Sex-dependent neural effect of oxytocin during subliminal processing of negative emotion faces

&NA; In line with animal models indicating sexually dimorphic effects of oxytocin (OXT) on social‐emotional processing, a growing number of OXT‐administration studies in humans have also reported sex‐dependent effects during social information processing. To explore whether sex‐dependent effects already occur during early, subliminal, processing stages the present pharmacological fMRI‐study combined the intranasal‐application of either OXT or placebo (n = 86–43 males) with a backward‐masking emotional face paradigm. Results showed that while OXT suppressed inferior frontal gyrus, dorsal anterior cingulate and anterior insula responses to threatening face stimuli in men it increased them in women. In women increased anterior cingulate reactivity during subliminal threat processing was also positively associated with trait anxiety. On the network level, sex‐dependent effects were observed on amygdala, anterior cingulate and inferior frontal gyrus functional connectivity that were mainly driven by reduced coupling in women following OXT. Our findings demonstrate that OXT produces sex‐dependent effects even at the early stages of social‐emotional processing, and suggest that while it attenuates neural responses to threatening social stimuli in men it increases them in women. Thus in a therapeutic context OXT may potentially produce different effects on anxiety disorders in men and women. HighlightsOxytocin (OXT) induced sex‐dependent effect on BOLD level and functional connectivity.OXT decreased neural responses to negative faces in men but increased them in women.Increased ACC activity after OXT was positively linked with trait anxiety in women.OXT decreased functional connectivity in women.Sex might be an important factor moderating the putative anxiolytic effects of OXT.

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