Atherosclerosis 137 (1998) 259 – 266 Effects of chronic social separation on cardiovascular disease risk factors in female cynomolgus monkeys Sheree L. Watson, Carol A. Shively *, Jay R. Kaplan, Scott W. Line Department of Comparatie Medicine, Wake Forest Uniersity School of Medicine, Medical Center Bld., Winston -Salem, NC 27157 -1040, USA Received 6 November 1996; received in revised form 28 October 1997; accepted 29 October 1997 Abstract A lack of social support is associated with increased risk of coronary heart disease morbidity and mortality in human beings. Similarly, chronic social separation (single cage housing) potentiates atherosclerosis in female monkeys. Under the hypothesis that autonomic arousal and/or ovarian impairment may mediate this effect (as both are associated with increased atherosclerosis), heart rate and luteal phase plasma progesterone concentrations were measured in 12 female cynomolgus monkeys that were first socially housed, then individually housed, and finally returned to their original social groups. Afternoon heart rates increased during social separation compared to the social groupings (P 0.001). Increased heart rates could not be explained by activity levels, which were lower during social separation than in social groupings (P 0.001). Ovarian function (i.e. luteal-phase progesterone concentrations) was not influenced by housing condition. Single caging reduced the extent of social signaling, even though animals were in visual and auditory contact. Rates of affiliative behaviors increased and time spent alone decreased in post-reunion social groups compared to pre-separation social groups (P ’s 0.01). The results indicate that chronic social separation in this group-living species may exacerbate atherosclerosis via altered autonomic activity, as evidenced by higher heart rates during social separation. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Cardiovascular disease; Cynomolgus monkeys; Heart rate; Ovarian function; Psychosocial stress; Social isolation 1. Introduction A lack of social support is associated with increased risk of coronary heart disease (CHD) morbidity and mortality in human beings [1]. Moreover, social support has been associated with better recovery in individuals who have had a clinical event [2]. Nonetheless, the mechanisms by which social support mediates the dis- ease process in CHD are not fully understood. For example, it is unclear whether social support modulates the progression of CHD via effects on actual biological mechanisms, social influences encouraging more health- ful behaviors, or a combination of these [3]. Analogous with human beings, single-caged female cynomolgus monkeys (Macaca fascicularis ) develop more coronary artery atherosclerosis (CAA) than do their socially housed counterparts [4]. In neither humans nor mon- keys are the physiologic mechanisms mediating these effects known with certainty. However, stress-induced elevations in sympathetic activity are thought to in- crease the risk of CHD in human beings [5], while stress-induced increases in casual (i.e. measured at rest) heart rates as well as elevated heart rate reactivity to a standardized psychosocial stressor are associated with increased CAA in monkeys [6]. Furthermore, in female monkeys, atherosclerosis is also potentiated by stress- related ovarian impairment [7 – 9]. In epidemiologic studies of human beings, it is im- possible to control for all extraneous variables. There- fore, use of a relevant animal model allows for more stringent experimental control. Female cynomolgus * Corresponding author. Tel.: +1 336 7161524; fax: +1 336 7161515; e-mail: cshively@cpm.bgsm.edu 0021-9150/98/$19.00 © 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S0021-9150(97)00277-3