Effects of a mental stress challenge on brain function in coronary artery disease patients with and without depression.

Objective: Coronary artery disease (CAD) patients with comorbid depression show an increase in mortality compared to cardiac patients without depression, but the mechanisms mediating this effect remain obscure. One possible explanation for this finding is that depressed patients with CAD exhibit an increased vulnerability to stress. The purpose of this study was to assess the effects of stress and depression on brain function and to explore its relationship with myocardial ischemia in CAD patients. Methods: Patients with CAD and depression (N = 13) and CAD without depression (N = 15) underwent imaging of the brain with positron emission tomography and [O-15] water and imaging of the heart with single photon emission computed tomography (SPECT) and [Tc-99(m)] sestamibi under mental stress task and control conditions. Results: CAD patients with depression compared to nondepressed showed decreased function with mental stress in the rostral anterior cingulate, the hippocampus, parts of the dorsolateral temporal and parietal cortex, the cerebellum, and the uncus, with increased blood flow in the parahippocampus, visual association cortex, and posterior cingulate. Depressed CAD patients who became ischemic during a mental stress task had relative decreases in the caudal and posterior cingulate, orbitofrontal cortex, and cerebellum, and increased activation in the parietal cortex and precuneus/visual association cortex compared to nonischemic depressed CAD patients. Conclusions: These findings are consistent with dysfunction in a network of brain regions involved in the stress response in patients with comorbid CAD and depression that has direct and indirect links to the heart, suggesting a pathway by which stress and depression could lead to increased risk of heart disease related morbidity and mortality.