Sensitization of the Hypothalamic‐Pituitary‐Adrenal Axis in Posttraumatic Stress Disorder a

Posttraumatic stress disorder (PTSD) is a psychiatric condition that can occur in individuals who have experienced traumatic events. The symptoms of PTSD were initially conceptualized as reflecting a natural process of adaptation to extraordinarily adverse life event~.l-~ However, in recent years prevalence studies have clarified that PTSD only occurs in a percentage of those exposed to trauma."' Furthermore, among trauma survivors who develop this disorder, a substantial proportion appear to show full remission of their symptoms over time.6 This observation demonstrates that chronic PTSD represents a specific type of adaptation to trauma, which may not necessarily reflect typical or even normative stress responsiveness.1° Because PTSD is clearly precipitated by a traumatic event, and because of the original conceptions that this disorder described normative consequences of trauma, initial theories about the biologic underpinnings of PTSD posited that neurobiological alterations in PTSD would be similar to those observed in stress."-13 However, as reviewed in this chapter, the descriptions of actual neurobiologic alterations in PTSD suggest a very different profile in trauma survivors with PTSD from that observed in classical stress studies. Furthermore, trauma survivors with PTSD show different biologic alterations from those of trauma survivors without PTSD. Thus, many of the biologic findings, particularly the neuroendocrine observations, also support the idea that PTSD is a specific type of adaptation to stress that does not necessarily reflect classic or typical responses to stress. This chapter specifically describes findings of hypothalamic-pituitary-adrenal (HPA) axis alterations in PTSD and contrasts these findings with the well-documented observations of HPA axis dysfunction after stress and in psychiatric disorders such as major depression. It is suggested that rather than the classic profile of increased adrenocortical activity and resultant dysregulation of this system described in studies of stress and other psychiatric disorders, trauma survivors with PTSD show evidence