resist infection or other challenge, thereby enhancing the effectiveness of immune responses. But adrenal steroids also can increase allostatic load and suppress immune system response when they are secreted chronically or when their release from the adrenal cortex is not terminated properly.

Allostatic load is associated with at least four patterns of long-term harm to the body. The first is a perception of excessive stress. This can take the form of repeated events of various types that cause recurring increases in the release of stress mediators. For example, the amount and frequency of economic hardship are good predictors of decline in physical and mental functioning and even death (Lynch et al., 1997b). The second pattern involves a failure to adapt to recurrence of the same stressor. This leads to overexposure to stress mediators because of the failure to dampen response to a repeated event. Most people, for example, adapt to repeated public-speaking challenges, but some continue to show elevated cortisol concentrations, which indicate a failure to adapt (Kirschbaum et al., 1995). The third pattern entails the failure to terminate the hormonal stress response or the lack of appearance of the normal trough in the daily cortisol release pattern. Examples are increased blood pressure caused by work-related stress (Gerin and Pickering, 1995), increased evening cortisol and hyperglycemia caused by sleep deprivation (Van Cauter et al., 1997), and the chronically elevated cortisol that often accompanies depressive illness (Michelson et al., 1996). The fourth pattern involves inadequate release of hormones, thus allowing other systems, such as inflammatory cytokines, to become overactive. In the Lewis rats, for example, inadequate release of cortisol is associated with increased susceptibility to inflammatory and autoimmune disturbances (Sternberg, 1997; Sternberg et al., 1996).

Early Development Influences Long-Term Effects of Stress

Developmental influences are implicated in susceptibility to stress-related disorders. Classic work by Levine et al. (1967), Denenberg and Haltmeyer (1967), and Ader (1968), shows that the handling of neonatal rats by experimenters leads to reduced emotionality and stress hormone reactivity throughout life. In contrast, prenatal stress increases emotionality and stress hormone reactivity throughout the life of the animal. Post-natal handling reverses the effects of prenatal stress (Fride et al., 1986; Wakschlak and Weinstock, 1990). Handling is believed to increase maternal licking and grooming of pups, which are associated with reduced



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