Multiverse analyses of fear acquisition and extinction retention in posttraumatic stress disorder

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.

Predicting Fear Extinction in Posttraumatic Stress Disorder

“…When excluding the startle variables, this difference increased, with the average number of the predictor criteria being 1.12 for early extinction versus 0.5 for late extinction. This aligns with previous research, indicating that the relationship between fear extinction and clinical variables is influenced by the temporal dynamics and operationalization of fear extinction [ 9 , 18 ]. Therefore, future studies focusing on clinical correlates and predictors of fear extinction may be more likely to find an effect during early extinction, where there is generally a greater variability.…”

“…Numerous clinical and self-report measures have been associated with fear extinction in some studies, but their findings have not consistently replicated [ 4 , 6 , 7 , 8 ]. Thus, it may be beneficial to apply novel bottom-up statistical approaches to simultaneously evaluate multiple predictors of fear extinction in a single study [ 4 , 9 , 10 ]. Penalized regressions are a class of machine learning approaches used in clinical psychology research to increase predictive accuracy, improve generalizability, and select predictors [ 11 , 12 , 13 ].…”

“…Despite the clear clinical relevance of fear extinction in PTSD treatment [ 15 ], there is no consensus regarding whether current PTSD diagnoses or symptom severity robustly predict fear extinction [ 7 , 9 ]. For example, some studies have found evidence of deficient fear extinction learning in PTSD patients versus controls, while others have not (as reviewed by [ 7 ]).…”

“…The findings have been similarly mixed when examining PTSD symptom severity [ 16 , 17 ] and specific PTSD symptom clusters [ 16 , 18 , 19 , 20 ] as predictors of fear extinction. Several explanations for these inconsistent findings have been proposed, including: the biological [ 18 , 21 ] and clinical [ 21 , 22 ] heterogeneity of PTSD, the insufficient statistical power of previous studies [ 7 ], and the methodological heterogeneity across previous studies [ 9 , 23 ]. These findings align with prior calls for an increased emphasis on the within-group differences in fear extinction in PTSD [ 21 , 22 ].…”

“…These findings align with prior calls for an increased emphasis on the within-group differences in fear extinction in PTSD [ 21 , 22 ]. Further, they highlight a need for strategies to improve predictive performance and generalizability [ 7 , 9 , 23 ]. Ultimately, the accurate and generalizable prediction of fear extinction in PTSD samples may inform advances in precision extinction-based treatments [ 3 , 15 ].…”