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Viola Vaccarino, MD, PhD; John Votaw, PhD; Tracy Faber, PhD; Emir Veledar, PhD; Nancy V. Murrah, RN; Linda R. Jones, BS; Jinying Zhao, MD, PhD; Shaoyong Su, PhD; Jack Goldberg, PhD; J. Paolo Raggi, MD; Arshed A. Quyyumi, MD; David S. Sheps, MD; J. Douglas Bremner, MD

Arch Intern Med. 2009;169(18):1668-1676.

Background  Major depressive disorder (MDD) is associated with coronary heart disease (CHD), but the mechanisms are unclear. The presence of MDD may increase CHD risk by affecting microvascular circulation. It is also plausible that genetic factors influencing MDD may overlap with those for CHD. We sought to examine the relationship between MDD and coronary flow reserve (CFR), the ratio of maximum flow during stress to flow at rest measured in milliliters per minute per gram of tissue.

Methods  We examined 289 male middle-aged twins, including 106 twins (53 twin pairs) discordant for a lifetime history of MDD and 183 control twins (unrelated to any twins in the experimental group) without MDD. To calculate CFR, we used positron emission tomography with nitrogen 13 (¹³N) ammonia to evaluate myocardial blood flow at rest and after adenosine stress. A standard perfusion defect score was also used to assess myocardial ischemia.

Results  There was no difference in myocardial ischemia between twins with and without MDD. Among the dizygotic twin pairs discordant for MDD, the CFR was 14% lower in the twins with MDD than in their brothers without MDD (2.36 vs 2.74) (P = .03). This association was not present in the monozygotic discordant pairs who were genetically matched (2.86 vs 2.64) (P = .19). The zygosity-MDD interaction after adjustment was significant (P = .006). The CFR in the dizygotic twins with MDD was also lower than in the control twins.

Conclusions  Our results provide evidence for a shared genetic pathway between MDD and microvascular dysfunction. Common pathophysiologic processes may link MDD and early atherosclerosis.

Author Affiliations: Department of Medicine, Division of Cardiology (Drs Vaccarino, Veledar, Zhao, Su, Raggi, Quyyumi, Sheps, and Bremner and Mss Murrah and Jones), and the Departments of Radiology (Drs Votaw and Faber) and Psychiatry and Behavioral Sciences (Dr Bremner), Emory University School of Medicine, Atlanta, Georgia; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta (Dr Vaccarino); and the Vietnam Era Twin Registry and the University of Washington School of Public Health and Community Medicine, Seattle (Dr Goldberg). Dr Zhao is currently with the Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City.

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