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Depressive Symptoms and Heart Rate Variability: Evidence for a Shared Genetic Substrate in a Study of Twins

From the Division of Cardiology (V.V., S.S., C.M., N.V.M., L.J.), Department of Medicine, and the Department of Psychiatry and Behavioral Sciences (J.D.B., F.J.), Emory University School of Medicine, Atlanta, Georgia; Division of Cardiovascular Medicine (RL, FL), Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; Department of Epidemiology (V.V.), Rollins School of Public Health, Emory University, Atlanta, Georgia; and The Vietnam Era Twin Registry (J.G.), Seattle, Washington.

Address correspondence and reprint requests to Viola Vaccarino, Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1256 Briarcliff Road NE, Suite-1 North, Atlanta, GA 30306. E-mail: viola.vaccarino{at}emory.edu

Objective: To clarify the relationship between depression and heart rate variability (HRV) in a sample of twins. Reduced HRV, a measure of autonomic dysfunction, has been linked to depression but many studies have inadequately controlled for familial and environmental factors. Furthermore, little is known about whether depression and HRV share common genetic pathways.

Methods: We performed power spectral analysis on 24-hour ambulatory electrocardiograms in 288 middle-aged male twins. Log-normalized ultra low, very low, low, high frequency, and total power were calculated. A lifetime history of major depressive disorder (MDD) was determined, using the Structured Clinical Interview for Psychiatry Disorders, and current depressive symptoms were measured with the Beck Depression Inventory. Mixed-effect regression models were used to account for intrapair variability and estimate within-pair effects at the same time controlling for potential confounders.

Results: Both current depressive symptoms and a history of MDD were significantly associated with lower HRV. There was a graded effect, and power in each frequency band was 29% to 36% lower in the lowest band compared with the highest BDI category. All HRV measures except high frequency remained significantly associated with current depressive symptoms in multivariable analysis, but not with lifetime history of MDD. When analyses were stratified by zygosity, a significant within-pair association between BDI score and HRV was found in the dizygotic but not in the monozygotic twins, suggesting a genetic influence on the association.

Conclusions: A shared, genetically influenced biological pathway underlies the association between depression and lower HRV. These two phenotypes may be the expression of a generalized neurobiological perturbation.

Key Words: autonomic function • electrophysiology • genetic factors • psychosocial factors • risk factors

Abbreviations: BDI = Beck Depression Inventory; CAD = coronary artery disease; DZ = dizygotic; HRV = heart rate variability; MDD = major depressive disorder; MZ = monozygotic; PTSD = posttraumatic stress disorder.

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