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 sympathetic-adrenomedullary and pituitary-adrenocortical systems, mediate psychosocial influences on disease, evidence directly supporting this hypothesis 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 pathologic process--disease of the coronary vasculature--and emphasizing experimental evidence linking such disease to both behavior and sympathoadrenal activation in nonhuman primates. In cynomolgus monkeys, it is found that several psychosocial variables, e.g., social instability, behavioral dominance (in males), and subordination (in females), promote coronary atherogenesis, either independently or in interaction. Animals exhibiting a heightened cardiac responsivity to stress (reactions of probable sympathetic origin) also develop the most extensive coronary lesions and beta-adrenoreceptor blockade prevents the behavioral exacerbation 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 research programs might elucidate the influence of behavior and neuroendocrine factors on the pathogenesis of other disease states and conditions, including susceptibility to infection.