Sex differences in neural stress responses over psychosocial stress exposure

Sex differences in stress-induced biobehavioral response and the sex-dependent effects of psychosocial stress on the vulnerability of stress-related psychiatric disorders have been well-acknowledged; however, sex differences in neural stress reactivity have not been sufficiently evaluated. The Montreal Imaging Stress Task was administered to 234 healthy controls (105 males, 129 females) during functional magnetic resonance imaging scanning to detect the effects of psychosocial stress on neural responses. Voxel-wise repeated-measures analysis of variance with stress exposure time as a within-subject variable was performed to detect sex differences in overall brain activation/functional connectivity and in dynamical neural changes during stress exposure when processing psychosocial stress. The males exhibited higher neural stress responses in the insula, inferior parietal lobule, dorsolateral prefrontal cortex, medial prefrontal cortex, and precuneus, and a stronger increase (stress vs. control) in the anti-correlation between amygdala/nucleus accumbens /hippocampus and cortex compared to the females. Additionally, the females exhibited increased deactivation (stress vs. control) in the amygdala, striatum, and medial orbitofrontal cortex (mOFC) during stress exposure, whereas the males did not show this neural dynamic pattern in these brain regions during stress exposure. Our findings highlight sex differences in neural stress responses, particularly in overall brain activation across several key regions involved in core brain networks, and in dynamic changes in limbic/striatal/mOFC regions during stress exposure.