do not commonly confront acute, life-threatening assault. Instead, contemporary humans face ill-defined, diffuse, often chronic threats that cannot be resolved by fight or flight. Nevertheless, the ancient physiologic stress response is triggered when one experiences, for example, a threat to social position, damage to important interpersonal relationships, loss of possessions, or barriers to the achievement of goals. Because many difficulties of contemporary life and their accompanying stress cannot be rapidly resolved—as could many physical stressors—the stress response persists, homeostasis is not restored, and the response becomes dysfunctional rather than adaptive. An increasing body of evidence indicates that stress is a potent contributor to illness (Cohen and Herbert, 1996; Cohen et al., 1991; Hermann et al., 1995; Kiecolt-Glaser et al., 1996; McEwen, 1998). The continued and unproductive activation of the stress response, including the failure to shut off this response when it is not needed, called allostatic load, is discussed below.

The stress response is one aspect of an array of biologic and behavioral processes that either protect or cause damage. For example, secretion of stress-related hormones, such as cortisol and the catecholamines (epinephrine and norepinephrine), typically varies in a daily rhythm that is entrained by the light/dark cycle and by sleep/waking patterns that are part of normal daily life. But chronic increase in cortisol throughout the diurnal cycle is associated with negative consequences, such as accelerated bone mineral loss and hyperglycemia. Because the subjective experience of stress does not always correlate with physiological response (Kirschbaum et al., 1999), long-term measurement of hormone concentrations and of the processes that they regulate (for example, blood cholesterol concentration, fat accumulation, immune function, atrophy of brain structures, blood pressure), constitute an important way to connect life experience and the risk of disease.

Allostasis and Allostatic Load

An important new attempt to understand the relationships between environmental and behavioral challenges and stressors, the physiological responses to these events, and disease uses the terms allostasis and allostatic load. Allostasis is the maintenance of overall stability (homeostasis) through the constant adjustment and balancing of various components in the process of adapting to challenge. Sterling and Eyer (1988) first used the term to describe cardiovascular system adjustments in response to rest



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