Sex differences in neural stress responses and correlation with subjective stress and stress regulation

Emotional stress responses, encompassing both stress reactivity and regulation, have been shown to differ between men and women, but the neural networks supporting these processes remain unclear. The current study used functional neuroimaging (fMRI) to investigate sex differences in neural responses during stress and the sex-specific relationships between these responses and emotional stress responses for men and women. A significant sex by condition interaction revealed that men showed greater stress responses in prefrontal cortex (PFC) regions, whereas women had stronger responses in limbic/striatal regions. Although men and women did not significantly differ in emotional stress reactivity or subjective reports of stress regulation, these responses were associated with distinct neural networks. Higher dorsomedial PFC responses were associated with lower stress reactivity in men, but higher stress reactivity in women. In contrast, while higher ventromedial PFC stress responses were associated with worse stress regulation in men (but better regulation in women), dynamic increases in vmPFC responses during stress were associated with lower stress reactivity in men. Finally, stress-induced hippocampal responses were more adaptive for women: for men, high and dynamically increasing responses in left hippocampus were associated with high stress reactivity, and dynamic increases in the left (but not right) hippocampus were associated with worse stress regulation. Together, these results reveal that men and women engage distinct neural networks during stress, and sex-specific neural stress responses facilitate optimal emotional stress responses. Keywords: Stress, Sex, Emotion, fMRI, Medial prefrontal cortex, Hippocampus