Women showed higher amygdala activity (0.7530 vs. 0.7173, p<0.001) and stronger SNS response to acute stress, while men had greater HPA axis activation (cortisol, p=0.034).
Do healthy men and women exhibit different amygdala and myocardial responses to acute mental stress?
Healthy women exhibit a stronger amygdala and sympathetic nervous system response to acute mental stress compared to men, highlighting sex-specific mechanisms in heart-brain stress responses.
Absolute Event Rate: 0% vs 0%
Abstract Background Despite significant advancements in cardiovascular disease (CVD) management, women continue to experience worse outcomes than men, suggesting the presence of sex-specific mechanisms in cardiovascular risk. Mental stress has emerged as a critical factor influencing CVD, with increased neural activity in the amygdala—a key stress center in the brain—being linked to adverse cardiovascular events. However, little is known about how men and women differ in their heart-brain stress responses. This prospective study aimed to investigate sex differences in amygdala and myocardial responses to acute mental stress, focusing on the role of the hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) activation. Methods Sixty-four healthy volunteers, evenly distributed by sex and aged between 50 and 75 years, were recruited. Participants underwent hybrid positron emission tomography/magnetic resonance (PET/MR) imaging to assess amygdala metabolism using 18FFDG and amygdala perfusion using 13NNH3. Myocardial blood flow (MBF) and flow reserve (MFR) were also measured. Acute stress was induced using the Trier Social Stress Test (TSST) and the Montreal Imaging Stress Task (MIST) while hybrid PET/MR imaging was performed. Additionally, stress-related hormonal and autonomic responses were evaluated by measuring salivary cortisol as an indicator of HPA-axis activation and heart rate response (HRR) as a marker of SNS activation. The primary endpoint of the study was the assessment of sex differences in stress-related neural activity (SNA), quantified as the amygdala-to-cerebellum 18FFDG uptake ratio. Results Women exhibited significantly higher amygdala activity in response to acute mental stress compared to men (0.7530 vs. 0.7173, p0.001), indicating a heightened neural response to stress. Stress-induced amygdala perfusion decreased significantly in women (Δ=-0.0181, p0.001), while the reduction in men was smaller and did not reach statistical significance (Δ=-0.0086, p=0.064). Women demonstrated a higher resting myocardial blood flow (p=0.019), but there was no significant difference in myocardial flow reserve between sexes (p=0.537). Men exhibited a significant increase in cortisol levels following stress exposure (p=0.034), suggesting greater activation of the HPA axis, whereas women had a more pronounced HRR (p=0.049), indicating a stronger SNS response. Conclusion The findings of this study reveal distinct sex differences in the heart-brain stress response. Healthy women exhibit a stronger amygdala response to acute mental stress and predominantly activate the SNS, while men engage the HPA axis more substantially. These differences in neural and cardiovascular stress responses highlight the need for sex-specific approaches in cardiovascular risk assessment and interventions aimed at mitigating the impact of psychological stress on heart health.
Rossi et al. (Sat,) reported a other. Women showed higher amygdala activity (0.7530 vs. 0.7173, p<0.001) and stronger SNS response to acute stress, while men had greater HPA axis activation (cortisol, p=0.034).