Depressive behavior and coronary artery atherogenesis in adult female cynomolgus monkeys

Abstract

Objective: To examine depressive behavior and early coronary artery atherogenesis in 36 socially housed female cynomolgus monkeys, an established model of atherogenesis and depression. Coronary heart disease (CHD) is caused by coronary artery atherosclerosis (CAA) and its sequelae which develop over a period of decades. Thus, in prospective studies of depression and CHD, CAA was likely present at baseline in most subjects who experienced cardiac events. Little is known about the relationship between depression and CAA.

Methods: The monkeys were free of atherosclerosis before being fed a diet containing moderate amounts of fat and cholesterol for 52 months. Depressed behavior and activity levels recorded in weekly 15-minute focal samples, telemetered 24-hour heart rate, plasma total (TPC) and high-density lipoprotein cholesterol (HDLC), luteal phase serum progesterone concentrations, basal cortisol, cortisol response to corticotrophin-releasing hormone (CRH), and CAA extent were assessed.

Results: Time spent in depressed behavior over 4 years was significantly associated with early CAA (r = .73, p < .001), as were activity level, 24-hour heart rate, TPC, HDLC, cortisol response to CRH, and mean peak progesterone (all p < or = 0.05). Depressed females had four times the CAA compared with nondepressed females.

Conclusions: Depression in primates is associated with perturbations in multiple CHD risk factors and accelerated early atherogenesis. These data are consistent with the hypotheses that depression and CAA both stem from a common mechanism and that depression may cause CAA.

Figure 1

Experimental design. Social groups were reorganized once at the onset of Phase 2 (Social Reorg). Behavior and ovarian function were assessed throughout the study, and other clinical evaluations were made at the end of each phase as indicated by the arrows.

Figure 2

Monkey displaying depressed (left) or alert (right) behavior.

Figure 3

Linear relationship between a history of depressive behavior and coronary artery atherosclerosis extent.

Figure 4

Magnitude of the differences in coronary artery atherosclerosis extent of less depressed (n = 17) and more depressed (n = 10) females. A t test was used to generate the p value.

Figure 5

Representative examples of atherosclerotic lesion from cross sections of the left anterior descending artery of a nondepressed (left) and depressed (right) monkey. Atherosclerotic lesion was quantified as the area of the intima (IA), i.e., the area internal to the internal elastic lamina (IEL). Sections were stained with Verhoeff van Gieson stain. Lesion area of the nondepressed monkey was minimal (IA = 0.08 mm²), consisting of eccentric fatty streak and small fibro-fatty plaque. The lesion of the depressed monkey was much more extensive (IA = 0.52 mm²), consisting of a moderately advanced concentric fibro-fatty to fibro-muscular plaque with a small focus of calcium. Multifocal destruction of the IEL and media and lipid infiltration into the media were apparent.