Neuroendocrinology of Posttraumatic Stress Disorder: Focus on the HPA Axis

The hypothalamic-pituitary-adrenal (HPA) axis is activated in response to stressor detection in order to mobilize resources critical for survival. Chronic or extreme stress precipitates dysregulation of the HPA axis concomitant with development of psychopathology, most notably in major depressive disorder. HPA axis alterations have similarly been noted in posttraumatic stress disorder (PTSD). Conversely, PTSD appears to be characterized by lower basal levels of cortisol and greater HPA axis negative feedback, which is thought to be mediated by greater sensitivity of the glucocorticoid receptor. Recent evidence calls into question whether HPA axis alterations represent a preexisting vulnerability or are altered with pathophysiology of the disease and, further, whether these alterations reflect trauma exposure, rather than PTSD per se. Rigorous comparison of participant trauma history, consistency in diagnostic criteria, and systems biology approaches may better inform questions related to an association between changes in the HPA axis and PTSD.