THE PATHOGENICITY OF BEHAVIOR AND ITS NEUROENDOCRINE MEDIATION - AN EXAMPLE FROM CORONARY-ARTERY DISEASE

Although it is frequently hypothesized that perturbations of the body' s principal axes of neuroendocrine response, especially the sympatheti c-adrenomedullary and pituitary-adrenocortical systems, mediate psycho social influences on disease, evidence directly supporting this hypoth esis is sparse at best and, for most disease entities, nonexistent. In this article, we illustrate a research strategy aimed at elucidating the role of behavior in disease pathogenesis by focusing on a single p athologic process-disease of the coronary vasculature-and emphasizing experimental evidence linking such disease to both behavior and sympat hoadrenal activation in nonhuman primates. In cynomolgus monkeys, it i s found that several psychosocial variables, e.g., social instability, behavioral dominance (in males), and subordination (in females), prom ote coronary atherogenesis, either independently or in interaction. An imals exhibiting a heightened cardiac responsivity to stress (reaction s of probable sympathetic origin) also develop the most extensive coro nary lesions and beta-adrenoceptor blockade prevents the behavioral ex acerbation of atherosclerosis. Social stress causes injury to arterial endothelium (also preventable by adrenoreceptor blockade) and, among chronically stressed animals, impairs endothelium-dependent vasomotor responses of the coronary arteries. It is suggested that similar resea rch programs might elucidate the influence of behavior and neuroendocr ine factors on the pathogenesis of other disease states and conditions , including susceptibility to infection.