was modulated by baseline social-emotional abilities, which moderated the relationship between brain activation and task performance
Summary
Deficits in social functioning are core features of psychosis and predictive for the onset, development, course and outcome of this illness[1]. Mind-reading, i.e., the ability to infer others’ mental states, is integral for social interactions[7] and impaired in early psychosis patients[8] and CHR-P subjects[9,10]. While the bilateral anterior insula/inferior frontal gyrus is activated during emotional empathy, activation in the left midcingulate cortex and left anterior insula is more related to the cognitive aspect of empathy[13]. Previous functional magnetic resonance imaging (fMRI) studies in CHR-P individuals reported increased activation in the prefrontal cortex including the inferior frontal gyrus, posterior cingulate cortex and the temporoparietal cortex during inferring others’ mental status relative to healthy controls, suggesting a compensatory overactivation of brain regions critical for empathic responses during mental state attribution[14,15]. Another study observed reduced bilateral inferior frontal gyrus activation during inferring others’ emotions but not beliefs in CHR-P subjects relative to healthy subjects[16]
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