A systematic review evaluating PTSD treatment effects on intermediate phenotypes of PTSD.

Abstract

Objective: Although the efficacy of evidence-based treatments for posttraumatic stress disorder (PTSD) has been well established, high rates of treatment dropout and/or nonresponse or under-response to treatment suggest a need to explore novel treatment approaches. Most current research has focused on DSM-based categorical outcomes as primary indicators of treatment response, which may obscure the phenotypic heterogeneity of PTSD and limit the ability to map symptoms to underlying neurobiology. This systematic review aimed to identify intermediate phenotypes (IPs) of PTSD and evaluate IP sensitivity to PTSD treatments. Method: Five databases were searched for empirical studies published in English between January 1, 2010 and August 1, 2022 examining behavioral and pharmacological PTSD treatment effects on biobehavioral PTSD outcomes. Results: Twenty-two studies met the inclusion criteria. Most studies evaluated behavioral treatment outcomes (n = 20), while only two studies evaluated pharmacological interventions. Five PTSD IPs were identified, including “impairments in working memory,” “alterations in cognitive control,” “unstable threat processing,” “heightened fear or startle response,” and “disturbances in sleep and wakefulness.” This review offers preliminary support to suggest the utility of IP measures in assessing treatment efficacy; however, risk of bias and methodological limitations constrain the validity and generalizability of the results. Conclusions: The paucity of research combined with the heterogeneity of study methodologies and significant study limitations makes it difficult to draw strong conclusions regarding IP sensitivity to treatment. However, the existing body of research incorporating this framework shows potential for the IP approach to improve the translation of treatment efficacy from clinical trials to clinical settings.