Oral Oxytocin Blurs Sex Differences in Amygdala Responses to Emotional Scenes

BACKGROUND: Sex differences are shaped both by innate biological differences and the social environment and are frequently observed in human emotional neural responses. Oral administration of oxytocin (OXT), as an alternative and noninvasive intake method, has been shown to produce sex-dependent effects on emotional face processing. However, it is unclear whether oral OXT produces similar sex-dependent effects on processing continuous emotional scenes. METHODS: The current randomized, double-blind, placebo-controlled neuropsychopharmacological functional magnetic resonance imaging experiment was conducted in 147 healthy participants (OXT = 74, men/women = 37/ 37; placebo = 73, men/women = 36/37) to examine the oral OXT effect on plasma OXT concentrations and neural response to emotional scenes in both sexes. RESULTS: At the neuroendocrine level, women showed lower endogenous OXT concentrations than men, but oral OXT increased OXT concentrations equally in both sexes. Regarding neural activity, emotional scenes evoked opposite valence-independent effects on right amygdala activation (women > men) and its functional connectivity with the insula (men > women) in men and women in the placebo group. This sex difference was either attenuated (amygdala response) or even completely eliminated (amygdala-insula functional connectivity) in the OXT group. Multivariate pattern analysis confirmed these findings by developing an accurate sex-predictive neural pattern that included the amygdala and the insula under the placebo but not the OXT condition. CONCLUSIONS: The results of the current study suggest a pronounced sex difference in neural responses to emotional scenes that was eliminated by oral OXT, with OXT having opposite modulatory effects in men and women. This may reflect oral OXT enhancing emotional regulation to continuous emotional stimuli in both sexes by facilitating appropriate changes in sex-specific amygdala-insula circuitry.