The body’s principal adaptive responses to stress stimuli are mediated by an intricate stress system, which includes the
hypothalamic-pituitary-adrenocortical (HPA) axis and the sympathoadrenal system (SAS). Dysregulation of the system,
caused by the cumulative burden of repetitive or chronic environmental stress challenges (allostatic load) contributes to the
development of a variety of illnesses including hypertension, atherosclerosis, and the insulin-resistance–dyslipidemia syndrome,
as well as certain disorders of immune function. The brain’s limbic system, particularly the hippocampus and
amygdala, is also intimately involved in the stress response. Chronically elevated corticosteroid levels induced by persisting
stress may adversely affect hippocampal structure and function, producing deficits of both memory and cognition. The ability
of stress to cause illness in humans is most clearly exemplified by post-traumatic stress disorder (PTSD), which consists of
a predictable constellation of distressing behavioral symptoms and physiological features. An appreciable proportion of the
observed variance in vulnerability to PTSD is attributable to genetic factors. The relationship of this disorder to its precipitating
cause—a recent, severely traumatic event—is unambiguous. The neuroendocrinology of PTSD is noteworthy, being
characterized in many adult victims by enhanced negative feedback sensitivity of glucocorticoid receptors in the stress
response system, and lower than normal urinary and plasma cortisol levels. Adult patients with PTSD also have been shown
to exhibit exaggerated catecholamine responses to trauma-related stimuli. On the other hand, severely maltreated prepubertal
children with PTSD continue to excrete greater than normal urinary cortisol, catecholamines, and dopamine years after
disclosure of the causative abuse.