High levels of depression and hopelessness increase risk of cardiovascular disease (CVD) morbidity and mortality. Likewise, CVD prevalence and incidence are inversely related to socioeconomic status (SES). Mechanisms by which depression, hopelessness, and low SES increase risk for CVD are not well understood; however, research shows that traditional coronary risk factors cannot account for much of the observed associations. Several studies indicate that depression and hopelessness are associated with abnormalities in serotonin (5HT) function and dysregulation of the hypothalamic-pituitary-adrenal axis, resulting in excess secretion of cortisol, an important stress hormone. Chronic stress exposure and higher levels of psychological stress associated with living in poor conditions also are thought to adversely influence 5HT and cortisol levels. Both 5HT and cortisol have cardiovascular effects and are involved in pathogenesis of CVD. However, to our knowledge, no prior population-based epidemiologic studies have examined whether serotonergic and glucocorticoid mechanisms mediate the well-documented associations between depression, hopelessness, low SES and atherosclerosis. The proposed study takes advantage of a unique opportunity to test these hypotheses within the context of the Kuopio Ischemic Heart Disease (KIHD) Risk Factor Study, the most comprehensive study of biopsychosocial risk factors for atherosclerosis and related morbidity and mortality ever to be conducted. The KIHD study is conducted in Kuopio, Finland, and has been at the forefront of research into psychosocial determinants of CVD. The proposed study will utilize existing data to examine plasma cortisol concentrations and whole blood 5HT and platelet 5HT receptor and transporter binding in relation to depression, hopelessness, SES and athersclerosis. Participants include a population-based cohort of 800 men and 800 women aged 53-71. The investigators argue that depression, hopelessness, and low SES will be related to decreased levels of 5HT and elevated plasma cortisol; that both 5HT and cortisol will mediate the effects of depression, hopelessness, and low SES on carotid atherosclerosis; that these mediating effects will be evident after taking into account traditional risk factors (although the effects of cortisol also may operate through some of these risk factors); and that 5HT function will be lower in women compared to men. Depression and CVD are expected to be the two leading causes of disability in the next 20-25 years. Moreover, widespread economic disparities and associated health consequences are evident throughout the world. Thus, understanding mechanisms by which psychological states and SES are related to the development and progression of CVD is a critical task and one that will shed light on treatment and prevention strategies for patients with atherosclerotic vascular disease and for patients suffering from depression or hopelessness. Importantly, delineating the mechanisms by which psychosocial attributes influence atherosclerosis also will advance understanding of important mind-body interactions in cardiac disease processes.
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