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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.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.Twenty-two studies met the inclusion criteria. Most studies evaluated behavioral treatment outcomes (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. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Nicotine has been shown to facilitate hippocampal-dependent context fear conditioning (FC), but not hippocampal-independent delay cued fear conditioning. Studies examining the effects of nicotine on learned fear have been exclusively limited to nonhumans. The present study aimed to translate nonhuman findings by investigating the effects of nicotine on cued and context fear in humans using a virtual reality (VR) analog of the fear conditioning task. Sixty-seven nicotine-using undergraduates were randomly assigned to receive either a 2 mg nicotine or placebo lozenge prior to conditioning. During conditioning, participants were confined to a virtual room and were conditioned to green floodlight presentations (conditioned stimulus [CS +]) paired with a wrist shock (unconditioned stimulus [US]). A red floodlight served as the CS- during which no shock occurred. Delay cued and context fear testing immediately followed conditioning. Physiological skin conductance responses (SCRs) were recorded continuously throughout all sessions. Nicotine enhanced context fear conditioning such that SCRs to the shock-paired context were significantly greater for the nicotine group than the placebo group. Nicotine did not enhance delay cued fear. Exploratory analyses examining the relationship between fear conditioning and self-reported anxiety revealed that relative to those with lower levels of trait anxiety, nicotine-treated individuals with higher trait anxiety levels were less likely to demonstrate differential conditioning to the shock-paired cue. These findings support abundant nonhuman literature indicating that nicotine facilitates hippocampus-dependent versions of fear conditioning in humans. Results also suggest a role for dysregulated safety learning in pathological anxiety, which may be exacerbated by nicotine use. (PsycInfo Database Record (c) 2022 APA, all rights reserved).