Neurobiological Effects of Trauma

Health Consequences of Repeated or Prolonged Stress: Allostasis and Allostatic Load

The term allostasis was coined to denote the dynamic process through which the body adapts to daily and acute stressors, both predictable and unpredictable, and maintains its ability to regulate biochemical processes important for survival. When faced with unexpected, sudden stressful events, the brain responds by activating the two main branches of the stress-response system. Named for central biochemical mediators of these systems, these have been termed the locus coeruleus norepinephrine (LC-NE) system and the corticotropin-releasing hormone (CRH) system. The primary molecular mediators of these two systems are the catecholamines (norepinephrine, epinephrine, and dopa-mine) and the glucocorticoids (cortisol), respectively. Although protective in the short run, these systems can have damaging effects if activated repeatedly or for prolonged periods. CRH is a neuropeptide secreted by the neurons of the hypothalamus and by neurons communicating between brain regions such as the amygdala and LC that are implicated in emotional responses to stress. The LC-NE system and CRH system interact with each other, and together integrate various behavioral, autonomic, and hormonal responses to stress within the central [Page 404]nervous system (CNS). For example, CRH secreted by the hypothalamus activates the release of adre-nocorticotropic hormone (ACTH) from the anterior pituitary gland into the bloodstream, which in turn stimulates the synthesis and secretion of glu-cocorticoids and mineralocorticoids by the adrenal glands. Circulating glucocorticoids in turn inhibit the release of further CRH and ACTH through a complex negative feedback system, completing the neuroendocrine loop known as the hypothalamic-pituitary-adrenal (HPA) axis.

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