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Author Notes:

Corresponding author. Atlanta VAMC, MHSL 116A, 1670 Clairmont Road, Decatur, GA 30033-4098, USA. seth.norrholm@va.gov, snorrho@emory.edu

We thank Kemp Anderson, Cliffe Kwon, Taylor Warren, Alexander McCarthy, Ilana Olin, and Cole Youngner for their assistance in the performance of study procedures, analysis of study data, and in the preparation of this manuscript.

Dr. Rothbaum is a consultant to and owns equity in Virtually Better, Inc., which creates virtual environments; however, Virtually Better did not create the Virtual Iraq environment tested in this study; the terms of these arrangements have been reviewed and approved by Emory University in accordance with its conflict of interest policies.


Research Funding:

Dr. Rothbaum also has funding from Department of Defense Clinical Trial Grant W81XWH-10-1-1045 (“Enhancing Exposure Therapy for PTSD: Virtual Reality and Imaginal Exposure With a Cognitive Enhancer”), from NIMH grant U19 MH-069056 (“The Emory-MSSM-GSK-NIMH Collaborative Mood and Anxiety Disorders Initiative”), from NIMH grant R01 MH-70880 (“A Cognitive Enhancer May Facilitate Behavioral Exposure Therapy”), from NIMH grant R01 MH-094757 (“Prospective Determination of Psychobiological Risk Factors for Posttraumatic Stress”), from a Brain and Behavior Research Foundation (NARSAD) Distinguished Investigator Grant (“Optimal Dose of Early Intervention to Prevent PTSD”), and from the McCormick Foundation (“BraveHeart: MLB’s Welcome Back Veterans Southeast Initiative”); she has received previous support from Transcept Pharmaceuticals (“A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Low-Dose Ondansetron for Adjunctive Therapy in Adult Patients With Obsessive-Compulsive Disorder Who Have Not Adequately Responded to Treatment With a Serotonin Reuptake Inhibitor”); she receives royalties from Oxford University Press, Guilford, American Psychiatric Publishing, and Emory University; and she received one advisory board payment from Genentech. Drs. Ressler and Davis are founding members of Extinction Pharmaceuticals/Therapade Technologies, which seek to develop D-cycloserine and other compounds for use to augment the effectiveness of psychotherapy; they have received no equity or income from this relationship within the last 3 years; the terms of these arrangements have been reviewed and approved by Emory University in accordance with its conflict of interest policies.

Dr. Duncan has received research support from the Posit Science Corporation and grant support from NIMH and the National Institute on Drug Abuse. The remaining authors report no financial relationships with commercial interests.


  • Social Sciences
  • Psychology, Clinical
  • Psychology
  • Acoustic startle
  • Posttraumatic stress disorder
  • Virtual reality
  • Psychophysiology
  • Exposure therapy
  • Cortisol

Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy

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Journal Title:

Behaviour Research and Therapy


Volume 82


, Pages 28-37

Type of Work:

Article | Post-print: After Peer Review


Baseline cue-dependent physiological reactivity may serve as an objective measure of posttraumatic stress disorder (PTSD) symptoms. Additionally, prior animal model and psychological studies would suggest that subjects with greatest symptoms at baseline may have the greatest violation of expectancy to danger when undergoing exposure based psychotherapy; thus treatment approaches which enhanced the learning under these conditions would be optimal for those with maximal baseline cue-dependent reactivity. However methods to study this hypothesis objectively are lacking. Virtual reality (VR) methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of PTSD. Our goal was to examine the predictive nature of initial psychophysiological (e.g., startle, skin conductance, heart rate) and stress hormone responses (e.g., cortisol) during presentation of VR-based combat-related stimuli on PTSD treatment outcome. Combat veterans with PTSD underwent 6 weeks of VR exposure therapy combined with either D-cycloserine (DCS), alprazolam (ALP), or placebo (PBO). In the DCS group, startle response to VR scenes prior to initiation of treatment accounted for 76% of the variance in CAPS change scores, p < 0.001, in that higher responses predicted greater changes in symptom severity over time. Additionally, baseline cortisol reactivity was inversely associated with treatment response in the ALP group, p = 0.04. We propose that baseline cue-activated physiological measures will be sensitive to predicting patients' level of response to exposure therapy, in particular in the presence of enhancement (e.g., DCS).

Copyright information:

© 2016

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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