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

Abstract

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: Emotion; Hippocampus; Medial prefrontal cortex; Sex; Stress; fMRI.

Fig. 1

Emotional stress responses from male and female participants. (a) Stress reactivity, as measured by subjective stress ratings to neutral and stressful images throughout exposure (left) and over time (right). Baseline = response to gray screen. (b) Stress regulation skills as assessed by DERS questionnaire. Higher values = greater difficulties. **p < .01; ***p < .001. DERS = Difficulties in Emotion Regulation Scale. Error bars = ± 1 SE.

Fig. 2

Responses to sustained stressor exposure: general and sex-specific. (a) Regions showing overall main effect of Condition (Stress vs Neutral). (b) Regions showing significant Condition (Stress vs Neutral) by Sex (Female vs Male) interaction. (c) Mean BOLD responses for male and female participants within clusters shown in (b) in each condition. Error bars = ± 1 SE. Conditions: Neut = Neutral, Str = Stress. Regions: ACC = anterior cingulate cortex; IFG = inferior frontal gyrus; vmPFC = ventromedial prefrontal cortex; sgACC = subgenual anterior cingulate cortex; dmPFC = dorsomedial prefrontal cortex. All brain images thresholded at voxelwise p < .01, cluster-corrected α = 0.05.

Fig. 3

Sex-specific neural stress responses are differentially associated with emotional stress reactivity for males and females. Numbers indicate Pearson's r values for male and female participants separately. (a) Responses in dmPFC and hippocampus throughout sustained stress exposure differentially predict stress reactivity: higher dmPFC responses were associated with greater subjective stress for females and lower stress for males, whereas higher hippocampal responses had the opposite pattern. Mean BOLD responses were computed as the average response to the Stress condition (6 blocks) – Baseline (2 Gray blocks). (b) Changes in ventromedial PFC response (subgenual anterior cingulate, sgACC) throughout stress exposure were associated with changes in subjective stress, with increasing responses associated with decreasing subjective stress for males but increasing subjective stress for females. Changes in left hippocampal responses showed the opposite pattern. Change in BOLD was computed as the difference between Late (last 2 Stress blocks) – Early (first 2 Stress blocks), each relative to Baseline. dmPFC = dorsomedial prefrontal cortex; hipp = hippocampus. Regions shown in Fig. 2b. *p < .05.

Fig. 4

Sex-specific neural stress responses are differentially associated with stress regulation for males and females. Numbers indicate Pearson's r values for male and female participants separately. (a) Responses in vmPFC (ventromedial prefrontal cortex) regions throughout stress differentially predict DERS scores, with higher responses correlating with worse emotion regulation for males and better emotion regulation for females. This pattern was significant for the Difficulties Engaging in Goal-Directed Behavior, Nonacceptance of Emotional Responses, and Impulse Control Difficulties subscales. As in Fig. 3, BOLD responses were computed as the average response to the Stress condition (6 blocks) – Baseline. (b) Changes in hippocampal BOLD throughout stress were differentially associated with DERS for left and right regions. Increasing responses in left hippocampus correlated with worse emotion regulation for males and better emotion regulation for females, whereas increasing responses in right hippocampus correlated with better regulation for males and worse regulation for females. This pattern was significant for the Lack of Emotional Awareness subscales. As in Fig. 3, change in BOLD responses was computed as Late (last 2 blocks) – Early (first 2 blocks) of stress exposure, each relative to Baseline . *p < .05, **p < .01.