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Author Notes:

Correspondence: Tanja Jovanovic, PhD, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 49 Jesse Hill Jr. NE, Atlanta, GA 30303, tjovano@emory.edu.

Author Contributions: Authors Jovanovic, Norrholm, Ressler and Rothbaum designed and organized the studies and wrote the protocols.

Authors Michopoulos, Stevens and Glover collected the data.

Authors Michopoulos and Jovanovic undertook the statistical analyses.

Authors Michopoulos, Stevens, Glover, Jovanovic, Norrholm, Ressler and Rothbaum contributed to the analysis and interpretation of the data.

Authors Michopoulos and Jovanovic wrote the first draft of the manuscript.

All authors contributed to and have approved the final manuscript.

Acknowledgments: We thank Alex Rothbaum, Allen Graham, Angelo Brown and the nurses and staff of the Grady GCRC for their assistance with data collection and support.

Disclosures: Dr. Rothbaum owns equity in Virtually Better, Inc. that creates virtual reality products.

The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies.

Dr. Rothbaum receives royalties from Oxford University Press, Guilford, APPI, and Emory University and received one advisory board payment from Genentech.

All other authors have nothing to disclose.

Subjects:

Research Funding:

This work was supported by the Howard Hughes Medical Institute, the National Institute for Health (R01 MH094757, KJR; R21 MH092576 TJ), the National Institute of Child Health and Human Development (K12 HD085850, VM) and the Brain and Behavior Research Foundation.

Support was also provided by the Emory and Grady Memorial Hospital General Clinical Research Center (GCRC), NIH National Centers for Research Resources (M01 RR00039), and the Burroughs Wellcome Fund.

Dr. Rothbaum has funding from Wounded Warrior Project, Department of Defense Clinical Trial Grant No.W81XWH-10-1-1045, “Enhancing Exposure Therapy for PTSD: Virtual Reality and Imaginal Exposure with a Cognitive Enhancer” and McCormick Foundation “Brave Heart: MLB’s Welcome Back Veterans SouthEast Initiative.”

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Endocrinology & Metabolism
  • Neurosciences
  • Psychiatry
  • Neurosciences & Neurology
  • PTSD
  • Dexamethasone
  • Fear extinction
  • Safety discrimination
  • Fear-potentiated startle
  • POSTTRAUMATIC-STRESS-DISORDER
  • CORTICOTROPIN-RELEASING-FACTOR
  • MEDIAL PREFRONTAL CORTEX
  • TRAUMA-EXPOSED MEN
  • CHILDHOOD TRAUMA
  • MEMORY CONSOLIDATION
  • BASOLATERAL AMYGDALA
  • CORTISOL SUPPRESSION
  • DEPRESSIVE DISORDER
  • D-CYCLOSERINE

Dexamethasone facilitates fear extinction and safety discrimination in PTSD: A placebo-controlled, double-blind study

Tools:

Journal Title:

Psychoneuroendocrinology

Volume:

Volume 83

Publisher:

, Pages 65-71

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Psychophysiological hallmarks of posttraumatic stress disorder (PTSD) include exaggerated fear responses, impaired inhibition and extinction of conditioned fear, and decreased discrimination between safety and fear cues. This increased fear load associated with PTSD can be a barrier to effective therapy thus indicating the need for new treatments to reduce fear expression in people with PTSD. One potential biological target for reducing fear expression in PTSD is the hypothalamic-pituitary-adrenal (HPA) axis, which is dysregulated in PTSD. Recent translational rodent studies and cross-sectional clinical studies have shown that dexamethasone administration and the resulting suppression of cortisol in individuals with PTSD leads to a decrease in the fear responses characteristic of PTSD. These data, taken together, suggest that dexamethasone may serve as a novel pharmacologic intervention for heightened fear responses in PTSD. We conducted a double-blind, placebo-controlled trial to test our hypothesis that dexamethasone administration and the concomitant suppression of HPA axis hyperactivity would attenuate fear expression and enhance fear extinction in individuals with PTSD. Study participants (n = 62) were recruited from Grady Memorial Hospital in Atlanta, GA. Participants were randomized to receive dexamethasone or placebo prior to fear conditioning and extinction, in a counterbalanced design (treatments separated by a week). Both PTSD- (n = 37) and PTSD+ (n = 25) participants showed significant startle increases in the presence of the danger signal during placebo and dexamethasone treatments (all p < 0.05). However, only PTSD- control participants showed decreases in fear-potentiated startle across extinction blocks during both conditions (p's ≤ 0.001), with PTSD+ participants showing deficits in fear extinction and safety discrimination in the placebo condition. Notably, extinction and discrimination deficits in PTSD+ subjects were markedly reversed with dexamethasone (p < 0.001). These data suggest that dexamethasone may serve as a pharmacological agent with which to facilitate fear extinction and discrimination in individuals with PTSD.

Copyright information:

© 2017 Elsevier Ltd

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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