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Updated: Aug 10, 2025

Stress-Enhanced Fear Learning, a Robust Rodent Model of Post-Traumatic Stress Disorder
Published on: October 13, 2018
Multiverse analyses of fear acquisition and extinction retention in posttraumatic stress disorder
Michael W Lewis1,2, Daniel E Bradford3, Edward F Pace-Schott2,4
1Center for Depression, Anxiety, and Stress Research, McLean Hospital, Belmont, Massachusetts, USA.
Abstract:
Persistent fear is a cardinal feature of posttraumatic stress disorder (PTSD), and deficient fear extinction retention is a proposed illness mechanism and target of exposure-based therapy. However, evidence for deficient fear extinction in PTSD has been mixed using laboratory paradigms, which may relate to underidentified methodological variation across studies. We reviewed the literature to identify parameters that differ across studies of fear extinction retention in PTSD. We then performed Multiverse Analysis in a new sample, to quantify the impact of those methodological parameters on statistical findings. In 25 PTSD patients (15 female) and 36 trauma-exposed non-PTSD controls (TENC) (20 female), we recorded skin conductance response (SCR) during fear acquisition and extinction learning (day 1) and extinction recall (day 2). A first Multiverse Analysis examined the effects of methodological parameters identified by the literature review on comparisons of SCR-based fear extinction retention in PTSD versus TENC. A second Multiverse Analysis examined the effects of those methodological parameters on comparisons of SCR to a danger cue (CS+) versus safety cue (CS-) during fear acquisition. Both the literature review and the Multiverse Analysis yielded inconsistent findings for fear extinction retention in PTSD versus TENC, and most analyses found no statistically significant group difference. By contrast, significantly elevated SCR to CS+ versus CS- was consistently found across all analyses in the literature review and the Multiverse Analysis of new data. We discuss methodological parameters that may most contribute to inconsistent findings of fear extinction retention deficit in PTSD and implications for future clinical research.
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