Mechanisms Linking Depression to Cardiovascular Risk

BACKGROUND: Multiple studies have demonstrated a higher risk of cardiovascular disease and worse cardiovascular disease (CVD) prognosis associated with depression that appear to synergistically and significantly adversely impact health. Because these initial studies are observational, much work remains to understand this area. If these conditions are mechanistically inter-related, identification of both conditions in the same subject may provide a means of enhancing risk stratification and most appropriately targeting therapy. If the interaction between the conditions is causal not simply associative, appropriate therapy interventions can be designed and tested. DESIGN NARRATIVE: The project is designed to clarify the role of depression on CVD risk by using a co-twin study design. The study will examine twin pairs from the Vietnam Era Twin Registry (VET). Twin pairs will be invited to participate if they meet two criteria: (1) neither has a history of CVD as of 1990 and (2) one twin is diagnosed with depression as of 1992. The study investigates the effects of depression on two indicators of "early" CVD: coronary flow reserve, assessed by means of Positron Emission Tomography (PET) myocardial infusion imaging; and heart rate variability (HRV) assessed by ambulatory electrocardiographic monitoring. It is hypothesized that within each pair, the twins who have clinical depression will exhibit lower coronary vascular reserve and lower heart rate variability compared with their co-twins without a history of depression. Moreover, by comparing the size of the intra-pair difference in these parameters between depression discordant monozygotic and dizygotic twins an estimate of the relative contributions of gene and environmental factors can be ascertained. In addition to the PET and HRV assessments, subjects will complete the Statistical Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV SCID) to document a history of depression, a psychometric battery including the Early Trauma Inventory and Hamilton Depression Scale, and such risk factors as cigarette smoking, physical activity, blood pressure and blood lipids, glucose and insulin, indices of inflammation and thrombogenicity including levels of reactive protein C, fibrinogen, and P-selectin, and neurohormones such as adrenocorticotropic hormone, cortisol, and dehydroepiandrosterone sulphate.

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