Cortisol and the Hypothalamic-Pituitary-Adrenal Axis in PTSD

The acute stress response includes activation of the hypothalamic-pituitary-adrenal (HPA) axis, which leads to the release of cortisol, a glucocorticoid. Through negative feedback inhibition at the pituitary, cortisol ultimately acts to contain the stress response and return the body to homeostasis once safety is established. However, early neuroendocrine studies of posttraumatic stress disorder (PTSD) found that while catecholamines and corticotropin-releasing factor (CRF) appeared to be elevated in PTSD, cortisol levels were unexpectedly found to be lower than in controls. Corticotropin-releasing hormone (CRH) stimulates the release of adrenocorticotropic hormone (ACTH) from the pituitary, which in turn stimulates the production of cortisol in the adrenal cortex. Furthermore, cortisol can be measured in saliva, blood, urine, or cerebrospinal fluid, and levels will vary depending on the method of analysis, time of day, and context of the assessment.