The hypothalamic-pituitary-adrenal axis in PTSD: Pathophysiology and treatment interventions

Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 8;89:361-379. doi: 10.1016/j.pnpbp.2018.10.010. Epub 2018 Oct 17.


Questions of how altered functioning of the hypothalamic pituitary adrenal (HPA) axis contribute to the development and maintenance of posttraumatic stress disorder (PTSD) have been the focus of extensive animal and human research. As a rule, results have been inconsistent across studies, likely due to a variety of confounding variables that have received inadequate attention. Important confounding factors include the effects of early life stress, biological sex, and the glucocorticoid used for interventions. In this manuscript we review: 1) the literature on identified abnormalities of HPA axis function in PTSD, both in terms of basal functioning and as part of challenge paradigms; 2) the role of HPA axis function pre- and immediately post-trauma as a risk factor for PTSD development; 3) the impact of HPA axis genes' allelic variants and epigenetic modifications on PTSD risk; 4) the contributions of HPA axis components to fear learning and extinction; and 5) therapeutic manipulations of the HPA axis to both prevent and treat PTSD, including the role of glucocorticoids as part of medication enhanced psychotherapy.

Keywords: Corticotropin releasing hormone; Cortisol; Dexamethasone; Glucocorticoid; Memory; Trauma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Pituitary-Adrenal System / physiopathology*
  • Stress Disorders, Post-Traumatic / physiopathology*
  • Stress Disorders, Post-Traumatic / therapy