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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).

Veterans are at increased risk of comorbid posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) relative to civilians. Few studies have explored the association between distinct PTSD symptoms and AUD in veterans, and existing findings are highly discrepant. This study aimed to address this gap and equivocal association by evaluating which PTSD symptom clusters are most associated with AUD in a veteran sample using the 7-factor 'hybrid' model of PTSD. Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study (NHRVS), a nationally representative survey of 4069 U.S. veterans. Veterans completed self-report measures to assess current PTSD symptoms and AUD. Multivariable logistic regression and relative importance analyses were conducted to examine associations between the 7-factor model of PTSD symptoms and AUD. Adjusting for sociodemographic, military, trauma factors, and depressive symptoms, scores on the dysphoric arousal (20.7% relative variance explained [RVE]) and externalizing behaviors (19.0% RVE) symptom clusters were most strongly associated with AUD in the full sample, while externalizing behaviors (47.7% RVE), anxious arousal (23.9% RVE), and dysphoric arousal (12.4%) accounted for the majority of explained variance in veterans who screened positive for PTSD. Results of this nationally representative study of U.S. veterans highlight the importance of externalizing behaviors and arousal symptoms of PTSD as potential drivers of AUD in this population. The 7-factor hybrid model of PTSD provides a more nuanced understanding of PTSD-AUD associations, and may help inform risk assessment and more personalized treatment approaches for veterans with and at-risk for AUD.

Introduction This study investigated the role of coping strategies in mediating the relationship between the 7-factor model of posttraumatic stress disorder (PTSD) symptoms and alcohol misuse in veterans. Methods Data were analyzed from 615 veterans from a nationally representative study of U.S. veterans who met criteria for probable full or subthreshold PTSD. Path analyses examined the role of self-sufficient, socially-supported, and avoidant coping strategies in mediating associations between PTSD symptom clusters and alcohol use disorder (AUD), alcohol consumption, and alcohol-related consequences. Results Negative affect PTSD symptoms were associated with AUD through increased use of avoidant coping. Additionally, dysphoric arousal PTSD symptoms were associated with AUD; avoidant coping was associated with AUD and increased alcohol consumption; self-sufficient coping was associated with reduced AUD likelihood anhedonia symptoms with decreased use of self-sufficient coping; and negative affect with decreased use of socially-supported coping and increased use of avoidant coping. Conclusions Results underscore the importance of avoidant coping strategies as potential mediators of the relation between PTSD symptoms and AUD. Interventions designed to mitigate engagement in avoidant coping strategies, and to bolster engagement in self-sufficient and socially-supported strategies may help reduce alcohol misuse in veterans with full or subthreshold PTSD.

Nicotine has recently been shown to enhance the motivational value of non-nicotine stimuli in nonhumans. To investigate whether nicotine also enhances reward in humans, we used a virtual translation of the conditioned place preference (CPP) paradigm to examine nicotine's reward-enhancing effects using a low-dose 2 mg nicotine lozenge targeted to a mild use population.

The aim of this experiment was to examine the extent to which eating disorder risk affects the strength of food-reward conditioning. Eighty food-restricted undergraduates were placed into a VR environment consisting of two visually distinct rooms. Participants underwent multiple pairing sessions in which they were confined into one of the two rooms and explored a VR environment. Room A was paired with real-life MMs for three sessions, and Room B was paired with no food for three sessions. After a short delay, a test session was administered, and participants were given free access to the entire VR environment for 5 min. Participants also completed the Eating Attitudes Test (EAT-26; [11]), which is a standard screening tool of eating disorder risk. Participants displayed a significant conditioned place preference for the VR room previously paired with food, and they displayed a significant explicit preference for the MM-paired room in a forced-choice test. There was a significant positive correlation between place preference strength and scores on the dieting subscale of the EAT-26. Additionally, ratings of the no-food room were significantly lower as dieting scores increased. This suggests that components of eating disorder risk can influence basic conditioning strength to places associated with food reward. For both males and females, additional correlations between eating disorder risk subscales and conditioning variables are discussed, and implications for future research are proposed in hopes of understanding how conditioning paradigms can provide insight into treating and preventing eating disorders.

Nicotine has been shown to enhance the reinforcement and reward-responsiveness of non-nicotine stimuli. To determine whether nicotine enhances the strength of conditioning to context, undergraduate participants with varying levels of nicotine dependence were recruited for a two-day study and tested on a virtual reality (VR) conditioned place preference (CPP) paradigm. On day one, participants explored two virtual rooms where they received multiple pairings of M&M rewards in one room and no rewards in the other room, followed by a free-access test session with no rewards. On day two, participants received three test sessions to assess extinction. Subsequently, participants received M&Ms. in a novel context and were then tested for reinstatement. Prior to testing on each day, subjects were administered either nicotine (4mg) or placebo lozenges, in a between-subjects, four-group, 2×2 design (nicotine or placebo on days 1 and 2). After conditioning on day one, only participants who received placebo exhibited a CPP by spending significantly more time in the room previously-paired with M&Ms. Contrary to our hypothesis, nicotine-treated participants did not display a significant CPP, and there were no significant differences between treatment groups. However, post hoc analysis indicated that in a subset of participants with greater nicotine dependence, the nicotine group displayed a CPP by rating the M&M-paired room as significantly more enjoyable than those who received placebo. Additionally, while neither treatment group showed significant place preferences during the first two extinction sessions on Day 2, individuals who received nicotine on Day 1 or placebo on Day 2 spent significantly more time in the M&M-paired room during the final extinction session. Finally, those who received nicotine on Day 2 exhibited significantly greater reinstatement compared to placebo-treated participants. These results partially support preclinical evidence that nicotine can affect learning, extinction, and reinstatement.

The goal of this experiment was to examine whether a conditioned place preference could be established in humans using a secondary reinforcer that provided little obvious reward to the participants. Two experiments were conducted to answer this question. In Experiment 1, 244 undergraduates were placed into a VR environment consisting of two visually distinct rooms connected by a door. Throughout the experiment, one room was randomly paired with occasional point rewards while the other unique room was never paired with rewards. Participants received thee pairings in each room. After a short break, a test session was administered, and participants were given free access to the entire VR environment and no point rewards were administered. On the test day, we observe that participants displayed a significant CPP for the room paired with points, as evidenced by significant differences in rating each of the rooms in terms of enjoyment. In Experiment 2, 77 undergraduates were tested using a biased conditioning approach in which an initial test session was conducted to obtain the participant's preferred room bias, and then the least-preferred room was designated as the points reward room for each participant. Using this biased conditioning approach, participants spent a significantly greater amount of time in the points-paired room. In this case, participants showed preferences based on explicit and implicit measures. These results suggest new approaches to examine the role of secondary reinforcers in nontraditional addictions such as internet, gaming, and gambling dependencies.