High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: Interplay between clinical and animal studies

Joseph Zohar, Hila Yahalom, Nitsan Kozlovsky, Shlomit Cwikel-Hamzany, Michael A. Matar, Zeev Kaplan, Rachel Yehuda, Hagit Cohen

Research output: Contribution to journalArticlepeer-review


High-dose corticosteroids have been reported to reduce symptoms of acute stress and post-traumatic stress in polytrauma patients and in animal studies. The underlying mechanism of action remains largely unclear. These issues were addressed in parallel in the clinical and preclinical studies below. In this preliminary study, 25 patients with acute stress symptoms were administered a single intravenous bolus of high-dose hydrocortisone (100-140. mg) or placebo within 6. h of a traumatic event in a prospective, randomized, double-blind, placebo-controlled pilot study. Early single high-dose hydrocortisone intervention attenuated the core symptoms of both the acute stress and of subsequent PTSD in patients. High-dose hydrocortisone treatment given in the first few hours after a traumatic experience was associated with significant favorable changes in the trajectory of exposure to trauma, as expressed by the reduced risk of the development of PTSD post-trauma. In parallel, a comparative study of morphological arborization in dentate gyrus and its modulating molecules was performed in stress-exposed animals treated with high-dose hydrocortisone. Steroid-treated stressed animals displayed significantly increased dendritic growth and spine density, with increased levels of brain-derived neurotrophic factor (BDNF) and obtunded postsynaptic density-95 (PSD-95) levels. The animal study provided insights into the potential mechanism of this intervention, as it identified relevant morphological and biochemical associations to the clinical observations. Thus, evidence from clinical and animal studies suggests that there is a "window of opportunity" in the early aftermath of trauma to help those who are vulnerable to the development of chronic PTSD.

Original languageEnglish
Pages (from-to)796-809
Number of pages14
JournalEuropean Neuropsychopharmacology
Issue number11
StatePublished - Nov 2011


  • Animal model
  • Brain-derived neurotrophic factor (BDNF)
  • Dendritic arborization
  • Hydrocortisone
  • Postsynaptic density-95 (PSD-95)
  • Posttraumatic stress disorder
  • Secondary prevention


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