title: High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies.
abstract: 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.
authors: Division of Psychiatry, The State of Israel Ministry of Health, The Chaim Sheba Medical Center, Sackler Medical School, Tel-Aviv University, Tel Hashomer, Israel.
authors: Joseph
authors: J
authors: Zohar
authors: Hila
authors: H
authors: Yahalom
authors: Nitsan
authors: N
authors: Kozlovsky
authors: Shlomit
authors: S
authors: Cwikel-Hamzany
authors: Michael A
authors: MA
authors: Matar
authors: Zeev
authors: Z
authors: Kaplan
authors: Rachel
authors: R
authors: Yehuda
authors: Hagit
authors: H
authors: Cohen
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology; D001921:Brain / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D049229:Dendritic Spines / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D016622:Silver Staining; D013313:Stress Disorders, Post-Traumatic / Q000209:etiology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000188:drug therapy / Q000473:pathology; D013997:Time Factors; D015599:Trauma Severity Indices; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D006854:Hydrocortisone