Project Summary

Christian Otte, M.D. (Young Investigator 2005) of the University of Hamburg, plans to study the relationship among polymorphisms in the gene for the serotonin transporter (5-HTT) and depression, cardiovascular disease and changes in cortisol and norepinephrine, two neurotransmitters associated with depression. Depression increases the likelihood of adverse outcomes for people with coronary heart disease (CHD), but the how depression affects cardiovascular outcomes are not known. Recent studies suggest that a functional polymorphism of the serotonin transporter gene (5-HTT) is associated with the development of depression, and may be involved in cardiovascular disease. Also, animal studies have shown that the 5-HTT is involved in the regulation of cortisol and norepinephrine, both of which are associated with depression. To further study these relationships, Dr. Otte plans to characterize the 5-HTTpolymorphism in people who have participated in the Heart and Soul Study, a large and well-characterized sample of 1,024 subjects with CHD who were recruited between 9/00-12/02, and are being followed for 2 years to determine the mechanisms of association between depression and CHD events. At baseline (9/00-12/02), all study participants completed a diagnostic interview for depression, gave a blood sample for DNA testing, and collected 24-hour urine for measurement of norepinephrine and cortisol. The large size of this cohort is suited for a genetic association study. The proposed study will enhance understanding of the risk factors for depression in heart disease and the mechanisms by which depression leads to worse cardiac outcomes.

Program Area: MOOD DISORDERS\Unipolar Depression\Cardiovascular Disease

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