Sex differences in brain activation patterns with mental stress in patients with coronary artery disease

Background: Stress is an important contributor to myocardial ischemia and the progression of coronary artery disease (CAD), and women are more susceptible than men to these effects. Little is known, however, about the neural basis of these sex differences. Methods: We investigated sex differences in neural correlates of mental stress in a sample of 53 female and 112 male participants (N = 165) with CAD, with and without mental stress-induced myocardial ischemia (MSI), during exposure to mental arithmetic tasks and public speaking stress tasks using high-resolution positron emission tomography (HR-PET) and radiolabeled water imaging of the brain. Results: Women compared to men had significantly greater activation with stress in the right frontal (BA 9, 44), right parietal lobe (Area 3, 6, 40), right posterior cingulate gyrus (BA 31), bilateral cerebellum, and left temporal/fusiform gyrus (BA 37) and greater deactivation in bilateral anterior cingulate gyrus (BA 24, 32), bilateral medial frontal gyrus (BA 6, 8, 9, 10), right parahippocampal gyrus, and right middle temporal gyrus (BA 21). Women with MSI (but not those without MSI) showed significantly greater activation than men in the right posterior cingulate gyrus (BA 31) and greater deactivation in several frontal and temporal lobe areas. Conclusion: Men and women with CAD show differences in responses to stress in brain limbic areas that regulate emotion, and these functional responses differ by MSI status. Our results suggest that the cingulate gyrus may be involved in sex differences in MSI.