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Depression and Coronary Artery Atherosclerosis and Reactivity in Female Cynomolgus Monkeys

From Wake Forest University School of Medicine (C.A.S., J.K.W.), Winston–Salem, NC; and Medical University of South Carolina (K.L.-L., R.F.A.), Charleston, SC.

Address reprint requests to: Carol A. Shively, Department of Pathology (Comparative Medicine), Wake Forest University School of Medicine, Medical Center Boulevard, Winston–Salem, NC 27157-1040. Email cshively{at}wfubmc.edu

OBJECTIVE: Depression and coronary heart disease (CHD) are comorbid conditions, and it is thought that depression may increase the risk of CHD. However, the evidence for the latter relationship is sparse and difficult to collect. Cynomolgus monkeys (Macaca fascicularis) have been used effectively as animal models of CHD risk and depression. Here we report the results of a comparison of physiological characteristics, coronary artery reactivity, and atherosclerosis in 16 depressed and 26 nondepressed female cynomolgus monkeys.

METHODS: Forty-two females were housed in single cages for 3 months and in their final social groups for 26 months, during which time they consumed an atherogenic diet.

RESULTS: During the 26-month social grouping period, 16 of the females displayed behavioral depression, defined as a slumped or collapsed body posture accompanied by a relative lack of responsiveness to environmental stimuli. These depressed monkeys had higher heart rates throughout the study, even during the single-caging period, suggesting a priori differences in the autonomic function of females that displayed behavioral depression relative to those that did not. Hypothalamic-pituitary-adrenal function was impaired in all females during the single-caging period and during new group formation. By 26 months in the final social groups, females that never displayed depression were more sensitive to glucocorticoid negative feedback in a dexamethasone suppression test than females that displayed behavioral depression. Depressed females had poorer quality ovarian function than their nondepressed counterparts. There was no difference between depressed and nondepressed females in coronary artery atherosclerosis extent or cineangiographically determined coronary vasomotor responses to infused vasoactive substances (vascular reactivity).

CONCLUSION: Depression did not appear to be associated with CHD risk in these female monkeys.

Key Words: CHD, • depression, • females, • monkey, • cortisol, • heart rate.

Abbreviations: CAA = coronary artery atherosclerosis;; CHD = coronary heart disease;; DST = dexamethasone suppression tests;; HPA = hypothalamic-pituitary-adrenal;; HR = heart rate;; MI = myocardial infarction.

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