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Background Identification of genetic risk factors may inform the prevention and treatment of posttraumatic stress disorder (PTSD). This study evaluates the associations of polygenic risk scores (PRS) with patterns of posttraumatic stress symptoms following combat deployment. Method US Army soldiers of European ancestry (n = 4900) provided genomic data and ratings of posttraumatic stress symptoms before and after deployment to Afghanistan in 2012. Latent growth mixture modeling was used to model posttraumatic stress symptom trajectories among participants who provided post-deployment data (n = 4353). Multinomial logistic regression models tested independent associations between trajectory membership and PRS for PTSD, major depressive disorder (MDD), schizophrenia, neuroticism, alcohol use disorder, and suicide attempt, controlling for age, sex, ancestry, and exposure to potentially traumatic events, and weighted to account for uncertainty in trajectory classification and missing data. Results Participants were classified into low-severity (77.2%), increasing-severity (10.5%), decreasing-severity (8.0%), and high-severity (4.3%) posttraumatic stress symptom trajectories. Standardized PTSD-PRS and MDD-PRS were associated with greater odds of membership in the high-severity v. low-severity trajectory [adjusted odds ratios and 95% confidence intervals, 1.23 (1.06–1.43) and 1.18 (1.02–1.37), respectively] and the increasing-severity v. low-severity trajectory [1.12 (1.01–1.25) and 1.16 (1.04–1.28), respectively]. Additionally, MDD-PRS was associated with greater odds of membership in the decreasing-severity v. low-severity trajectory [1.16 (1.03–1.31)]. No other associations were statistically significant. Conclusions Higher polygenic risk for PTSD or MDD is associated with more severe posttraumatic stress symptom trajectories following combat deployment. PRS may help stratify at-risk individuals, enabling more precise targeting of treatment and prevention programs.

Recently developed measures of genetic liability to suicide attempt may convey unique information regarding an individual’s risk of suicidal behavior. We calculated a polygenic risk score for suicide attempt (SA-PRS) for soldiers of European ancestry who participated in the Army STARRS New Soldier Study (NSS; n = 6573) or Pre/Post Deployment Study (PPDS; n = 4900). Multivariable logistic regression models were fit within each sample to estimate the association of SA-PRS with lifetime suicide attempt (LSA), and to examine whether SA-PRS displayed additive or interactive effects with environmental and behavioral risk/protective factors (lifetime trauma burden, childhood maltreatment, negative urgency impulsivity, social network size, perceived mattering, and dispositional optimism). Age, sex, and within-ancestry variation were included as covariates. Observed prevalence of LSA was 6.3% and 4.2% in the NSS and PPDS samples, respectively. In the NSS model, SA-PRS and environmental/behavioral factors displayed strictly additive effects on odds of LSA. Results indicated an estimated 21% increase in odds of LSA per 1 SD increase in SA-PRS [adjusted odds ratio (AOR; 95% CI) = 1.21 (1.09–1.35)]. In PPDS, the effect of SA-PRS varied by reports of optimism [AOR = 0.85 (0.74–0.98) for SA-PRS x optimism effect]. Individuals reporting low and average optimism had 37% and 16% increased odds of LSA per 1 SD increase in SA-PRS, respectively, whereas SA-PRS was not associated with LSA in those reporting high optimism. Overall, results suggested the SA-PRS had predictive value over and above several environmental and behavioral risk factors for LSA. Moreover, elevated SA-PRS may be more concerning in the presence of environmental and behavioral risk factors (e.g., high trauma burden; low optimism). Given the relatively small effect magnitudes, the cost and incremental benefits of utilizing SA-PRS for risk targeting must also be considered in future work.

COVID-19 pandemic presents an unheralded opportunity to better understand trajectories of posttraumatic stress disorder (PTSD) symptoms across a prolonged period of social disruption and stress. We tracked PTSD symptoms among trauma-exposed individuals in the United States and sought to identify population-based variability in PTSD symptom trajectories and understand what, if any, early pandemic experiences predicted membership in one trajectory versus others. As part of a longitudinal study of U.S. residents during the pandemic, participants who reported at least one potentially traumatic experience in their lifetime (N = 1,206) at Wave 1 (April 2020) were included in the current study. PTSD symptoms were assessed using the PCL-5 at four time points extending to July 2021. Latent growth mixture modeling was used to identify heterogeneous symptom trajectories. Trajectory membership was regressed on experiences from the early stage of the pandemic as measured using the Epidemic-Pandemic Impacts Inventory in a model that controlled for variables with documented associations to PTSD trajectories, including age, sex, income, and trauma history. Four trajectories were identified, categorized as resilient (73.0%), recurring (13.3%), recovering (8.3%), and chronic (5.5%). Emotional and physical health problems and positive changes associated with the early phase of the pandemic were each significant predictors of trajectory membership over and above all other variables in the model. Predictors primarily differentiated the resilient trajectory from each of the other three trajectories. Distinct PTSD symptom trajectories during the COVID-19 pandemic suggest a need for targeted efforts to help individuals at most risk for ongoing distress.

Objectives Depression is a highly heterogeneous disorder, and meta-analyses of mindfulness-based interventions show moderate efficacy for reducing depressive symptoms. However, the mechanisms governing their efficacy remain unclear, highlighting the need for hypothesis-generating analyses to guide future research. Methods We used Bayesian network analysis in three cross-sectional samples (N = 1135) of undergraduates and participants from the community to identify links between individual symptoms of depression and specific facets of mindfulness. In two exploratory studies, we assessed depression using the Patient Health Questionnaire (n = 384) or the Depression Anxiety and Stress Scale (n = 350) and mindfulness using the Five-Facet Mindfulness Scale. Results Across these samples and measures, exploratory analyses indicated that non-judging was a central bridge between facets of mindfulness and symptoms of depression. We confirmed this finding in a pre-registered replication (n = 401) using a recently developed confirmatory testing framework for network analysis. Non-judging was consistently a central bridge in the networks and specifically linked to the symptoms of depression related to feelings of failure and worthlessness. Conclusions These findings provide strong evidence that non-judging is an essential feature of mindfulness in the context of depression and provides direction for future research testing mindfulness-oriented treatment prescriptions for depression. Supplementary Information The online version contains supplementary material available at 10.1007/s12671-021-01726-1.

BackgroundPreclinical findings suggest that transcranial infrared laser stimulation (TILS) improves fear extinction learning and cognitive function by enhancing prefrontal cortex (PFC) oxygen metabolism. These findings prompted our investigation of treating pathological fear using this non-invasive stimulation approach either alone to the dorsolateral PFC (dlPFC), or to the ventromedial PFC (vmPFC) in combination with exposure therapy.MethodsVolunteers with pathological fear of either enclosed spaces, contamination, public speaking, or anxiety-related bodily sensations were recruited for this randomized, single-blind, sham-controlled trial with four arms: (a) Exposure + TILS_vmPFC (n = 29), (b) Exposure + sham TILS_vmPFC (n = 29), (c) TILS_dlPFC alone (n = 26), or (d) Sham TILS _dlPFC alone (n = 28). Post-treatment assessments occurred immediately following treatment. Follow-up assessments occurred 2 weeks after treatment.ResultsA total of 112 participants were randomized [age range: 18–63 years; 96 females (85.71%)]. Significant interactions of Group × Time and Group × Context indicated differential treatment effects on retention (i.e. between time-points, averaged across contexts) and on generalization (i.e. between contexts, averaged across time-points), respectively. Among the monotherapies, TILS_dlPFC outperformed SHAM_dlPFC in the initial context, b = −13.44, 95% CI (−25.73 to −1.15), p = 0.03. Among the combined treatments, differences between EX + TILS_vmPFC and EX + SHAM_vmPFC were non-significant across all contrasts.ConclusionsTILS to the dlPFC, one of the PFC regions implicated in emotion regulation, resulted in a context-specific benefit as a monotherapy for reducing fear. Contrary to prediction, TILS to the vmPFC, a region implicated in fear extinction memory consolidation, did not enhance exposure therapy outcome.

BACKGROUND AND AIMS People with anxiety disorders are more likely to smoke and less likely to succeed when they try to quit. Anxiety sensitivity may underlie both phenomena, such that people with high anxiety sensitivity react to interoceptive distress by avoidance. This study aimed to test the efficacy of an exercise program that induced interoceptive distress and thereby created tolerance to this distress in a safe environment. DESIGN, SETTING AND PARTICIPANTS Randomized clinical trial at four YMCA branches in Austin, Texas, USA. Participants [n = 150; 130 (86.7%) white; 101 (67.3%) female; meanage = 38.6, standard deviation (SD)age = 10.4] were adult, daily smokers with high anxiety sensitivity motivated to quit smoking, who reported no regular moderate-intensity exercise. INTERVENTIONS Participants were assigned a YMCA personal trainer who guided them through a 15-week intervention aerobic exercise program. Participants assigned to the personalized intervention trained at 60-85% of their heart rate reserve (HRR), whereas participants assigned to the control intervention trained at 20-40% of their HRR. Participants in both groups received standard behavioral support and nicotine replacement therapy. MEASUREMENTS The primary outcome was biologically verified 7-day point prevalence abstinence (PPA) at 6-month follow-up. FINDINGS Sixty-one per cent of participants were available at the 6-month follow-up. PPA at 6 months was higher in the personalized intervention than the control intervention [27.6 versus 14.8%; odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.28, 3.80, P = 0.005], assuming missing at random. Anxiety sensitivity declined in both groups with no evidence that this differed between groups. CONCLUSIONS An exercise program of high intensity increased abstinence from smoking in people with high anxiety sensitivity, but may not have done so by reducing anxiety sensitivity.

Optimizing treatment for co-occurring post-traumatic stress disorder and substance use disorder (PTSD+SUD) is critically important. Whereas treatments have been designed that target PTSD+SUD with some success, these treatments do not benefit all. Data-driven approaches that combine person- and variable-centered methods, such as parallel process latent class growth analysis (PP-LCGA) can be used to identify response-to-treatment trajectories across both PTSD symptoms and substance use. The current study employed PP-LCGA separately in two randomized clinical trials (study 1 n = 81, Mean age = 40.4 years, SD = 10.7; study 2 n = 59, Mean age = 44.7 years, SD = 9.4) to examine PTSD symptom response and percentage of days using substances across treatment trials comparing Concurrent Treatment of PTSD and SUD using Prolonged Exposure and Relapse Prevention. Results revealed four PTSD+SUD profiles for study one and three PTSD+SUD profiles for study two. For PTSD symptoms, response trajectories could be broadly classified into treatment responders and non-responders across both studies. For substance use, response trajectories could be broadly classified into declining, moderately stable, and abstaining profiles. When considering PTSD symptoms and substance use trajectories together, profiles emerged that would have been missed had these treatment outcomes been considered separately.

In the aftermath of mass trauma, posttraumatic stress disorder (PTSD) symptoms follow prototypical trajectories of resilience, recovery, or chronic distress. The coronavirus disease 2019 (COVID-19) pandemic represented an unheralded opportunity to better understand heterogeneous trajectories of PTSD symptoms across a prolonged period of social disruption and stress. We tracked the PTSD symptoms of trauma-exposed individuals in the U.S., sought to identify population-based variability in PTSD symptom trajectories, and understand what, if any, early pandemic experiences would predict their membership in one trajectory over others. As part of a large-scale longitudinal study of U.S. residents during the pandemic, participants who reported at least one potentially traumatic event in their lifetime (N = 1206) at Wave 1 (April 2020) were included in the current study. PTSD symptoms were assessed with the PTSD Checklist for DSM-5 at four time points extending to July 2021. Latent growth mixture modeling was used to identify heterogeneous symptom trajectories. Trajectory membership was regressed on baseline demographics and experiences from the early stage of the pandemic as measured by the Epidemic-Pandemic Impacts Inventory. Four trajectories (Resilient [73%], Recurring [13.3%], Recovering [8.3%], and Chronic [5.5%] were identified. Age, trauma load, and early pandemic experiences (emotional/physical health problems and positive changes) were each significant predictors of trajectory membership. Predictors primarily differentiated the Resilient from each of the other three trajectories. Distinct PTSD symptom trajectories during the COVID-19 pandemic point to the need for targeted efforts helping those at most risk for ongoing distress.

This study examines whether race disparities exist in the prediction of suicide attempts and if have they have detrimental effects on individuals and health care systems

The burden of illness for PTSD is staggering and confers significant interference in work, social functioning, as well as increased risk for other physical and mental health problems. Recently, there's been considerable attention paid to the potential therapeutic use of cannabidiol (CBD) products in the treatment of a variety of physical and mental health problems. The endocannabinoid system (ECS) is a logical therapeutic target for combating PTSD and other fear-based disorders given that cannabinoid receptors and other molecular mediators crucial for ECS signaling are richly expressed in a variety of brain regions that govern the regulation of learned fear and defensive behavior.This is an 8-week single-site Phase II randomized double-blind placebo-controlled fixed dose clinical trial. Participants recruited throughout the United States (N = 150) meeting DSM-5 criteria for posttraumatic stress disorder are randomly assigned to one of three treatment arms: (a) 300 mg CBD Isolate; (b) 300 mg CBD Broad Spectrum; and (c) Placebo oil. The primary outcome is PTSD symptom severity as indexed by the PTSD Checklist for DSM-5 (PCL-5) assessed at post treatment (Week 9) and follow-up (Week 13). Secondary outcomes including patient-rated depression, overall disability, anxiety, quality of life, and alcohol use are assessed weekly throughout the trial. Safety and CBD adherence are assessed daily throughout the trial.This is the first placebo-controlled clinical trial investigating (a) CBD for the treatment of PTSD; and (b) the first study to test the relative efficacy of CBD Isolate vs CBD Broad Spectrum. Trial registration ClinicalTrials.gov registered (12/12/2019), trial identifier NCT04197102.issued 08/04/2022, protocol amendment number #2019-05-0123.

Preclinical experiments with rodents demonstrate that cannabidiol (CBD), the non-psychotomimetic constituent of the Cannabis sativa plant, disrupts reconsolidation of aversive memories conditioned in the laboratory when administered within the memory reconsolidation window (6 h. post-retrieval) by indirectly activating cannabinoid type-1 (CBFor this proof-of-concept, placebo-controlled double-blind trial, volunteers (n = 99) reporting elevated fears of somatic sensations will be stratified on biological sex and randomized to one of three intervention arms: (a). CBD-rich oil administered within the reconsolidation window, (b) Placebo oil administered within the reconsolidation window; or (c) CBD-rich oil administered outside of the reconsolidation window. Change in emotional reactivity to a 35% COStudy findings may contribute towards the development of a novel brief transdiagnostic intervention guided by reconsolidation theory for individuals prone to fear-related psychiatric disorders.ClinicalTrials.gov Identifier: NCT04726475.

Network analysis has been increasingly applied in an effort to understand complex interactions among symptoms in posttraumatic stress disorder (PTSD). Although methods that initially focused on identifying central symptoms in cross-sectional networks have been extended to longitudinal data that can reveal the relative roles of acute symptoms in the emergence of the PTSD syndrome, the association between network metrics and symptom change during treatment have yet to be explored in PTSD. To address this gap, we estimated pretreatment PTSD symptom networks in a sample of patients from a multisite clinical trial for women with full or subthreshold PTSD and substance use. We tested the hypothesis that node metrics calculated in the pretreatment network would be predictive of the strength of the association between a symptom's change and the change in the severity of all other symptoms through the course of treatment. A symptom node's strength and predictability in the pretreatment network were each strongly correlated with the association between that symptom's change and overall change across the symptom network, r(15) = .79, p < .001 and r(15) = .75, p < .001, respectively, whereas a symptom's mean severity at pretreatment was not, r(15) = .27, p = .292. These findings suggest that a node's centrality prior to treatment engagement is a predictor of its association with overall symptom change throughout the treatment process.

The combination of unhealthy alcohol use and depression is associated with adverse outcomes including higher rates of alcohol use disorder and poorer depression course. Therefore, addressing alcohol use among individuals with depression may have a substantial public health impact. We compared the effectiveness of a brief intervention (BI) for unhealthy alcohol use among patients with and without depression.This observational study included 312,056 adult primary care patients at Kaiser Permanente Northern California who screened positive for unhealthy drinking between 2014 and 2017. Approximately half (48%) received a BI for alcohol use and 9% had depression. We examined 12-month changes in heavy drinking days in the previous three months, drinking days per week, drinks per drinking day, and drinks per week. Machine learning was used to estimate BI propensity, follow-up participation, and alcohol outcomes for an augmented inverse probability weighting (AIPW) estimator of the average treatment (BI) effect. This approach does not depend on the strong parametric assumptions of traditional logistic regression, making it more robust to model misspecification.BI had a significant effect on each alcohol use outcome in the non-depressed subgroup (-0.41 to -0.05, all ps .003), but not in the depressed subgroup (-0.33 to -0.01, all ps .28). However, differences between subgroups were nonsignificant (0.00 to 0.11, all ps .44).On average, BI is an effective approach to reducing unhealthy drinking, but more research is necessary to understand its impact on patients with depression. AIPW with machine learning provides a robust method for comparing intervention effectiveness across subgroups.

Assessing the role of cannabinoid (CB) receptors in behavior is relevant given the trend toward the legalization of medicinal and recreational marijuana. The present research aims at bridging a gap in our understanding of CB-receptor function in animal models of frustrative nonreward. These experiments were designed to (1) determine the effects of chronic administration of the nonselective CB1-receptor agonist WIN 55,212-2 (WIN) on reward downshift in rats and (2) determine whether the effects of chronic WIN were reducible to acute effects. In Experiment 1, chronic WIN (7 daily injections, 10 mg/kg, ip) accelerated the recovery of consummatory behavior after a 32-to-4% sucrose downshift relative to vehicle controls. In addition, chronic WIN eliminated the preference for an unshifted lever when the other lever was subject to a 12-to-2 pellet downshift in free-choice trials, but only in animals with previous experience with a sucrose downshift. In Experiment 2, acute WIN (1 mg/kg, ip) reduced consummatory behavior, but did not affect recovery from a 32-to-4% sucrose downshift. The antagonist SR 141716A (3 mg/kg, ip) also failed to interfere with recovery after the sucrose downshift. In Experiment 3, acute WIN administration (1 mg/kg, ip) did not affect free-choice behavior after a pellet downshift, although it reduced lever pressing and increased magazine entries relative to vehicle controls. The effects of chronic WIN on frustrative nonreward were not reducible to acute effects of the drug. Chronic WIN treatment in rats, like chronic marijuana use in humans, seems to increase resistance to the effects of frustrative nonreward.

Adolescent depression is a clinically relevant concern that has major implications for mental and physical health. The trajectory of depressive symptoms among adolescents suggests that there is likely variability throughout this developmental period. The aim of the study was to assess the longitudinal relationship between individual symptoms of depression among early and middle adolescents to provide guidance for future research investigating targeted intervention efforts. Data were extracted from electronic medical records (2015–2017) from a pediatric primary care clinic in an urban setting. Cross-Lagged Panel Network analysis was used to evaluate symptoms of depression measured with the Patient Health Questionnaire (PHQ-9) measured twice over a 1-year period among early adolescents (ages 11–13 years; n = 309) and middle adolescents (ages 14–16 years; n = 255). The sample was predominantly Hispanic (90%) and 56% female. The analyses highlighted key differences and similarities between early and middle adolescence, largely focused on the role of suicidal ideation and tightly linked with feelings of failure and appetitive disturbance. In early adolescence suicidal ideation was highly likely to lead to other symptoms. In middle adolescence, however, suicidal ideation no longer had connections to other symptoms and instead the strongest connections were toward suicidal ideation. Interestingly, across both early and middle adolescence feelings of failure and appetitive disturbance were highly likely to lead to suicidal ideation. These exploratory findings highlight several longitudinal associations between early and middle adolescence that provide insight into differences and similarities regarding how symptoms might progress within those developmental periods. Taken together these results can provide direction for future research to evaluate brief, targeted interventions for adolescents.

Addressing mental health challenges related to the COVID-19 outbreak can be facilitated through research that characterizes the needs of subpopulations and identifies specific pathways to targeted intervention. Toward this aim, we examined the impact of the COVID-19 outbreak on anxiety symptoms among college students (N = 487) and explored the relative impact of coping strategies using a psychological network approach, which models complex interactions to identify potential pathways to symptom-level intervention. Although students showed several significant fluctuations in pre- to post-outbreak anxiety symptom levels measured with the GAD-7, anxiety network connectivity was not significantly different across timepoints. Consistent with hypotheses, the post-outbreak symptom+coping network revealed that increased use of the adaptive coping strategies of acceptance, behavioral activation, and values-based action was associated with lower levels of fear, restlessness, and trouble relaxing. The symptom+coping network also revealed that increased use of the maladaptive strategies of excessive cleaning, reassurance seeking, and excessive checking was associated with higher levels of irritability and fear. Surprisingly, the use of reappraisal and avoidance, two strategies with putatively opposing adaptive value, highly overlapped and showed positive associations with fear and irritability. These symptom+coping associations can guide the assessment and treatment of anxiety in the face of COVID-19.

Stereoscopic 3D gives the viewer the same shape, size, perspective and depth they would experience viewing the real world and could mimic the perceptual threat cues present in real life. This is the first study to investigate whether an immersive stereoscopic 3D video exposure-based treatment would be effective in reducing fear of spiders. Participants with a fear of spiders (N = 77) watched two psychoeducational videos with facts about spiders and phobias. They were then randomized to a treatment condition that watched a single session of a stereoscopic 3D immersive video exposure-based treatment (six 5-minute exposures) delivered through a virtual reality headset or a psychoeducation only control condition that watched a 30-minute neutral video (2D documentary) presented on a computer monitor. Assessments of spider fear (Fear of Spiders Questionnaire [FSQ], Behavioral Approach Task [BAT], & subjective ratings of fear) were completed pre- and post-treatment. Consistent with prediction, the stereoscopic 3D video condition outperformed the control condition in reducing fear of spiders showing a large between-group change effect size on the FSQ (Cohen's d = 0.85) and a medium between-group effect size on the BAT (Cohen's d = 0.47). This provides initial support for stereoscopic 3D video in treating phobias.

Background. The application of psychopathological symptom networks requires reconciliation of the observed cross-sample heterogeneity. We leveraged the largest sample to be used in a PTSD network analysis (N = 28,594) to examine the impact of criteria-based and data-driven sampling approaches on the heterogeneity and interpretability of networks.Methods. Severity and diagnostic criteria identified four overlapping subsamples and cluster analysis identified three distinct data-derived profiles. Networks estimated on each subsample were compared to a respective benchmark network at the symptom-relation level by calculating sensitivity, specificity, correlation, and density of the edges. Negative edges were assessed for Berkson’s bias, a source of error that can be induced by threshold samples on severity.Results. Criteria-based networks showed reduced sensitivity, specificity, and density but edges remained highly correlated and a meaningfully higher proportion of negative edges was not observed relative to the benchmark network of all cases. Among the data-derived profile networks, the Low Severity network had the highest proportion of negative edges not present in the benchmark network of symptomatic cases. The High Severity profile also showed a higher proportion of negative edges, whereas the Medium Severity profile did not. Conclusion. Although networks showed differences, Berkson’s bias did not appear to be a meaningful source of systematic error. These results can guide expectations about the generalizability of symptom networks across samples that vary in their ranges of severity. Future work should continue to explore whether network heterogeneity is reflective of meaningful and interpretable differences in the symptom relations from which they are composed.

OBJECTIVE To advance understanding of the effectiveness of evidence-based treatments for comorbid posttraumatic stress disorder (PTSD) and substance use disorder (SUD), research must provide a more nuanced picture of how substance use affects change in PTSD symptoms over the course of treatments and whether prolonged exposure techniques can be efficacious during active substance use. A data set that included patients with PTSD/subthreshold-PTSD and SUD treated with an exposure-based intervention provided an opportunity to conduct a secondary analysis to test how patients' substance use impacted PTSD change over treatment. METHOD We applied growth models to week-to-week PTSD symptom and substance use changes during treatment and follow-up of a randomized controlled trial of two cognitive-behavioral treatments for PTSD and SUD: Concurrent Treatment of PTSD and SUD Using Prolonged Exposure (COPE) and Relapse Prevention Therapy (RPT). Cross-lagged analyses were used to determine whether prior week substance use impacted subsequent PTSD symptom severity. RESULTS Both treatments evidenced significant reductions in PTSD symptom severity. In the context of continued substance use, results suggest that individuals still benefit from exposure-based treatment. CONCLUSION Results provide evidence that RPT and COPE both led to significant reductions in PTSD, providing further support that exposure-based techniques tailored for SUD can be conducted without jeopardizing PTSD or SUD outcomes. Implications for clinical decision making around treatment selection are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

BACKGROUND: Recent research suggests that posttraumatic stress disorder (PTSD) is associated with altered amygdala and hippocampal resting-state functional connectivity (rsFC). However, less research has examined whether Prolonged Exposure (PE), a first line exposure-based treatment for PTSD, has the potential to alter resting state neural networks. METHODS: Twenty-four patients with PTSD and 26 matched trauma-exposed healthy controls (TEHCs) underwent resting-state functional magnetic resonance imaging (fMRI) at baseline. PTSD patients were scanned a second time after completing 10-session PE in which patients narrated a detailed trauma account (imaginal exposure) and confronted trauma reminders (in vivo exposure) to extinguish trauma-related fear responses. TEHC were scanned again following a 10-week waiting period. Seed regions of interest (ROIs) included centromedial amygdala (CMA), basolateral amygdala (BLA), and the hippocampus. RESULTS: Post- versus pre-treatment comparisons indicated increased rsFC of the BLA and CMA with the orbitofrontal cortex (OFC), and hippocampus-medial prefrontal cortex (mPFC) among patients with PTSD, but not among TEHC participants. CONCLUSIONS: Enhanced amygdala and hippocampus rsFC with prefrontal cortical regions following PE could underlie improved capacity for inhibition and re-evaluation of threat, and heightened memory encoding and retrieval ability, respectively. These findings encourage further investigation of this circuitry as a therapeutic target in PTSD.

A goal of clinical trials is to identify unique baseline characteristics that can inform treatment planning. One such target is emotion dysregulation (ED), which contributes to the maintenance of co-occurring posttraumatic stress disorder (PTSD) and substance use disorder (SUD) and may be a potential moderator of treatment response. We examined the moderating impact of ED severity on treatment outcomes in an urban, socioeconomically disadvantaged, and racially/ethnically diverse sample with complex trauma and severe SUDs. Participants with co-occurring PTSD and SUD (PTSD+SUD) were randomized to Concurrent Treatment with Prolonged Exposure (COPE, n = 39), Relapse Prevention Therapy (RPT, n = 43), or an active monitoring control group (AMCG, n = 28). Baseline ED severity moderated treatment outcomes such that high ED was associated with greater reduction in PTSD severity among those who received COPE relative to RPT and AMCG. In contrast, low ED was associated with greater reduction in substance use among those in RPT relative to COPE and AMCG. Implications for individualizing and optimizing treatment selection for PTSD+SUD are discussed.

Background and objectives Perceptual adaptations that facilitate rapid responses to threats can also lead to false alarms, or the failure to discriminate safe stimuli from signals of threat. We examined the impact of varying degrees of threat on false alarms in the perceptual discrimination of faces along the dimension of emotion (Experiment 1) or identity (Experiment 2). Methods Participants first trained to discriminate between a target and nontarget face. Next, we tested their ability to identify the target in randomized presentations of the target, the nontarget, and nine novel stimuli morphed in 10% increments of similarity from the target to the nontarget. The task was completed under one of three randomized conditions: 1) Ongoing-Threat paired the target with an aversive outcome in both phases; 2) Prior-Threat paired the target with an aversive outcome in the training phase only; and 3) No-Threat paired the target with a neutral outcome in the training phase only. Results In Experiment 1 (N = 90), Ongoing-Threat lowered the false alarm threshold for facial discrimination based on anger intensity compared to Prior-Threat and No-Threat. In Experiment 2 (N = 90), Ongoing-Threat and Prior-Threat each lowered the false alarm threshold for identity-based discrimination compared to No-Threat. Limitations The experiment did not measure generalization of threat responses. Conclusion Associating a facial expression or identity with threat leads to faster but less accurate discrimination of faces with similar features, particularly under conditions of ongoing threat. These experiments provide an avenue for examining the parameters that impact false alarms, which play a key role in anxiety disorders.

Preclinical and clinical data have shown that D-cycloserine (DCS), a partial agonist at the N-methyl-d-aspartate receptor complex, augments the retention of fear extinction in animals and the therapeutic learning from exposure therapy in humans. However, studies with non-clinical human samples in de novo fear conditioning paradigms have demonstrated minimal to no benefit of DCS. The aim of this study was to evaluate the effects of DCS on the retention of extinction learning following de novo fear conditioning in a clinical sample. Eighty-one patients with social anxiety disorder were recruited and underwent a previously validated de novo fear conditioning and extinction paradigm over the course of three days. Of those, only 43 (53%) provided analyzable data. During conditioning on Day 1, participants viewed images of differently colored lamps, two of which were followed by with electric shock (CS+) and a third which was not (CS-). On Day 2, participants were randomly assigned to receive either 50 mg DCS or placebo, administered in a double-blind manner 1 hour prior to extinction training with a single CS+ in a distinct context. Day 3 consisted of tests of extinction recall and renewal. The primary outcome was skin conductance response to conditioned stimuli, and shock expectancy ratings were examined as a secondary outcome. Results showed greater skin conductance and expectancy ratings in response to the CS+ compared to CS- at the end of conditioning. As expected, this difference was no longer present at the end of extinction training, but returned at early recall and renewal phases on Day 3, showing evidence of return of fear. In contrast to hypotheses, DCS had no moderating influence on skin conductance response or expectancy of shock during recall or renewal phases. We did not find evidence of an effect of DCS on the retention of extinction learning in humans in this fear conditioning and extinction paradigm.

Item does not contain fulltext The use of fear conditioning and extinction paradigms to examine intermediate phenotypes of anxiety and stress-related disorders has facilitated the identification of neurobiological mechanisms that underlie specific components of abnormal psychological functioning. Across species, acute pharmacologic manipulation of the endogenous cannabinoid system has provided evidence of its critical role in fear extinction, but the effects of chronic cannabis on extinction are relatively understudied. In rats, chronic cannabinoid administration impairs fear extinction in a drug-free state. Here we examine whether chronic cannabis use is associated with impaired fear extinction in humans. Participants were healthy chronic cannabis users (n = 20) and nonuser controls with minimal lifetime cannabis use (n = 20) matched on age, sex, and race who all screened negative for psychiatric disorders. A 2-day differential fear conditioning paradigm was used to test the hypothesis that chronic cannabis use would be associated with impaired extinction of the skin conductance response. Consistent with hypotheses, chronic cannabis use was associated with reduced within-session extinction of skin conductance response on Day 1 (d = 0.78), and between-session extinction on Day 2 (d = 0.76). Unexpectedly, cannabis use was also associated with reduced subjective differentiation between threat and safety stimuli during conditioning. Replication and translation of findings are necessary to test potential mechanisms directly and examine whether impairments can be reversed pharmacologically or after a period of cannabis abstinence. 8 p.

Background: To test whether an integrated prolonged exposure (PE) approach could address posttraumatic stress disorder (PTSD) symptoms effectively in individuals with co-occurring substance use disorders (SUD), we compared concurrent treatment of PTSD and SUD using PE (COPE) to relapse prevention therapy (RPT) for SUD and an active monitoring control group (AMCG). Methods: We conducted a randomized 12-week trial with participants (n = 110; 64% males; 59% African Americans) who met Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for full or subthreshold PTSD and SUD. Participants were randomly assigned to COPE (n = 39), RPT (n = 43), or AMCG (n = 28). Results: At the end-of-treatment, COPE and RPT demonstrated greater reduction in PTSD symptom severity relative to AMCG (COPE-AMCG = -34.06, p < 0.001; RPT-AMCG = -22.58, p = 0.002). Although the difference between COPE and RPT was not significant in the complete sample, the subset of participants with full (vs. subthreshold) PTSD demonstrated significantly greater reduction of PTSD severity in COPE relative to RPT. Both treatments were superior to AMCG in reducing the days of primary substance use (COPE-AMCG = -0.97, p = 0.01; RPT-AMCG = -2.07, p < 0.001). Relative to COPE, RPT showed significantly more improvement in SUD outcome at end-of-treatment (RPT-COPE = -1.10, p = 0.047). At 3-month follow-up, COPE and RPT maintained their treatment gains and were not significantly different in PTSD severity or days of primary substance use. Conclusion: COPE and RPT reduced PTSD and SUD severity in participants with PTSD + SUD. Findings suggest that among those with full PTSD, COPE improves PTSD symptoms more than a SUD-only treatment. The use of PE for PTSD was associated with significant decreases in PTSD symptoms without worsening of substance use.

Background Neurobiological models of posttraumatic stress disorder (PTSD) implicate fear processing impairments in the maintenance of the disorder. Specific deficits in extinction recall, the retention of learned extinction, have been demonstrated. While deficient extinction recall, and the associated activation pattern of prefrontal and hippocampal regions, distinguishes individuals with PTSD from controls, research has not yet examined changes following treatment. We examined the behavioral and neural correlates of extinction recall before and after cognitive behavioral treatment of PTSD. Methods Fifty-eight participants (30 with PTSD, 28 trauma-exposed matched controls) underwent a 2-day behavioral fear conditioning, extinction, and recall paradigm during functional magnetic resonance imaging (fMRI). The same procedures were repeated 10 weeks later, after PTSD patients had completed prolonged exposure treatment. We analyzed fMRI data from 32 subjects (16 PTSD; 16 controls) and skin conductance response (SCR) data from 33 subjects (16 PTSD; 17 controls). Neural activity during extinction recall, SCR, and PTSD symptoms were compared across groups and over time. Results PTSD patients exhibited pre- to post-treatment reduction in rostral anterior cingulate cortex (rACC) activation during extinction recall, and increase in functional coherence between the rACC and the ventromedial prefrontal cortex (vmPFC) and subgenual anterior cingulate cortex (sgACC). Reduced PTSD symptom severity from pre- to post-treatment was significantly associated with reduced subgenual ACC and parahippocampal activation during this task. SCR during the extinction recall phase did not significantly change with treatment in the PTSD group, but change in SCR was associated with reduction in PTSD symptom severity. Conclusions Prolonged exposure treatment appears to alter neural activation in PTSD patients during recall of fear extinction, and change in extinction recall (measured by SCR) is associated with symptom reduction. We discuss results in the context of neural systems involved in response to affective stimuli., Highlights • Deficient recall of extinguished fear (extinction recall; ER) has been associated with PTSD. • Prolonged exposure (PE) is a first line treatment for PTSD which relies on extinction. • Changes in prefrontal activation and functional connectivity during ER appeared following PE. • Changes in ER following PE corresponded to changes in PTSD severity. • Taken together, these findings suggest normalization of ER deficits in PTSD following PE.

Introduction Smoking is a leading cause of morbidity and mortality in the United States. While most smokers endorse a desire to quit, achieving abstinence is notoriously difficult. Network analysis is a method for understanding the complex relationships of factors that maintain smoking behavior and impact motivation to quit. Methods This study examined self-report prescreen data from treatment-seeking smokers (N = 3913). The number of prior quit attempts and withdrawal symptoms experienced, as well as current smoking behavior and motivation to quit were modeled as interconnected nodes in a network. Two key network metrics were examined: 1) edge weights, which quantify the strength and direction of the associations of interest, and 2) the sum of each node’s edge weights, which quantifies the expected influence of a node on the overall network. Results The withdrawal symptom of craving, r = 0.10, 95% CI [0.07, 0.13] and digestive problems, r = −0.06, 95% CI [−0.09, −0.03], had the strongest positive and negative association with daily cigarettes, respectively. The number of prior quit attempts, r = 0.17, 95% CI [0.14, 0.20], concentration problems, r = −0.04, 95% CI [−0.027, −0.01], showed the strongest positive and negative associations, respectively, with current motivation to quit. Nodes with significant links to current smoking and motivation to quit were also among the most influential in the overall network. Conclusions Findings suggest prior quit experiences and consequences associated with withdrawal symptoms may differentially relate to maintenance of smoking behavior and motivation to quit in treatment-seeking smokers. Interventions targeting key withdrawal symptoms may enhance motivation to quit.

Importance Findings suggest that the efficacy of D-cycloserine (DCS) for enhancing exposure therapy may be strongest when administered after sessions marked by low fear at the conclusion of exposure practice. These findings have prompted investigation of DCS dosing tailored to results of exposure sessions. Objective To compare tailored postsession DCS administration with presession DCS administration, postsession DCS administration, and placebo augmentation of exposure therapy for social anxiety disorder. Design, Setting, and Participants This double-blind randomized clinical trial involved adults with social anxiety disorder enrolled at 3 US university centers. Symptom severity was assessed at baseline, weekly during treatment, and at 1-week and 3-month follow-up. Data analysis was performed from September 2019 to March 2020. Interventions Participants completed a 5-session treatment and received pills commensurate with their condition assignment at sessions 2 through 5, which emphasized exposure practice. Main Outcomes and Measures Symptom severity was evaluated by the Liebowitz Social Anxiety Scale and Social Phobic Disorders-Severity Form as administered by independent evaluators. Results A total of 152 participants were enrolled (mean [SD] age, 29.24 [10.16] years; 84 men [55.26%]). Compared with placebo, presession and postsession conditions showed greater symptom improvement (b = −0.25; 95% CI, −0.37 to −0.13;P Conclusions and Relevance Administration of DCS enhanced exposure therapy for social anxiety disorder when given before or after the exposure session. However, the study failed to achieve the aim to develop a tailored clinical application. Trial Registration ClinicalTrials.gov Identifier:NCT02066792

Contains fulltext : 201960.pdf (Publisher’s version ) (Open Access) Memory bias is a risk factor for depression. In two independent studies, the efficacy of one CBM-Memory session on negative memory bias and depressive symptoms was tested in vulnerable samples. We compared positive to neutral (control) CBM-Memory trainings in highly-ruminating individuals (N=101) and individuals with elevated depressive symptoms (N=100). In both studies, participants studied positive, neutral, and negative Swahili words paired with their translations. In five study-test blocks, they were then prompted to retrieve either only the positive or neutral translations. Immediately following the training and one week later, we tested cued recall of all translations and autobiographical memory bias; and also measured mood, depressive symptoms, and rumination. Retrieval practice resulted in training-congruent recall both immediately after and one week after the training. Overall, there was no differential decrease in symptoms or difference in autobiographical memory bias between the training conditions. In the dysphoric but not in the high-ruminating sample, the positive training resulted in positive autobiographical bias only in dysphoric individuals with positive pre-existing bias. We conclude that one session of positive retrieval-based CBM-Memory may not be enough to yield symptom change and affect autobiographical memory bias in vulnerable individuals. 17 p.

Background Maladaptive stress reactivity is a vulnerability factor for the recurrence of mood and anxiety episodes. Since appraisals of situational demand and available resources to cope with a stressor drive stress reactivity, they are meaningful targets for intervention. In the present study, we test whether exercise (EX) can facilitate learning arousal reappraisal (AR) techniques among individuals vulnerable to depressive episodes and thereby improve reactivity to stressful events. Methods Participants (N = 167) with mild-to-moderate symptoms of depression were randomly assigned to inactive control (CTRL), EX (three 5-min bouts at varying intensity), AR instruction, or their combination (EX+AR) prior to undergoing a stressor. Stress appraisal (pre- and post-stressor) and perceived stress (pre-, post-, 5-, 10-, and 15-min post-stressor) were assessed. Results The EX+AR condition reported a more adaptive appraisal of the stressor and exhibited a greater decline in perceived stress immediately and 15-min post the stressor compared to EX and CTRL conditions. The AR condition also reported a more adaptive appraisal of the stressor and exhibited a greater decline in perceived stress but only 15-min after the stressor and only in comparison to the CTRL condition. There were no significant differences between the EX+AR and AR conditions nor between the EX and CTRL conditions. Conclusions Results provide no clear evidence for a synergistic effect for EX+AR and highlights that AR instruction aids adaptive reappraisal of stress. Studies with longitudinal designs are needed. These observations add to the body of literature exploring mechanisms for improving stress reactivity and the role exercise may play.

In this placebo-controlled randomized clinical trial, we examined the efficacy of 250 mg d-cycloserine (DCS) for enhancing the effects of cognitive behavior therapy targeting anxiety sensitivity reduction in the context of smoking cessation treatment among adults with a history of panic attacks. We hypothesized that DCS would enhance treatment of our mechanistic targets-anxiety sensitivity and panic and related symptoms-and result in greater smoking abstinence. A total of 53 smokers were randomized to a 7-week integrated treatment and received study medication (DCS or placebo) prior to sessions 3-5; these sessions emphasized interoceptive exposure practice. Nicotine replacement therapy was initiated at session 5 (quit date). We found that DCS augmentation led to greater reductions of one (anxiety sensitivity) of two of our mechanistic targets at early but not late assessments, and that engaging that target predicted better smoking outcomes. However, there was no evidence of group (DCS vs. placebo) differences in smoking cessation success at treatment endpoint or follow-up evaluations. Hence, although we found that DCS can enhance treatment targeting a smoking maintaining factor, additional strategies appear to be needed to significantly affect smoking outcomes.

BackgroundRandomized control trials (RCTs) comparing attention control training (ACT) and attention bias modification (ABM) in posttraumatic stress disorder (PTSD) have shown mixed results. The current RCT extends the extant literature by comparing the efficacy of ACT and a novel bias-contingent-ABM (BC-ABM), in which direction of training is contingent upon the direction of pre-treatment attention bias (AB), in a sample of civilian patients with PTSD.MethodsFifty treatment-seeking civilian patients with PTSD were randomly assigned to either ACT or BC-ABM. Clinician and self-report measures of PTSD and depression, as well as AB and attention bias variability (ABV), were acquired pre- and post-treatment.ResultsACT yielded greater reductions in PTSD and depressive symptoms on both clinician-rated and self-reported measures compared with BC-ABM. The BC-ABM condition successfully shifted ABs in the intended training direction. In the ACT group, there was no significant change in ABV or AB from pre- to post-treatment.ConclusionsThe current RCT extends previous results in being the first to apply ABM that is contingent upon AB at pre-treatment. This personalized BC-ABM approach is associated with significant reductions in symptoms. However, ACT produces even greater reductions, thereby emerging as a promising treatment for PTSD.

Posttraumatic stress disorder (PTSD) develops in a substantial minority of emergency room admits. Inexpensive and accurate person-level assessment of PTSD risk after trauma exposure is a critical precursor to large-scale deployment of early interventions that may reduce individual suffering and societal costs. Toward this aim, we applied ensemble machine learning to predict PTSD screening status three months after severe injury using cost-effective and minimally invasive data. Participants (N = 271) were recruited at a Level 1 Trauma Center where they provided variables routinely collected at the hospital, including pulse, injury severity, and demographics, as well as psychological variables, including self-reported current depression, psychiatric history, and social support. Participant zip codes were used to extract contextual variables including population total and density, average annual income, and health insurance coverage rates from publicly available U.S. Census data. Machine learning yielded good prediction of PTSD screening status 3 months post-hospitalization, AUC = 0.85 95% CI [0.83, 0.86], and significantly outperformed all benchmark comparison models in a cross-validation procedure designed to yield an unbiased estimate of performance. These results demonstrate that good prediction can be attained from variables that individually have relatively weak predictive value, pointing to the promise of ensemble machine learning approaches that do not rely on strong isolated risk factors.

BACKGROUND: Brain structures underlying posttraumatic stress disorder (PTSD) have been a focus of imaging studies, but associations between treatment outcome and alterations in brain structures remain largely unexamined. We longitudinally examined the relation of structural changes in the rostral anterior cingulate cortex (rACC), a previously identified key region in the PTSD fear network, to outcome of prolonged exposure (PE) treatment. METHOD: The sample included 78 adults (53 women): 41 patients with PTSD and 37 trauma-exposed healthy volunteers (TE-HCs). Patients underwent a 10-week course of PE treatment and completed pre- and posttreatment assessments and magnetic resonance imaging (MRI) structural scans. TE-HCs also underwent assessment and MRI at baseline and 10 weeks later. PE remitters (n = 11), nonremitters (n = 14), and TE-HCs, were compared at baseline on demographic and clinical characteristics and ACC structure. Remitters, nonremitters, and TE-HCs were compared for pre- to posttreatment clinical and structural ACC change, controlling for potential confounding variables. RESULTS: There were no baseline differences in structure between PTSD and TE-HCs or remitters and nonremitters. Following treatment, PTSD remitters exhibited cortical thinning and volume decrease in the left rACC compared with PTSD nonremitters and TE-HCs. CONCLUSIONS: These results, while in need of replication, suggest that PE treatment for PTSD, by extinguishing maladaptive trauma associations, may promote synaptic plasticity and structure change in rACC. Future research should explore possible underlying mechanisms. Language: en

Introduction and Aims Despite advances towards integration of care for women with co-occurring substance use disorder (SUD) and post-traumatic stress disorder (PTSD), low abstinence rates following SUD/PTSD treatment remain the norm. The utility of investigating distinct substance use trajectories is a critical innovation in the detection and refining of effective interventions for this clinical population. Design and Methods The present study reanalysed data from the largest randomised clinical trial to date for co-occurring SUD and PTSD in women (National Drug Abuse Treatment Clinical Trials Network; Women and Trauma Study). Randomised participants (n = 353) received one of two interventions in addition to treatment as usual for SUD: (i) trauma-informed integrative treatment for PTSD/SUD; or (ii) an active control psychoeducation course on women's health. The present study utilised latent growth mixture models (LGMM) with multiple groups to estimate women's substance use patterns during the 12-month follow-up period. Results Findings provided support for three different trajectories of substance use in the post-treatment year: (i) consistently low likelihood and use frequency; (ii) consistently high likelihood and use frequency; and (iii) high likelihood and moderate use frequency. Covariate analyses revealed improvement in PTSD severity was associated with membership in a specific substance use trajectory, although receiving trauma-informed treatment was not. Additionally, SUD severity, age and after-care efforts were shown to be related to trajectory membership. Discussion and Conclusions Findings highlight the necessity of accounting for heterogeneity in post-treatment substance use, relevance of trauma-informed care in SUD recovery and benefits of incorporating methodologies like LGMM when evaluating SUD treatment outcomes. [Lopez-Castro T, Hu M-C, Papini S, Ruglass LM, Hien DA. Pathways to change: Use trajectories following trauma-informed treatment of women with co-occurring post-traumatic stress disorder and substance use disorders. Drug Alcohol Rev 2015]

Despite the lack of clinical research, marijuana and synthetic cannabinoids have been approved to treat posttraumatic stress disorder (PTSD) in several states in the United States. This review critically examines preclinical research on the endocannabinoid system (ECS) in order to evaluate three key questions that are relevant to PTSD: (1) Does ECS dysfunction impact fear extinction? (2) Can stress-related symptoms be prevented by ECS modulation? (3) Is the ECS a potential target for enhancing PTSD treatment? Disruption of the ECS impaired fear extinction in rodents, and ECS abnormalities have been observed in PTSD. Targeting fear memories via the ECS had mixed results in rodents, whereas augmented cannabinoid receptor activation typically facilitated extinction. However, the translational value of these findings is limited by the paucity and inconsistency of human research. Further investigation is necessary to determine whether incorporating cannabinoids in treatment would benefit individuals with PTSD, with cautious attention to risks.

Background Exposure therapy is an established learning-based intervention for the treatment of anxiety disorders with an average response rate of nearly 50%, leaving room for improvement. Emerging strategies to enhance exposure therapy in humans and fear extinction retention in animal models are primarily pharmacological. These approaches are limited as many patients report preferring non-pharmacological approaches in therapy. With general cognitive enhancement effects, exercise has emerged as a plausible non-pharmacological augmentation strategy. The present study tested the hypothesis that fear extinction and exposure therapy would be enhanced by a pre-training bout of exercise. Methods We conducted four experiments with rats that involved a standardized conditioning and extinction paradigm and a manipulation of exercise. In a fifth experiment, we manipulated vigorous-intensity exercise prior to a standardized virtual reality exposure therapy session among adults with fear of heights. Results In experiments 1–4, exercise did not facilitate fear extinction, long-term memory, or fear relapse tests. In experiment 5, human participants showed an overall reduction in fear of heights but exercise did not enhance symptom improvement. Conclusions Although acute exercise prior to fear extinction or exposure therapy, as operationalized in the present 5 studies, did not enhance outcomes, these results must be interpreted within the context of a broader literature that includes positive findings. Taken all together, this suggests that more research is necessary to identify optimal parameters and key individual differences so that exercise can be implemented successfully to treat anxiety disorders.

In humans and other mammals, the unexpected loss of a resource can lead to emotional conflict. Consummatory successive negative contrast (cSNC) is a laboratory model of reward devaluation meant to capture that conflict. In this paradigm, animals are exposed to a sharp reduction in the sucrose concentration of a solution after several days of access. This downshift in sucrose content leads to behavioral responses such as the suppression of consumption and physiologic responses including elevation of corticosterone levels. However, response heterogeneity in cSNC has yet to be explored and may be relevant for increasing the validity of this model, as humans demonstrate clinically meaningful heterogeneity in response to resource loss. The current analysis applied latent growth mixture modeling to test for and characterize heterogeneity in recovery from cSNC among rats (N=262). Although most animals exhibited recovery of consummatory behavior after a sharp drop in consumption in the first postshift trial (Recovery class; 83%), two additional classes were identified including animals that did not change their consumption levels after downshift (No Contrast class; 6%), and animals that exhibited an initial response similar to that of the Recovery class but did not recover to preshift consumption levels (No Recovery class; 11%). These results indicate heterogeneity in recovery from reward loss among rats, which may increase the translatability of this animal model to understand diverse responses to loss among humans.

Background: Background: Research has demonstrated a strong link between trauma, posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) in general and cannabis use disorders in particular. Yet, few studies have examined the impact of cannabis use on treatment outcomes for individuals with co-occurring PTSD and SUDs. Methods: Participants were 136 individuals who received cognitive-behavioral therapies for co-occurring PTSD and SUD. Multivariate regressions were utilized to examine the associations between baseline cannabis use and end-of-treatment outcomes. Multilevel linear growth models were fit to the data to examine the cross-lagged associations between weekly cannabis use and weekly PTSD symptom severity and primary substance use during treatment. Results: There were no significant positive nor negative associations between baseline cannabis use and end-of-treatment PTSD symptom severity and days of primary substance use. Cross-lagged models revealed that as cannabis use increased, subsequent primary substance use decreased and vice versa. Moreover, results revealed a crossover lagged effect, whereby higher cannabis use was associated with greater PTSD symptom severity early in treatment, but lower weekly PTSD symptom severity later in treatment. Conclusion: Cannabis use was not associated with adverse outcomes in end-of-treatment PTSD and primary substance use, suggesting independent pathways of change. The theoretical and clinical implications of the reciprocal associations between weekly cannabis use and subsequent PTSD and primary substance use symptoms during treatment are discussed.

Item does not contain fulltext Background: While important for substance use outcomes, knowledge about treatment attendance patterns, and their relation with clinical outcomes is limited. We examined the association between attendance patterns and smoking outcomes in a randomized, controlled smoking cessation intervention trial. Methods: In addition to standard smoking cessation treatment, participants were randomized to 15 weeks of an exercise intervention (n = 72) or an education control condition (n = 64). Latent class growth analysis (LCGA) tested whether intervention attendance would be better modeled as qualitatively distinct attendance patterns rather than as a single mean pattern. Multivariate generalized linear mixed modeling (GLMM) was used to evaluate associations between the attendance patterns and abstinence at the end of treatment and at 6-month follow-up. Results: The LCGA solution with three patterns characterized by high probability of attendance throughout (Completers, 46.3%), gradual decreasing probability of attendance (Titrators, 23.5%), and high probability of dropout within the first few weeks (Droppers, 30.1%) provided the best fit. The GLMM analysis indicated an interaction of attendance pattern by treatment condition, such that titration was associated with lower probability of quit success for those in the control condition. Probability of quit success was not significantly different between Titrators and Completers in the exercise condition. Conclusions: These findings underscore the importance of examining how treatment efficacy may vary as a function of attendance patterns. Importantly, treatment discontinuation is not necessarily indicative of poorer abstinence outcome. 5 p.

Item does not contain fulltext This manuscript details a randomized controlled study designed to test the efficacy of power posing (i.e., briefly holding postures associated with dominance and power) as an augmentative strategy for exposure therapy for social anxiety disorder (SAD). Seventy-three individuals diagnosed with SAD were assigned to one of three conditions: power posing, submissive posing, or rest (no posing) prior to participating in an exposure therapy session. Participants were assessed for between-group differences in pre- and post-manipulation salivary hormone levels, within-session subjective experiences of fear, and pre- and 1-week post-treatment SAD severity outcome measures. Though the intervention resulted in decreased SAD symptom severity one week later, analyses revealed no significant between-group differences on any tested variables. Accordingly, this study provides no evidence to suggest that power posing impacts hormone levels or exposure therapy outcomes. 7 p.

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Background Individuals with comorbid posttraumatic stress disorder and major depressive disorder (PTSD-MDD) often exhibit greater functional impairment and poorer treatment response than individuals with PTSD alone. Research has not determined whether PTSD-MDD is associated with different network connectivity abnormalities than PTSD alone. Methods We used functional magnetic resonance imaging (fMRI) to measure resting state functional connectivity (rs-FC) patterns of brain regions involved in fear and reward processing in three groups: patients with PTSD-alone (n = 27), PTSD-MDD (n = 21), and trauma-exposed healthy controls (TEHCs, n = 34). Based on previous research, seeds included basolateral amygdala (BLA), centromedial amygdala (CMA), and nucleus accumbens (NAcc). Results Regardless of MDD comorbidity, PTSD was associated with decreased connectivity of BLA-orbitalfrontal cortex (OFC) and CMA-thalamus pathways, key to fear processing, and fear expression, respectively. PTSD-MDD, compared to PTSD-alone and TEHC, was associated with decreased connectivity across multiple amygdala and striatal-subcortical pathways: BLA-OFC, NAcc-thalamus, and NAcc-hippocampus. Further, while both the BLA-OFC and the NAcc-thalamus pathways were correlated with MDD symptoms, PTSD symptoms correlated with the amygdala pathways (BLA-OFC; CMA-thalamus) only. Conclusions Comorbid PTSD-MDD may be associated with multifaceted functional connectivity alterations in both fear and reward systems. Clinical implications are discussed.

Deficits in fear extinction learning are hypothesized to underlie the development of posttraumatic stress disorder (PTSD). Such deficits may, in part, be due to genetic and epigenetic variation in the stress related gene FKBP5. Conversely, altering FKBP5 epigenetic responses during memory consolidation may rescue extinction deficits making it a target for acute intervention to prevent the development of PTSD. Study 1 (Humans) examines if FKBP5 single nucleotide polymorphisms (SNPs) and PTSD symptom domains (re-experiencing, avoidance/numbing, hyperarousal) are associated with abnormal fear extinction phenotypes identified using latent growth mixture modeling (LGMM). Study 2 (Mice) tests if increasing doses of dexamethasone administered prior to extinction alters Fkbp5 mRNA production in the amygdala after extinction and recall and prevents the development of abnormal extinction phenotypes. In humans, abnormal extinction was associated with the TT homozygous genotype of FKBP5 SNPs RS9470080 and RS1360780, and hyperarousal symptoms. In mice, dexamethasone 300 μg/kg was associated with increased amygdala Fkbp5 mRNA following extinction and robust extinction learning while lower doses were not associated with amygdala Fkbp5 mRNA or differences in extinction learning. Further, mice that extinguished on dexamethasone 300 μg/kg maintained low levels of freezing behavior during recall training while mRNA levels were no longer elevated. Together, findings indicate that FKBP5 confers risk for fear extinction deficits. However, this risk may be ameliorated by increasing fkbp5 mRNA expression in the amygdala during memory consolidation making this mechanism a plausible point of acute intervention to prevent the development of PTSD.