Lifetime History of Depression, Type 2 Diabetes, and Endothelial Reactivity to Acute Stress in Postmenopausal Women

Coronary heart disease is a major cause of mortality in women and persons with diabetes. Mental stress and major depressive disorder have both been associated with coronary heart disease. Endothelial functioning is a clinically meaningful manifestation of CHD that is detectable in its earliest stages. This study aims to determine whether acute stress and lifetime history of major depressive disorder are associated with functional and biochemical markers of endothelial function and whether this relationship varies by diabetes status. Resting endothelial function was assessed for n = 215 postmenopausal women with no known or suspected coronary artery disease participated. Of these, 108 had a positive lifetime major depressive disorder (L-MDD; assessed through structured clinical interview) and had been free of major depressive disorder for > 6 months; 103 had type 2 diabetes. Endothelial reactivity to acute mental stress was assessed for n = 114 of the participants. Endothelial function was assessed by flow-mediated dilation of the brachial artery (FMD) by total plasma nitrite, the cumulative molecule from nitric oxide (NO) generation, and by plasma endothelin-1 (ET-1). Participants with L-MDD had lower NO and lower FMD compared to never-depressed controls. Secondary analyses suggest that among participants with L-MDD, antidepressant medications are associated with higher NO. Participants with diabetes had higher NO but lower FMD than nondiabetic controls. Mental stress affected FMD in the entire sample. Diabetes moderated the effect of mental stress on NO and L-MDD moderated the effect of mental stress on ET-1. History of depression, even in full remission, is associated with impaired endothelial functioning regardless of diabetes status. Acute mental alters FMD, NO, and ET-1 differentially among subgroups.