Stress

Genetics, Gender, Age: Part 3
by National Institute of Health

(Page 6 of 6)

Early Life Deprivation. In contrast to early life stimulation, early life stressors (separation from the mother for relatively long periods, such as 3 hours per day) may increase the potential for later stressor-promoted HPA activation. Indeed, protracted separation provokes an increase of plasma ACTH and corticosterone and increased behavioral and neuroendocrine reactivity to stressors encountered during adulthood. Paralleling the effects of early life deprivation in which young animals were made ill by the administration of a bacterial toxin - several aspects of the HPA response to stressors during adulthood were increased. Of course, bacterial toxins may induce fever, possibly altering the mother's behavior toward the young (elevations of body temperature may serve as a cue for termination of nursing), which, in turn, precipitates the altered response to subsequently encountered stressors. It remains to be determined whether metabolic stressors that do not elevate body temperature also induce such long-term effects. In any case, early life trauma, which includes not only separation from the mother but also bacterial infection, appears to have potentially far-reaching implications. Thus, various early life experiences in newborn humans might significantly affect reactivity to stressors encountered during adulthood.

Regulating the Stress Response

The maintenance of a relatively stable balance of physiological functions (homeostasis) is constantly challenged by illness; injury; hostile environmental conditions; unpleasant emotional states; and even certain normal functions, such as sexual activity and exposure to new environments. The body's response to such stressors is regulated largely by interactions among the hypothalamus, pituitary gland, and adrenal glands, together termed the HPA axis. In response to potentially harmful stimuli, the hypothalamus, which is located near the base of the brain, secretes two hormones that travel directly to the adjacent pituitary gland. These two hormones, corticotropinreleasing hormone (CRH) and arginine vasopressin (AVP), promote the secretion of adrenocorticotropic hormone (ACTH) from the pituitary gland. Traveling through the bloodstream, ACTH reaches the adrenal glands, which are located on top of the kidneys. In humans, the adrenal glands respond to ACTH by releasing the steroid hormone cortisol into the bloodstream.2 Cortisol exerts widespread physiological effects throughout the body, acting in concert with other chemical messengers to help direct oxygen and nutrients to the stressed body site and suppress the immune response, while influencing certain functions, such as appetite and satiety; arousal, vigilance, and attention; and mood.

Under normal circumstances, the presence of cortisol in the bloodstream signals the hypothalamus to terminate CRH secretion, thereby preventing overactivity of the stress response. The regulation of a physiological response through inhibition mediated by the end-product of the response is called negative feedback. When negative feedback control of the HPA axis does not operate adequately, as may occur following chronic stress or as a consequence of certain psychiatric disorders (possibly including severe depression), persistent activation of the HPA axis may occur. Damage resulting from HPA overactivity may include suppression of growth, immune system dysfunction, and localized brain cell damage that might result in impairment of learning and memory.

Summary

In response to stressors, a series of behavioral, neurochemical, and immunological changes occur that ought to serve in an adaptive capacity. However, if these systems become overly taxed, the organism may become vulnerable to pathology. Likewise, the biological changes, if sufficiently sustained, may themselves adversely affect the organism's well-being. Several factors may dictate an individual's response to environmental stressors, including characteristics of the stressor (type of stressor and its controllability, predictability, and chronicity); biological factors (age, gender, and genetics); and the subject's previous stressor history and early life experiences. Ultimately, these factors interact to determine the organism's biological responses to environmental stressors; thus, not surprisingly, much interindividual variability exists with respect to the impact of stressors. Of course, the retinue of biological changes and the broad range of variables that influence these outcomes often make it difficult to identify the mechanisms associated with stressor-provoked pathology.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.