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Posttraumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. The most commonly recommended first-line treatments for PTSD among adults are individual trauma-focused psychotherapies. Other evidence-based treatments include specific antidepressant medications and non-trauma-focused psychotherapies. Despite the effectiveness of these available treatments, many patients' symptoms do not remit. This has led to the search for novel treatments for PTSD. In this review, the authors critically evaluate the data supporting several emerging pharmacological and other somatic interventions in the categories of medication-assisted psychotherapy, novel medication monotherapy strategies, and neuromodulation, selected because of the salience of their mechanisms of action to the pathophysiology of PTSD (e.g., MDMA-assisted psychotherapy, ketamine, cannabidiol, transcranial magnetic stimulation). The authors also evaluate the evidence for treatments that are the focus of increasing scientific or public interest (i.e., hyperbaric oxygen therapy, stellate ganglion block, neurofeedback). To date, the evidence supporting most novel pharmacological and somatic treatments for PTSD is preliminary and highly variable; however, the data for several specific treatments, such as transcranial magnetic stimulation, are encouraging., Competing Interests: Dr. Kelmendi is a Co-founder, consultant, and has equity in Transcend Therapeutics, and is also a consultant for Ceruvia Lifesciences. Dr. Alpert reports royalties from Cambridge University Press, Honoraria from Belvoir Publishing and MGH Psychiatry Academy. Dr. Carpenter discloses consulting income in the past three years from Neuronetics, Neurolief, Magnus Medical, Motif Neurotech, Sage Therapeutics, Otsuka, MAPS Public Benefit Corporation, and Change Healthcare. She has clinical trials contracts with Neuronetics, Neurolief, and Janssen and research device loans from Neuronetics and Nexstim. Her effort was supported in part by the National Institute of General Medical Sciences (P20GM130452) funded COBRE Center for Neuromodulation at Butler Hospital. Dr. Grzenda discloses income from consulting to the American Psychiatric Association. Dr. Kraguljac has served on an advisory board for Neurocrine Biosciences Inc. and is a member of the American Board of Psychiatry and Neurology Article Based Continuing Certification committee. Dr. McDonald is compensated as the chair of the DSMB for an NIA sponsored multicenter study. He is on the Board of Skyland Trail and 3Keys. He is a paid consultant for Signant and Sage Therapeutics. He receives a stipend as a deputy editor of the American Journal of Psychiatry. Dr. Rodriguez has, in the last three years, been a consultant for Biohaven Inc., Osmind, and Biogen; received research grant support from Biohaven Inc.; received royalties from American Psychiatric Association Publishing; and received a stipend from APA Publishing for her role as Deputy Editor at The American Journal of Psychiatry. Dr. Rodriguez’s effort was supported in part by the VA Office of Research and Development Clinical Science Research & Development Service, US, Department of Veterans Affairs (1I01CX001789-01A2). Dr. Widge discloses device donations from Medtronic, consulting income from Dandelion Science, and multiple unlicensed patents in the area of brain stimulation for psychiatric illness. Dr. Nemeroff serves as a paid consultant to AbbVie, ANeuroTech (division of Anima BV), Signant Health, Magstim, Inc., Intra-Cellular Therapies, Inc., EMA Wellness, Sage, Silo Pharma, Engrail Therapeutics, Pasithea Therapeutic Corp., EcoR1, GoodCap Pharmaceuticals, Inc., Senseye, Clexio, Ninnion Therapeutics, AncoraBio, and SynapseBio. Dr. Nemeroff is a stockholder with the following: Seattle Genetics, Antares, Inc., Corcept Therapeutics Pharmaceuticals Company, EMA Wellness, and Naki Health. He serves on the scientific advisory boards of ANeuroTech (division of Anima BV), Brain and Behavior Research Foundation (BBRF), Anxiety and Depression Association of America (ADAA), Skyland Trail, Signant Health, Laureate Institute for Brain Research (LIBR), Inc., Heading Health, Pasithea Therapeutic Corp., and Sage and on the board of directors for Gratitude America, ADAA, Lucy Scientific Discovery, Inc. His patents are as follows: “Method and devices for transdermal delivery of lithium (US 6,375,990B1)” and “Method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (US 7,148,027B2).” Dr. Holtzheimer receives royalties from Oxford University Press and UpToDate. Drs. Sippel, Hamblen, and Schnurr report no financial relationships with commercial interests.

Background: Leveraging military veterans' intimate relationships during treatment has the potential to concurrently improve posttraumatic stress disorder (PTSD) symptoms and relationship quality. Cognitive-Behavioral Conjoint Therapy (CBCT) and an 8-session Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) are manualized treatments designed to simultaneously improve PTSD and relationship functioning for couples in which one partner has PTSD. Although efficacious in improving PTSD, the effects of CBCT on relationship satisfaction are small, especially among veterans. Intranasal oxytocin, which targets mechanisms of PTSD and relationship quality, may enhance the efficacy of bCBCT., Method/design: The purpose of this 4-year clinical trial is to compare the outcomes of bCBCT augmented with intranasal oxytocin versus bCBCT plus placebo. We will also explore potential mechanisms of action: self-reported communication skills, empathy, and trust. We will recruit 120 dyads (i.e., veteran with PTSD and their intimate partner) from the VA San Diego Healthcare System. Veterans will be administered 40 international units of oxytocin (n = 60) or placebo (n = 60) 30 min before each of 8 bCBCT sessions delivered via telehealth. Clinical and functioning outcomes will be assessed at five timepoints (baseline, mid-treatment, post-treatment, and 3- and 6-month follow-up)., Conclusion: Study findings will reveal the efficacy of oxytocin-assisted brief couple therapy for PTSD, which could serve as highly scalable option for couples coping with PTSD, as well as provide preliminary evidence of interpersonal mechanisms of change., Clinicaltrials: govIdentifier:NCT06194851., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors receive royalties from Gilford Press (Candice M. Monson)., (Copyright © 2024. Published by Elsevier Inc.)

Although the association between post-traumatic stress disorder (PTSD) and social support is well documented, few studies have tested the causal pathways explaining this association at several points in the acute post-trauma recovery period or examined whether the association varies for different sources of social support. To address these gaps, 151 community individuals (mean age = 37.20 years, 69.5% women) exposed to trauma within the previous 6 months were recruited to complete measures of PTSD and social support from intimate partners, friends, and relatives four times in 1 year. In line with recent recommendations for research on social support and PTSD symptoms, random intercept cross-lagged panel modeling (RI-CLPM) was used to examine dynamic changes between PTSD severity and social support over time. The pattern of RI-CLPM cross-lagged coefficients indicated that positive deviations from one's expected stable level of total social support (across all sources) sped up the recovery of PTSD symptoms at the end of the post-trauma year, and more severe PTSD symptoms than expected based on one's expected stable level of PTSD started eroding social support midway through the assessment year. When specific sources of social support were analyzed separately, the association between within-person increases in social support from friends at any given time point accelerated the recovery from PTSD across the entire year. Among participants with intimate partners ( n = 53), intimate partner support did not predict PTSD symptoms, but more severe PTSD symptoms at any given time point predicted less support at the following time point. Results from this longitudinal study provide additional support for the bidirectional relationship between PTSD and social support over time and suggest that perceived social support from friends may be especially helpful during trauma recovery.

Background: Sustaining evidence-based practices (EBPs) is crucial to ensuring care quality and addressing health disparities. Approaches to identifying factors related to sustainability are critically needed. One such approach is Matrixed Multiple Case Study (MMCS), which identifies factors and their combinations that influence implementation. We applied MMCS to identify factors related to the sustainability of the evidence-based Collaborative Chronic Care Model (CCM) at nine Department of Veterans Affairs (VA) outpatient mental health clinics, 3-4 years after implementation support had concluded., Methods: We conducted a directed content analysis of 30 provider interviews, using 6 CCM elements and 4 Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) domains as codes. Based on CCM code summaries, we designated each site as high/medium/low sustainability. We used i-PARIHS code summaries to identify relevant factors for each site, the extent of their presence, and the type of influence they had on sustainability (enabling/neutral/hindering/unclear). We organized these data into a sortable matrix and assessed sustainability-related cross-site trends., Results: CCM sustainability status was distributed among the sites, with three sites each being high, medium, and low. Twenty-five factors were identified from the i-PARIHS code summaries, of which 3 exhibited strong trends by sustainability status (relevant i-PARIHS domain in square brackets): "Collaborativeness/Teamwork [Recipients]," "Staff/Leadership turnover [Recipients]," and "Having a consistent/strong internal facilitator [Facilitation]" during and after active implementation. At most high-sustainability sites only, (i) "Having a knowledgeable/helpful external facilitator [Facilitation]" was variably present and enabled sustainability when present, while (ii) "Clarity about what CCM comprises [Innovation]," "Interdisciplinary coordination [Recipients]," and "Adequate clinic space for CCM team members [Context]" were somewhat or less present with mixed influences on sustainability., Conclusions: MMCS revealed that CCM sustainability in VA outpatient mental health clinics may be related most strongly to provider collaboration, knowledge retention during staff/leadership transitions, and availability of skilled internal facilitators. These findings have informed a subsequent CCM implementation trial that prospectively examines whether enhancing the above-mentioned factors within implementation facilitation improves sustainability. MMCS is a systematic approach to multi-site examination that can be used to investigate sustainability-related factors applicable to other EBPs and across multiple contexts., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The pretreatment quality of intimate relationships can promote or interfere with couple therapy for posttraumatic stress disorder (PTSD) treatment response. We tested whether baseline relationship satisfaction predicted clinical and process outcomes in two dyadic treatments for PTSD. Using data from a randomized trial comparing brief cognitive behavioral conjoint therapy (bCBCT) for PTSD to PTSD family education (PFE) among 137 military veterans and their partners (N = 274, M age = 42.3 years, 46.7% White, 81.0% male veteran partner), we examined whether baseline relationship satisfaction (Couples Satisfaction Index; CSI-32) predicted change in PTSD symptom severity (Clinician Administered PTSD Scale for DSM-5; CAPS-5), psychosocial functioning (Brief Inventory of Psychosocial Functioning; B-IPF), and relationship satisfaction at posttreatment and 6-month follow-up. We also explored associations with process outcomes (working alliance, treatment satisfaction, dropout). In both treatment conditions, neither partner's baseline CSI-32 score moderated change in veteran CAPS-5 or B-IPF score or any process variable. However, baseline CSI-32 scores moderated both partners' CSI-32 score change during bCBCT and PFE; participants who scored in the distressed range at baseline (n = 123) experienced significant improvements in relationship satisfaction, β = .199, whereas there was no change among those in the nondistressed range at baseline (n = 151), β = .025. Results suggest bCBCT and PFE are effective in improving PTSD symptoms and psychosocial functioning regardless of whether a couple is experiencing clinically significant relationship distress; further, these treatments improve relationship satisfaction for the most distressed individuals., (© 2023 International Society for Traumatic Stress Studies.)

Objective: The long-term effectiveness of Department of Veterans Affairs (VA) residential treatment for posttraumatic stress disorder (PTSD), and how it may vary for men and women veterans, is unknown. This is the first national investigation of symptom change from admission, discharge, 4 months, and 1-year postdischarge from VA PTSD residential rehabilitation treatment programs (RRTPs)., Method: Participants included all veterans discharged from 40 VA PTSD RRTPs October 1, 2017-September 30, 2020 ( n = 2,937; 14.3% women). Linear mixed models examined PTSD and depressive symptoms across time points; it was hypothesized that women veterans would experience greater symptom reduction during and after treatment., Results: Overall, veterans reported large-sized reductions of PTSD symptoms at all time points (Cohen's d : discharge = 1.23, 4-month follow-up d = 0.97, 1-year follow-up d = 1.51). Treatment effects for depressive symptoms were large-sized at all time points (Cohen's d ; discharge = 1.03, 4-month follow-up d = 0.94, 1-year follow-up d = 1.05). Women veterans showed greater improvement in PTSD and depressive symptom severity ( p < .001) than men at discharge, but not at 4-month or 1-year follow-ups., Conclusions: Veterans reported significant reductions in PTSD and depressive symptoms, and treatment gains were maintained one year postdischarge. Women experienced greater benefit during, but not after, treatment. Results not only provide support for the effectiveness of VA residential treatment for PTSD but also highlight the continued need for strategies to maximize and maintain treatment gains. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Cognitive Processing Therapy (CPT) and Prolonged Exposure (PE) are first-line treatments for posttraumatic stress disorder (PTSD). There have been few direct comparisons of CPT and PE intended to determine their comparative effectiveness, none of which have examined outcomes among military veterans receiving these treatments in a residential setting such as the Department of Veterans Affairs (VA) residential rehabilitation treatment programs (RRTPs). Such work is essential given that these veterans are among the most complex and severely symptomatic patients with PTSD treated in VA. In this study we compared changes in PTSD and depressive symptoms across admission, discharge, four months and 12 months following discharge among veterans who received CPT or PE within VA RRTPs., Methods: Using linear mixed models conducted on program evaluation data derived from the electronic medical record and follow-up surveys, we compared self-reported PTSD and depressive symptom outcomes among 1130 veterans with PTSD who were treated with individual CPT ( n = 832, 73.5%) or PE ( n = 297, 26.5%) in VA PTSD RRTPs in fiscal years 2018-2020., Results: PTSD and depressive symptom severity did not significantly differ at any time points. The CPT and PE groups both showed large-sized reductions in PTSD (CPT d = 1.41, PE d = 1.51) and depression (CPT d = 1.01, PE d = 1.09) from baseline to 12-month follow-up., Conclusions: Outcomes for PE and CPT do not differ among a highly complex population of veterans with severe PTSD and several comorbid conditions that can make it difficult to engage in treatment.

Interpersonal functioning is a common concern for people with postttraumatic stress disorder (PTSD) but is not a key target of most trauma-focused psychotherapies (TFPs). We preregistered and undertook a systematic review and meta-analysis of randomized clinical trials (RCTs) examining the efficacy of TFPs for improving interpersonal functioning. Studies were identified through the PTSD Trials Standardized Data Repository, scholarly databases, and the solicitation of unpublished data from the PTSD research community following current PRISMA guidelines. We used random effects meta-analysis to estimate within-group change (i.e., pre- to posttreatment) in interpersonal functioning. Meta-analytic findings yielded a medium total effect of TFP on interpersonal functioning, g = 0.54, 95% CI [0.37, 0.72], with high between-study heterogeneity. Sensitivity analyses yielded substantively equivalent point estimates when outliers were excluded, g = 0.55, and when only the most well-established individual TFPs were included, g = 0.57. In contrast, allocation to a control condition was associated with little average change in interpersonal functioning, g = 0.04 [-0.12, 0.21]. Formal tests did not yield clear evidence of publication bias. Bias-corrected estimates varied but centered around a medium effect, gs = 0.41-1.11. There was a medium-to-large association between change in interpersonal functioning and change in PTSD symptoms, rs = -.35--.44. The extant literature on TFPs and interpersonal functioning is small and heterogeneous, indicating the need for more focused attention on this outcome. Results suggest that, on average, TFPs are moderately efficacious for improving interpersonal functioning; however, additional treatment may be needed to meet the desired level of improvement., (© 2023 International Society for Traumatic Stress Studies.)

Posttraumatic stress disorder (PTSD) negatively impacts military veterans and their intimate partners. Cognitive-Behavioral Conjoint Therapy (CBCT) was developed to address both PTSD and relationship satisfaction among couples. Although efficacious in improving PTSD, the effects of CBCT and the 8-session brief CBCT (bCBCT) on relationship satisfaction among veteran patients with PTSD are modest. Pharmacological augmentation with the neuropeptide oxytocin is promising for enhancing bCBCT's potency due to its effects on mechanisms of trauma recovery (e.g., extinction learning) and relationship functioning (e.g., trust, communication). The goal of this pilot uncontrolled clinical trial was to examine the feasibility and preliminary efficacy of bCBCT augmented with intranasal oxytocin for improving PTSD and relationship satisfaction among 10 U.S. veterans with PTSD and their intimate partners. Veterans self-administered 40 international units of intranasal oxytocin 30 min before each bCBCT session delivered to the couple via telehealth. Both partners completed pre-assessment, weekly, post, and 3-month follow-up assessments of PTSD symptoms and relationship satisfaction. Couples also provided qualitative feedback related to feasibility and engagement. Nine dyads completed the treatment. There were no serious adverse events. Veterans and partners reported moderate to large effect size improvements in relationship satisfaction (Hedge's g = 0.55 and 1.01, respectively). Veterans reported large effect size reductions in PTSD severity (Hedge's g = 1.87). These results suggest that virtual oxytocin-assisted bCBCT is feasible, scalable, potentially efficacious, and should be tested with a placebo-controlled randomized controlled trial., (Published by Elsevier Ltd.)

Importance: People with serious mental illness (SMI), defined as a diagnosis of schizophrenia spectrum disorder, bipolar disorder, or disabling major depressive disorder) die approximately 10 to 25 years earlier than the general population., Objective: To develop the first-ever lived experience-led research agenda to address early mortality in people with SMI., Evidence Review: A virtual 2-day roundtable comprising 40 individuals convened on May 24 and May 26, 2022, and used a virtual Delphi method to arrive at expert group consensus. Participants responded to 6 rounds of virtual Delphi discussion via email that prioritized research topics and agreement on recommendations. The roundtable was composed of individuals with lived experience of mental health and/or substance misuse, peer support specialists, recovery coaches, parents and caregivers of people with SMI, researchers and clinician-scientists with and without lived experience, policy makers, and patient-led organizations. Twenty-two of 28 (78.6%) of the authors who provided data represented people with lived experiences. Roundtable members were selected by reviewing the peer-reviewed and gray literature on early mortality and SMI, direct email, and snowball sampling., Findings: The following recommendations are presented in order of priority as identified by the roundtable participants: (1) improve the empirical understanding of the direct and indirect social and biological contributions of trauma on morbidity and early mortality; (2) advance the role of family, extended families, and informal supporters; (3) recognize the importance of co-occurring disorders and early mortality; (4) redefine clinical education to reduce stigma and support clinicians through technological advancements to improve diagnostic accuracy; (5) examine outcomes meaningful to people with an SMI diagnosis, such as loneliness and sense of belonging, and stigma and their complex relationship with early mortality; (6) advance the science of pharmaceuticals, drug discovery, and choice in medication use; (7) use precision medicine to inform treatment; and (8) redefine the terms system literacy and health literacy., Conclusions and Relevance: The recommendations of this roundtable are a starting point for changing practice and highlighting lived experience-led research priorities as an option to move the field forward.

Although there is ample evidence that PTSD is effectively treated by first-line therapies such as Cognitive Processing Therapy (CPT), it is less clear to what degree these treatments improve quality of life (QOL), a common presenting concern of treatment-seeking individuals (Rosen et al., 2013). Only two studies, both conducted in military veteran samples, have examined the magnitude of PTSD symptom change needed in order to achieve corresponding changes in QOL during treatment. The current study aimed to replicate and extend these two previous studies by benchmarking multi-faceted QOL in a civilian sample of primarily female interpersonal violence survivors (N = 115) treated with CPT. We grouped participants into categories of increasingly greater PTSD symptom change: no response, response, loss of diagnosis, and remission. Outcomes were clinically meaningful change and good endpoint across five measures of QOL. Some QOL measures showed clinically meaningful change and/or good endpoint after a response to treatment or loss of diagnosis, but only remission from PTSD was associated with both clinically meaningful change and a good endpoint across all QOL indicators. These findings add to the emerging literature showing that treating PTSD to remission may maximize the likelihood of improvements in quality of life., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: Individuals with serious mental illness (SMI) experience a 10-25-year reduced life expectancy when compared to the general population that is due, in part, to poor health behaviors. Yet, in spite of the development of health promotion and self-management interventions designed for people with SMI to promote health behavior change, the mortality gap has increased, suggesting that relevant factors are not being addressed. The objective of the present study was to explore potential contributors to early mortality among individuals with SMI by drawing from the lived experience of certified peer support specialists and service users (SUs)., Method: Face-to-face semistructured interviews were conducted with a convenience sample of SU participants ( n = 17) and certified peer specialists ( n = 15). Qualitative data were analyzed using a grounded-theory approach., Results: We identified a final set of 27 codes relating to five overarching themes that relate to both risk factors and protective factors for early death: social connectedness (24.1% of coded items), treatment (21.3%), coping (21.3%), physical health and wellness (18.5%), and resilience and mental health (14.8%)., Conclusions and Implications for Practice: Findings add to the literature supporting the powerful role of social processes in shaping health in people with SMI beyond social determinants of health (SDOH; e.g., income, employment) and health behavior change. Interventions that reduce loneliness and isolation in combination with addressing more conventional SDOH may have the most potential to reduce early mortality in people with SMI. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The association between symptoms of posttraumatic stress disorder (PTSD) in adults and difficulties in intimate relationships is well documented. Growing literature suggests that interpersonally-oriented therapies, such as couple and family interventions, may lead to improvements in both PTSD symptoms and intimate relationship functioning. However, it is unknown how individual PTSD treatments compare to couple/family interventions in relational outcomes. The present study was a systematic review and meta-analysis of individual and couple/family treatments to examine changes in PTSD symptoms and intimate relationship functioning. Twelve couple treatment studies with 13 unique samples and 7 individual treatment studies with 9 unique samples met inclusion criteria. No family-based treatments were identified. Meta-analytic findings indicated moderate to large reductions in PTSD symptoms for both couple and individual studies. Small but significant improvements in intimate relationship functioning across individual and couple studies were observed. Moderation analysis suggested that across both individual and couple treatment formats, trauma-focused treatments had larger effects on PTSD symptoms. Trauma-focused treatments had larger effects on intimate relationship functioning for individual studies. Military status did not moderate outcomes. This study supports the utility of both individual and couple treatment formats for treating PTSD and provides preliminary support for these modalities for also enhancing intimate relationship functioning., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Posttraumatic stress disorder (PTSD) is a significant mental health issue among military service members and veterans. Although the U.S. Department of Veterans Affairs (VA) provides crucial resources for behavioral health care, many veterans seek mental health services through community clinics. Previous research illustrates that military and veteran patients benefit less from evidence-based treatments (EBTs) for PTSD than civilians. However, most PTSD treatment outcome research on military and veteran populations is conducted in VA or military settings. Little is known about outcomes among military-affiliated patients in community settings. The primary aim of this study was to directly compare civilian versus military-affiliated patient outcomes on PTSD and depression symptoms using the PTSD Checklist for DSM-5 (PCL-5) and the nine-item Patient Health Questionnaire (PHQ-9) in a community setting. Participants (N = 502) included military-affiliated (veteran, Guard/Reservist, active duty) and civilian patients who engaged in cognitive processing therapy (CPT) or prolonged exposure (PE) for PTSD in community clinics. Both groups demonstrated significant reductions on the PCL-5, military-affiliated: d = -0.91, civilian: d = -1.18; and PHQ-9, military-affiliated: d = -0.65, civilian: d = -0.88, following treatment. However, military-affiliated patients demonstrated smaller posttreatment reductions on the PCL-5, M diff = 5.75, p = .003, and PHQ-9, M diff = 1.71, p = .011, compared to civilians. Results demonstrate that military-affiliated patients benefit from EBTs for PTSD, albeit to a lesser degree than civilians, even in community settings. These findings also highlight the importance of future research on improving EBTs for military personnel with PTSD., (© 2022 International Society for Traumatic Stress Studies.)

Aggressive behavior is a major public health issue for which there are few efficacious treatments. Although much of information processing is automatic, there are few studies of early-stage decoding biases (e.g., attention bias to threat) and aggressive behavior, potentially resulting in missed opportunities for identifying targets of intervention. Previous studies are limited by indirect measures of attention bias and little consideration of proximal factors like state fear, which organizes perception and motivates defensive behaviors. We used laboratory methods (i.e., eye-tracking, idiographic mood induction, and the Point Subtraction Aggression Paradigm), to examine the association between attention bias to physical and negative evaluation threat and in vivo defensive responding (i.e., aggression and escape) and the potential moderating role of state fear among 74 undergraduate students. As predicted, attention bias to threat was positively associated with in vivo aggression. Fear did not potentiate aggression or modify the relationship between attentional bias to threat and aggression; however, in the fear condition, greater attentional bias to threat was associated with less escape behavior. Findings add to the sparse literature identifying early-stage decoding processes as possible risk factors of aggression and suggest a need for additional research on freeze behavior in response to threat and provocation., (Published by Elsevier Ltd.)

Purpose: Healthcare workers are at increased risk for mental health problems during disasters such as the COVID-19 pandemic. Identifying resilience mechanisms can inform development of interventions for this population. The current study examined pathways that may support healthcare worker resilience, specifically testing enabling (social support enabled self-efficacy) and cultivation (self-efficacy cultivating support) models., Methods: Healthcare workers (N = 828) in the Rocky Mountain West completed self-report measures at four time points (once per month from April to July of 2020). We estimated structural equation models to explore the potential mediating effects that received social support and coping self-efficacy had (at time 2 and time 3) between traumatic stress symptom severity (at time 1 and time 4). Models included covariates gender, age, minority status, and time lagged co-variations between the proposed mediators (social support and coping self-efficacy)., Results: The full model fit the data well, CFI = .993, SRMR = .027, RMSEA = .036 [90% CIs (0.013, 0.057)]. Tests of sequential mediation supported enabling model dynamics. Specifically, the effects of time 1 traumatic stress severity were mediated through received social support at time 2 and time 3 coping self-efficacy, in sequential order to reduce time 4 traumatic stress severity., Conclusions: Findings show the importance of received social support and coping self-efficacy in mitigating psychopathology risk. Interventions can support mental health by focusing on social resource engagement that facilitates coping empowerment, which may decrease risk for mental health job-related problems among frontline healthcare workers exposed to highly stressful events., (© 2022. The Author(s).)

Posttraumatic stress disorder (PTSD) is a well-established risk factor for suicidal thoughts and behaviors. Historically, guidelines for treating PTSD have recommended against the use of trauma-focused therapies for patients who are at high risk for suicide, likely due to concerns about potential suicide-related iatrogenesis, specifically the "triggering" of suicidal behaviors. This systematic review examined evidence of the impact of treatments specifically designed to treat PTSD or suicide on both PTSD- and suicide-related outcomes. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and a total of 33 articles met the full inclusion criteria: 23 examining PTSD treatments, four examining suicide-focused treatments, and six examining combined treatments. PTSD and combined treatments reduced both PTSD- and suicide-related outcomes, with most studies focusing on cognitive processing therapy or prolonged exposure. Suicide-focused treatments (e.g., cognitive therapies for suicide prevention) also reduced suicide-related outcomes, but the findings were mixed for their impact on PTSD-related outcomes. Overall, PTSD treatments had the most support, primarily due to a larger number of studies examining their outcomes. This supports current clinical guidelines, which suggest utilizing PTSD treatments for individuals who have PTSD and are at risk for suicide. Suicide-focused and combined treatments also appeared to be promising formats, although additional research is needed. Future research should seek to compare the effectiveness of the approaches to the treatment of PTSD and suicidal thoughts and behaviors concurrently as well as to inform guidelines aimed at supporting decisions about the selection of an appropriate treatment approach., (© 2021 International Society for Traumatic Stress Studies.)

Background: Posttraumatic stress disorder (PTSD) develops consequent to complex gene-by-environment interactions beyond the precipitating trauma. To date, however, no known study has used a prospective design to examine how polygenic risk scores (PRSs) interact with social-environmental factors such as attachment style to predict PTSD development., Methods: PRSs were derived from a genome-wide association study of PTSD symptoms (N = 186,689; Million Veteran Program cohort). We evaluated combined effects of PRS and attachment style in predicting incident PTSD in a 7-year, nationally representative cohort of trauma-exposed, European-American U.S. military veterans without PTSD (N = 1083). We also conducted multivariate gene-by-environment interaction and drug repositioning analyses to identify loci that interact with multiple environmental factors and potential pharmacotherapies that may be repurposed for this disorder., Results: Veterans with higher PTSD PRS were more likely to have an incident-positive screen for PTSD over 7 years. A gene-by-environment interaction was also observed, such that higher PRS only predicted incident PTSD in veterans with an insecure attachment style and not those with a secure attachment style. At an individual locus level, the strongest gene-by-environment interaction was observed for the rs4702 variant of the FURIN gene with cumulative lifetime trauma burden. Drug repositioning revealed that genes implicated in PRS are perturbated by the drug doxylamine., Conclusions: Attachment style moderates polygenic risk for the development of PTSD in European-American veterans. These findings may inform PTSD prevention and treatment for veterans with high polygenic risk for PTSD and suggest a potential pharmacotherapeutic target for risk genes moderated by social-environmental factors., (Copyright © 2021 Society of Biological Psychiatry. All rights reserved.)

Objective: This study aimed to characterize the current prevalence of loneliness, and the relation between loneliness severity and mental and physical health conditions, suicidality, and functional measures in a predominantly older sample of U.S. military veterans., Methods: This cross-sectional study used data from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of U.S. veterans (N = 4,069; mean age = 62) from November 2019 through March 2020. Veterans were classified into one of 3 groups based on their current level of loneliness (hardly ever, sometimes, often) on an adapted version of the Revised UCLA Loneliness Scale. A comprehensive range of mental and physical health, and functioning variables were assessed using valid and reliable self-report assessments., Results: A total of 56.9% of veterans endorsed feeling lonely sometimes (37.2%) or often (19.7%). Loneliness severity was independently associated with a range of mental health (odds ratios [ORs] = 1.21-33.30), physical health (ORs = 1.21-6.80), and functional difficulties (d's = 0.09-0.59). Relative to hardly ever feeling lonely, feeling lonely often or sometimes was associated with a more than 12- and three-fold greater likelihood of current suicidal ideation (29.0% versus 7.3% versus 1.5%), even after adjustment for sociodemographic, military, and psychiatric risk factors., Conclusions: Loneliness is highly prevalent in U.S. military veterans, with more than half endorsing feeling lonely sometimes or often, and 1-of-5 reporting feeling lonely often. Loneliness severity was independently associated with a broad range of mental and physical health and functional measures, ias well as suicidal ideation. Results underscore the importance of loneliness as a transdiagnostic prevention and intervention target in the U.S. veteran population., (Copyright © 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Novel treatments that target neurobiological alterations associated with childhood trauma, particularly among those with posttraumatic stress disorder (PTSD), could mitigate negative outcomes for these at-risk individuals. PTSD is characterized by abnormalities within the brain's salience network and reward circuitry, which are modulated by intranasal oxytocin. Using a double-blind, randomized, placebo-controlled crossover design, we tested whether intranasal oxytocin (24 international units) influenced functional coupling of the amygdala with the anterior insula (AI), dorsal anterior cingulate cortex, and nucleus accumbens in response to implicitly presented fearful, angry, and happy faces among childhood trauma-exposed individuals with (n = 16, 9 women) and without PTSD (n = 18, 12 women). Psychophysiological interaction analyses revealed that oxytocin effects were limited to amygdala-AI connectivity in the fear condition, distinct for men and women, and not impacted by PTSD diagnosis. In response to fear faces, oxytocin reduced left amygdala-left AI connectivity for women but not men; reduced left amygdala-right AI connectivity among women, but increased this connectivity in men; and reduced right amygdala-right anterior insula connectivity for men, but increased it for women. Results suggest that intranasal oxytocin modulates threat salience among childhood trauma-exposed individuals and that these effects vary as a function of gender and hemisphere., (Published by Elsevier B.V.)

Background: Poor social connection is a central feature of posttraumatic stress disorder (PTSD), but little is known about the neurocognitive processes associated with social difficulties in this population. We examined recruitment of the default network and behavioral responses during social working memory (SWM; i.e., maintaining and manipulating social information on a moment-to-moment basis) in relation to PTSD and social connection., Methods: Participants with PTSD (n = 31) and a trauma-exposed control group (n = 21) underwent functional magnetic resonance imaging while completing a task in which they reasoned about two or four people's relationships in working memory (social condition) and alphabetized two or four people's names in working memory (nonsocial condition). Participants also completed measures of social connection (e.g., loneliness, social network size)., Results: Compared to trauma-exposed controls, individuals with PTSD reported smaller social networks (p = .032) and greater loneliness (p = .038). Individuals with PTSD showed a selective deficit in SWM accuracy (p = .029) and hyperactivation in the default network, particularly in the dorsomedial subsystem, on trials with four relationships to consider. Moreover, default network hyperactivation in the PTSD group (vs. trauma-exposed group) differentially related to social network size and loneliness (p's < .05). Participants with PTSD also showed less resting state functional connectivity within the dorsomedial subsystem than controls (p = .002), suggesting differences in the functional integrity of a subsystem key to SWM., Conclusions: SWM abnormalities in the default network may be a basic mechanism underlying poorer social connection in PTSD., (© 2021 Wiley Periodicals LLC.)

Background: A polygenic risk score (PRS) derived from genome-wide association studies of posttraumatic stress disorder (PTSD) may inform risk for this disorder. To date, however, no known study has examined whether social environmental factors such as attachment style may moderate the relation between PRS and PTSD., Methods: We evaluated main and interactive effects of PRS and attachment style on PTSD symptoms in a nationally representative sample of trauma-exposed European-American U.S. military veterans (N = 2030). PRS was derived from a genome-wide association study of PTSD re-experiencing symptoms (N = 146,660) in the Million Veteran Program cohort. Using one-sample Mendelian randomization with data from the UK Biobank (N = 115,099), we evaluated the effects of re-experiencing PRS and attachment style on PTSD symptoms., Results: Higher re-experiencing PRS and secure attachment style were independently associated with PTSD symptoms. A significant PRS-by-attachment style interaction was also observed (β = -.11, p = .006), with a positive association between re-experiencing PRS and PTSD symptoms observed only among veterans with an insecure attachment style. One-sample Mendelian randomization analyses suggested that the association between PTSD symptoms and attachment style is bidirectional. PRS enrichment analyses revealed a significant interaction between attachment style and a variant mapping to the IGSF11 gene (rs151177743, p = 2.1 × 10 -7 ), which is implicated in regulating excitatory synaptic transmission and plasticity., Conclusions: Attachment style may moderate polygenic risk for PTSD symptoms, and a novel locus implicated in synaptic transmission and plasticity may serve as a possible biological mediator of this association. These findings may help inform interpersonally oriented treatments for PTSD for individuals with high polygenic risk for this disorder., (Copyright © 2020 Society of Biological Psychiatry. All rights reserved.)

Introduction: Focal brain stimulation has potential as a treatment for posttraumatic stress disorder (PTSD). In this review, we aim to inform selection of focal brain stimulation targets for treating PTSD by examining studies of the functional neuroanatomy of PTSD and treatment response. We first briefly review data on brain stimulation interventions for PTSD. Although published data suggest good efficacy overall, the neurobiological rationale for each stimulation target is not always clear., Methods: Therefore, we assess pre- and post-treatment (predominantly psychotherapy) functional neuroimaging studies in PTSD to determine which brain changes seem critical to treatment response. Results of these studies are presented within a previously proposed functional neural systems model of PTSD., Results: While not completely consistent, research suggests that downregulating the fear learning and threat and salience detection circuits (i.e., amygdala, dorsal anterior cingulate cortex and insula) and upregulating the emotion regulation and executive function and contextual processing circuits (i.e., prefrontal cortical regions and hippocampus) may mediate PTSD treatment response., Conclusion: This literature review provides some justification for current focal brain stimulation targets. However, the examination of treatment effects on neural networks is limited, and studies that include the stimulation targets are lacking. Further, additional targets, such as the cingulate, medial prefrontal cortex, and inferior parietal lobe, may also be worth investigation, especially when considering how to achieve network level changes. Additional research combining PTSD treatment with functional neuroimaging will help move the field forward by identifying and validating novel targets, providing better rationale for specific treatment parameters and personalizing treatment for PTSD., (© 2021 Wiley Periodicals LLC.)

Background: Preclinical and clinical research suggests that the oxytocin system is implicated in the development and maintenance of stress and anxiety-related psychiatric conditions, such as posttraumatic stress disorder (PTSD). Recent research also suggests that intranasal oxytocin holds promise as a treatment for PTSD. However, little is known about the relationship between levels of peripheral oxytocin and PTSD symptom severity, PTSD treatment response, and repeated intranasal oxytocin administration., Methods: In the current study, we examined associations between PTSD symptom severity and peripheral oxytocin levels measured in plasma before and after a course of prolonged exposure (PE) for PTSD (n = 13); participants were randomized to adjunctive intranasal oxytocin (n = 6) or placebo (n = 7)., Results: Baseline peripheral oxytocin levels were not associated with baseline PTSD symptom severity. Change in peripheral oxytocin levels did not differ by treatment condition and did not correspond to change in PTSD symptoms., Conclusions: This proof-of-concept study illustrates the acceptability and feasibility of measuring peripheral oxytocin among individuals engaged in psychotherapy for PTSD and informs the utilization of these procedures in future adequately powered studies.

Background: Suicidal thoughts are common among veterans with posttraumatic stress disorder (PTSD). The aim of this study was to examine the prevalence and correlates of four courses of suicidal (SI) among veterans receiving residential PTSD treatment., Methods: A total of 1,807 veterans receiving residential PTSD treatment at Department of Veterans Affairs medical facilities who completed self-report measures at admission and discharge were included., Results: The prevalence of SI courses were No SI (33.6%), Remitted SI (23.0%), SI onset (6.0%), and Chronic SI (37.4%). There were group differences between the four SI courses in PTSD symptoms at baseline, magnitude of PTSD symptom change during treatment, race/ethnicity and baseline depression, substance use, physical functioning, and pain. Chronic SI was associated with highest baseline PTSD, depression, substance use, pain and worse physical functioning. Remitted SI course was associated with greatest pre-posttreatment PTSD improvement, followed by No SI, Chronic SI, and SI Onset. Multinomial logistic regressions revealed that PTSD symptom improvement and baseline PTSD symptoms most consistently related to symptomatic SI courses compared to less symptomatic or No SI courses. Receipt of trauma-focused psychotherapy (none, some, or adequate) and length of stay were not related to SI courses and did not differ between groups., Conclusions: Findings indicate that treating PTSD symptoms could be impactful for reducing suicidal thoughts. Although many veterans had remitted or reduced severity of SI at discharge, a significant proportion of veterans reported SI at discharge (43.4%), potentially highlighting the need for suicide specific treatment interventions within the context of PTSD treatment., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Veterans are at high risk for suicide; emotion dysregulation may confer additional risk. Dialectical behaviour therapy (DBT) is a well-supported intervention for suicide attempt reduction in individuals with emotion dysregulation, but is complex and multi-component. The skills group component of DBT (DBT-SG) has been associated with reduced suicidal ideation and emotion dysregulation. DBT-SG for Veterans at risk for suicide has not been studied., Aims: This study sought to evaluate the feasibility and acceptability of DBT-SG in Veterans and to gather preliminary evidence for its efficacy in reducing suicidal ideation and emotion dysregulation and increasing coping skills., Method: Veterans with suicidal ideation and emotion dysregulation (N = 17) enrolled in an uncontrolled pilot study of a 26-week DBT-SG as an adjunct to mental health care-as-usual., Results: Veterans attended an average 66% of DBT-SG sessions. Both Veterans and their primary mental health providers believed DBT-SG promoted Veterans' use of coping skills to reduce suicide risk, and they were satisfied with the treatment. Paired sample t-tests comparing baseline scores with later scores indicated suicidal ideation and emotion dysregulation decreased at post-treatment (d = 1.88, 2.75, respectively) and stayed reduced at 3-month follow-up (d = 2.08, 2.59, respectively). Likewise, skillful coping increased at post-treatment (d = 0.85) and was maintained at follow-up (d = 0.91)., Conclusions: An uncontrolled pilot study indicated DBT-SG was feasible, acceptable, and demonstrated potential efficacy in reducing suicidal ideation and emotion dysregulation among Veterans. A randomized controlled study of DBT-SG with Veterans at risk for suicide is warranted.

Elucidating whether PTSD symptoms predict poorer social connectedness over time (i.e. social erosion) and/or that poor social connectedness contributes to maintenance of PTSD (i.e. social causation) has implications for PTSD treatment and relapse prevention. Most extant research has been cross-sectional and examined overall PTSD symptoms. Evidence of longitudinal associations among heterogeneous PTSD symptom clusters and social connectedness could provide insight into more nuanced targets for intervention. Using data from 1,491 U.S. military veterans in residential treatment for PTSD at 35 Department of Veterans Affairs facilities, we evaluated a two-wave cross-lagged panel model including a five-factor model of PTSD and two aspects of social connectedness. PTSD, quality of connectedness (i.e. degree of distress related to interpersonal conflict), and structural social support (i.e. number of days of contact with supportive loved ones) in the past 30 days were assessed at baseline and 4 months after discharge. The largest effect was greater severity of PTSD dysphoric arousal symptoms (i.e. irritability/anger, poor concentration, and sleep problems) at baseline predicting more conflict-related distress at follow-up (β = 0.43). Post-hoc symptom-level analyses indicated that irritability/anger drove this association. In addition, conflict-related distress predicted greater PTSD symptom severity across all five clusters (β's = 0.10 to 0.14, p 's < 0.01). More days of contact predicted lower severity of avoidance and numbing symptoms (β's = -.05 and -.07, p 's < 0.01), along with individual symptoms within these clusters, plus flashbacks. Results support both social erosion and social causation models. Engaging loved ones in veterans' treatment and targeting dysphoric arousal symptoms, particularly anger and irritability, may improve long-term PTSD and relationship outcomes, respectively.

Aim: This study examined the short-term effects of a brief crisis intervention on optimism of acutely suicidal soldiers., Methods: U.S. Soldiers (N = 97) presenting for an emergency mental health appointment in a military emergency department or behavioural health clinic were randomly assigned to treatment as usual standard crisis response plan, or enhanced crisis response plan (E-CRP). This study is used a subsample of the original clinical trial (n = 64) for those who completed self-report measures of optimism (Life Orientation Test-Revised) prior to receiving any intervention and a secondary self-report assessment one-month following the intervention., Results: Results indicate that individuals with low baseline optimism who received the E-CRP had significant increases in optimism 1 month post-intervention., Conclusion: This provides evidence that discussing a patient's reasons for living during a CRP increases optimism in those high-risk patients with the lowest baseline optimism., (© 2018 John Wiley & Sons Australia, Ltd.)

Background : Posttraumatic stress disorder (PTSD) related to exposure to abuse and neglect during childhood is associated with particularly severe and persistent deleterious outcomes. Amygdala hyperreactivity has been observed in childhood trauma survivors and implicated in symptoms of PTSD. Objective : The neuropeptide oxytocin holds promise as a potential treatment for PTSD due to its ability to attenuate amygdala response to threat cues. However, the effect of oxytocin on amygdala reactivity in individuals with childhood trauma-related PTSD has not been investigated. Method : We employed a double-blind, randomized, placebo-controlled crossover design to examine the effects of intranasal oxytocin (24 IU) versus placebo on amygdala reactivity to fearful faces among childhood-trauma exposed individuals with PTSD ( n = 17) and without PTSD (control group; n = 16). Results : Region-of-interest based amygdala fMRI signal magnitude did not differ by group, drug, or group x drug interaction. Self-report of childhood trauma exposure severity was negatively associated with the oxytocin-related change in left amygdala response in the PTSD group, but not in the control group. Supplementary and exploratory whole-brain analyses conducted separately in each group revealed that left amygdala reactivity to fearful faces was absent on placebo but increased on oxytocin in the control group. The PTSD group showed right amygdala activation to fearful faces in both the oxytocin and placebo conditions, but the left amygdala response observed in the placebo condition was diminished on oxytocin. Conclusions : Findings extend the literature pertaining to the potential for oxytocin to attenuate neural correlates of PTSD to a childhood trauma-related PTSD sample.

Objectives: To determine the main and interactive effects of four FKBP5 polymorphisms (rs9296158, rs3800373, rs1360780 and rs9470080), childhood abuse and attachment style in predicting severity of PTSD symptoms in two independent, nationally representative samples of US military veterans. Methods: Data were analysed from two independent samples of European-American US military veterans who participated in the National Health and Resilience in Veterans Study ( N  = 1,585 and 577 respectively). Results: Results revealed that carriage of two FKBP5 minor alleles, childhood abuse and insecure attachment style were associated with greater severity of PTSD symptoms. Gene × environment interactions were also observed, with the interaction of FKBP5 homozygous minor allele carriage and history of childhood abuse associated with greater severity of PTSD symptoms; however, these effects were fully counteracted by secure attachment style. Conclusions: Results of this study build on prior work demonstrating a gene × environment interaction between FKBP5 polymorphisms and childhood abuse in predicting risk for PTSD by suggesting that attachment style may moderate this effect. This study has implications for prevention and treatment efforts designed to promote a secure attachment style in veterans with high-risk FKBP5 genotypes and childhood abuse histories.

Background: Successful psychotherapy for posttraumatic stress disorder (PTSD) necessitates initial and sustained engagement. However, treatment dropout is common, with rates of 50-70% depending on the setting, type of treatment and how dropout is calculated. Dropout from residential treatment is less understood and could be impacted by participation of more symptomatic patient populations and reduced day-to-day barriers to engagement. Gaining insight into predictors of treatment dropout is critical given that individuals with greater symptoms are the most in need of successful treatments but also at higher risk of unsuccessful psychotherapy episodes. Aim: The aim of the current study was to examine predictors of treatment dropout among veterans receiving residential treatment for PTSD. Methods: The study included 3,965 veterans who initiated residential PTSD treatment within a Department of Veterans Affairs program during Fiscal Year 2015 and completed self-report measures of demographics and psychiatric symptoms at admission. Results: In our sample ( N = 3,965, 86.5% male, mean age = 45.5), 27.5% did not complete the residential program ( n = 1,091). Controlling for age, marital status, combat/non-combat trauma, and facility, generalized estimating equation modeling analysis indicated greater PTSD symptoms and physical functioning at admission were associated with reduced likelihood of completing the residential program. There were significant differences in trauma-focused psychotherapy received by individuals who dropped out of residential treatment and those who did not. Among veterans who dropped out, 43.6% did not get any trauma-focused psychotherapy; 22.3% got some, but less than 8 sessions; and 34.1% got at least 8 sessions; compared to 37.3%, 4.8%, and 57.9%, respectively, among program completers. Conclusion: Dropout rates from residential PTSD programs indicate that at least one in four veterans do not complete residential treatment, with more symptomatic individuals and those who do not receive trauma-focused therapy being less likely to complete.

Given elevated rates of posttraumatic stress disorder (PTSD) among US military veterans, identifying correlates of PTSD and specific PTSD symptom clusters that best represent PTSD in veterans (i.e., the five-factor Dysphoric Arousal model) is critical to prevention and intervention efforts. One potential correlate is locus of control (i.e., the extent to which individuals believe they have control over events in their lives). The aim of this study was to examine the relations between locus of control and five-factor model PTSD symptom clusters (i.e., re-experiencing, avoidance, numbing, dysphoric arousal, anxious arousal) among combat veterans. Eighty-nine combat exposed veterans completed self-report measures of demographics, locus of control, PTSD symptoms, and combat exposure. Bivariate correlations indicated relations between locus of control and overall PTSD symptoms, avoidance symptoms, and numbing symptoms. When controlling for sex and combat exposure in regression analyses, only avoidance remained a significant correlate of locus of control. Among veterans with the most extreme scores (n = 26), external locus of control predicted overall PTSD symptoms and avoidance symptoms. External locus of control is uniquely associated with avoidance symptoms, and represents a potentially modifiable factor to address in trauma-focused treatments., (Published by Elsevier B.V.)

Objective: While poor social connectedness is often a consequence of living with posttraumatic stress disorder (PTSD) symptoms, little is known about whether PTSD symptom clusters may be uniquely related to different aspects of social connectedness. This information can inform case conceptualization and treatment planning to potentially facilitate sustained recovery for individuals with PTSD., Method: We examined associations among a five-factor model of PTSD and two aspects of social connectedness-distress related to problems getting along with others and days of contact with supportive loved ones in the past 30 days-in a sample of 2,600 U.S. military veterans seeking residential treatment for PTSD., Results: A large proportion of veterans reported experiencing distress related to problems getting along with others (66.2%) and few days of contact with supportive people (43.5%). Ordinal regression models controlling for intercorrelations among PTSD symptom clusters revealed that emotional numbing symptoms were independently associated with greater distress (β = 0.130, p < 0.001) and fewer days of contact (β = -0.159, p < 0.001); dysphoric arousal symptoms were associated with more distress (β = 0.236, p < 0.001), while anxious arousal was associated with more days of contact (β = 0.058, p < 0.05)., Conclusions: Findings reveal high rates of difficulties in social connectedness and distinct associations among these difficulties with emotional numbing, dysphoric arousal, and anxious arousal symptoms in veterans receiving residential treatment for PTSD. Future studies should examine whether targeting poor social connectedness during treatment improves interpersonal functioning and supports sustained trauma recovery, which may be particularly beneficial to veterans with more severe emotional numbing and dysphoric arousal symptoms.

Objective: Resilience has been associated with less severe psychiatric symptomatology and better treatment outcomes among individuals with posttraumatic stress disorder (PTSD) and substance use disorders. However, it remains unknown whether resilience increases during psychotherapy within the comorbid PTSD and substance use disorder population with unique features of dual diagnosis, including trauma cue-related cravings. We tested whether veterans seeking psychotherapy for comorbid PTSD and substance use disorder reported increased resilience from pre- to posttreatment. We also tested whether increased resilience was associated with greater decreases in posttreatment PTSD and substance use disorder symptoms., Methods: Participants were 29 male veterans (M age = 49.07 years, SD = 11.24 years) receiving six-week residential day treatment including cognitive processing therapy for PTSD and cognitive behavioral therapy for substance use disorder. Resilience, PTSD symptoms, and trauma cue-related cravings were assessed at pre- and posttreatment., Results: Veterans reported a large, significant increase in resilience posttreatment (M diff = 14.24, t = -4.22, p < .001, d = 0.74). Greater increases in resilience were significantly associated with fewer PTSD symptoms (β = -0.37, p = .049, sr = -.36) and trauma-cued cravings (β = -0.39, p = .006, sr = -.38) posttreatment when controlling for pretreatment scores and baseline depressive symptoms., Conclusions: Results suggest that evidence-based psychotherapy for comorbid PTSD and substance use disorder may facilitate strength-based psychological growth, which may further promote sustained recovery.

Although the link between posttraumatic stress disorder (PTSD) and aggression has been repeatedly demonstrated, to our knowledge no research has examined whether PTSD symptom reductions are linked to less aggression after treatment. The current study aimed to address this gap in the literature by examining the association between reductions in PTSD symptoms and posttreatment aggression among 2,275 veterans in residential treatment for PTSD across 35 Veterans Health Administration sites. We estimated a multilevel model that examined the effect of clinically significant PTSD symptom change on aggression at 4-month posttreatment follow-up, and found significant within-site and between-site contextual effects of clinically significant changes in PTSD symptoms on follow-up aggression. Findings revealed that veterans who reported clinically significant changes in their PTSD symptoms had lower levels of aggression at follow-up than veterans at the same treatment site who did not report clinically significant PTSD change. After we controlled for individual clinically significant PTSD change, participants in treatment sites where the rates of clinically significant PTSD change were higher overall had lower levels of aggression at follow-up. The model explained over one-fourth of the variability in aggression, R 2 = .26. Findings from the current study extend previous research that has shown associations between PTSD and aggression, by revealing that clinically significant change in PTSD during residential treatment is associated with less aggression at follow-up. These findings suggest that interventions that effectively reduce PTSD symptoms may also help reduce risk for aggression., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition for which Prolonged Exposure (PE) therapy is highly efficacious. However, for some individuals, premature dropout and residual PTSD symptoms remain obstacles. The neuropeptide oxytocin is a promising candidate to enhance PE due to its ability to enhance 1) prosocial cognition and behavior, which are theorized to promote positive working alliance, and 2) extinction learning, which is the central mechanism of action underlying successful PE treatment. Despite a robust theoretical rationale, no studies to date have combined evidence-based psychotherapy for PTSD with oxytocin. This randomized, placebo-controlled, double-blind pilot trial examined the feasibility, safety, and preliminary efficacy of augmenting PE with oxytocin. Participants were 17 individuals with diverse index traumas. Participants self-administered intranasal oxytocin (40 IU) or matching placebo 45 min prior to each weekly PE therapy session. One adverse event occurred in the placebo group and three individuals dropped out (17.6%; 2 oxytocin group and 1 placebo group). The oxytocin group demonstrated lower PTSD and depression symptoms during PE, and had higher working alliance scores, although these differences did not reach statistical significance. Although preliminary, the findings support the feasibility of oxytocin combined with PE. Adequately powered studies are necessary to determine whether oxytocin enhances PE treatment outcomes and to examine potential mechanisms, such as accelerating extinction learning, enhancing early response, and preventing premature dropout. NCT03238924., (Copyright © 2017. Published by Elsevier Ltd.)

The human oxytocin system is implicated in social behavior and stress recovery. Polymorphisms in the oxytocin receptor gene (OXTR) may interact with attachment style to predict stress-related psychopathology like posttraumatic stress disorder (PTSD). The objective of this study was to examine independent and interactive effects of the OXTR single nucleotide polymorphism (SNP) rs53576, which has been associated with stress reactivity, support-seeking, and PTSD in prior studies, and attachment style on risk for PTSD in a nationally representative sample of 2163 European-American (EA) U.S. military veterans who participated in two independent waves of the National Health and Resilience in Veterans Study (NHRVS). Results revealed that insecure attachment style [adjusted odds ratio (OR) = 4.29; p < 0.001] and the interaction of rs53576 and attachment style (OR = 2.58, p = 0.02) were associated with probable lifetime PTSD. Among individuals with the minor A allele, the prevalence of probable PTSD was significantly higher among those with an insecure attachment style (23.9%) than those with a secure attachment style (2.0%), equivalent to an adjusted OR of 10.7. We attempted to replicate these findings by utilizing dense marker data from a genome-wide association study of 2215 high-risk civilians; one OXTR variant, though not rs53576, was associated with PTSD. Exploratory analyses in the veteran sample revealed that the interaction between this variant and attachment style predicting probable PTSD approached statistical significance. Results indicate that polymorphisms in the OXTR gene and attachment style may contribute to vulnerability to PTSD in U.S. military veterans., (Published by Elsevier Ltd.)

Posttraumatic stress disorder (PTSD) is associated with alterations in critical brain regions such as the amygdala, hippocampus, and prefrontal cortex. This brief review has two objectives: (1) to discuss research examining extinction and reconsolidation processes as mechanisms in PTSD psychotherapy, and (2) present possibilities for augmenting extinction and reconsolidation within treatment through alterations to therapeutic interventions and novel approaches. A key component of many effective PTSD therapies is exposure, which involves intentional confrontation and processing of the traumatic memory. Our review suggests that extinction and reconsolidation processes underlie effective exposure-based treatment, but the neurobiological mechanisms of these processes in behavioral treatments for PTSD remains unclear. We argue that enhancing extinction and/or disrupting reconsolidation of a feared memory may improve the efficacy of existing treatments (e.g., increased change for limited/non-responders, faster/greater changes for responders), which can be done through multiple channels. Potential avenues for augmentation of the processes of extinction and reconsolidation in PTSD psychotherapies are reviewed, including behavioral modifications, pharmacotherapy agents, and the use of devices during therapy. We further suggest that investigations towards understanding the extent to which extinction and reconsolidation processes are necessary in effective PTSD psychotherapy is an important future direction for enhancing clinical care among PTSD populations., (Published by Elsevier B.V.)

Aggression and suicidality are two serious public health concerns among U.S. veterans that can co-occur and share many overlapping risk factors. The current study aims to elucidate the contribution of posttraumatic stress disorder (PTSD) symptom clusters defined by a five-factor model and alcohol misuse in predicting aggression and suicide attempts among veterans entering residential treatment for PTSD. Participants were 2570 U.S. veterans across 35 Veterans Health Administration sites. Multinomial logistic regression models were used to identify correlates of aggression only (n = 1471; 57.2%), suicide attempts only (n = 41; 1.6%), co-occurring aggression and suicide attempts (n = 202; 7.9%), and neither behavior (n = 856; 33.3%) over the past four months. When compared to veterans endorsing neither behavior, greater PTSD re-experiencing symptoms were related to suicide attempts (odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.09-2.30), aggression (OR = 1.13, 95% CI = 1.02-1.26), and co-occurring aggression and suicide (OR = 1.38, 95% CI = 1.13-1.68), and higher PTSD dysphoric arousal symptoms and alcohol misuse symptoms were related to aggression (OR = 1.54, 95% CI = 1.38-1.71; OR = 1.30, 95% CI = 1.18-1.44, respectively) and co-occurring aggression and suicide (OR = 1.66, 95% CI = 1.35-2.04; OR = 1.50, 95% CI = 1.28-1.75, respectively). Our findings suggest that assessment of PTSD symptom clusters and alcohol misuse can potentially help to identify veterans who endorse suicide attempts, aggression, or both concurrently. These results have important implications for risk assessment and treatment planning with U.S. veterans seeking care for PTSD., (Published by Elsevier Ltd.)

Novel pharmacotherapies that improve outcomes for individuals with stress-related psychiatric disorders are needed. The neurohormone oxytocin (OT) is a promising candidate given its influence on the social-emotional brain. In this review, we present an overview of evidence supporting OT's utility for treating major depressive disorder and posttraumatic stress disorder. We first discuss endogenous OT, which research suggests is not yet a reliable biomarker of stress-related disorders. Second, we review effects of intranasal (IN) OT on processes relevant to stress-related disorders in healthy populations (anhedonia, reward processing, psychosocial stress reactivity, fear/anxiety, and social behavior) and their neurobiological mechanisms (e.g., the salience network and hypothalamic-pituitary-adrenal axis). Third, we present the sparse but promising findings from clinical populations, followed by discussion of critical moderating variables to consider in the service of maximizing the therapeutic potential of OT (e.g., patient sex and child maltreatment). We also identify heterogeneous findings and limitations of existing research, including reliance on single-dose studies in psychiatrically healthy samples and unanswered questions regarding the effectiveness of IN drug delivery and dosing schedules. Well-controlled multidose studies including women and measures of potentially moderating variables are sorely needed and would inform our understanding of the utility of OT for preventing and treating stress-related psychiatric disorders., Competing Interests: Declaration of Conflicting Interests The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Pietrzak has received travel funds from Johnson & Johnson for work that is unrelated to this project.

Chronic disorders of aging are critical concerns for the U.S. veteran population, which is, on average, two decades older than the non-veteran population. Characterization of risk factors that may accelerate biological aging is important in identifying targets for prevention and intervention. In the current study, we analyzed data from a contemporary, and nationally representative sample of U.S. veterans to evaluate the relationship between a broad range of sociodemographic, military, and clinical variables, and peripheral telomere length, which is an indicator of biological age and linked to risk for aging-related disorders and mortality. Data from 468U.S. military veterans who participated in the National Health and Resilience in Veterans Study were analyzed. Telomere length was assessed from cells isolated from saliva using quantitative polymerase chain reaction methods. A multivariable binary logistic regression analysis was conducted to evaluate the relations between hostility and telomere length, while controlling for sociodemographic, military, and clinical variables. Greater scores on a measure of hostility were independently associated with telomere shortening, even after adjustment for a broad range of other variables (odds ratio [OR]=1.58, 95% confidence interval [CI]=1.15-2.18). Secondary analyses revealed that this association was driven by difficulties controlling anger (OR=1.72, 95%CI=1.14-2.61), which reflect the external manifestation of hostility, rather than aggressive urges or impulses. Hostility, particularly difficulties controlling anger, is associated with peripheral telomere shortening in U.S. military veterans. Prevention and treatment efforts designed to reduce hostility may help mitigate risk for accelerated cellular aging in this growing segment of the U.S., (Published by Elsevier Ltd.)

Hostility is associated with substantial mental and physical health consequences. Population-based data regarding the nature and longitudinal course of hostility in U. S. veterans are scarce. We analyzed data from 2157 U. S. veterans who participated in the National Health and Resilience in Veterans Study, a nationally representative, prospective cohort study of U. S. veterans. We identified the prevalence of longitudinal courses of hostility (chronic, increasing, decreasing, or no hostility). We then evaluated relationships between sociodemographic, risk, and protective correlates measured at baseline and longitudinal courses of two aspects of hostility-aggressive urges and difficulties controlling anger. The majority of veterans (61.2%) reported experiencing difficulties controlling anger and a sizable minority of veterans (23.9%) reported experiencing aggressive urges over a two-year period. Protective psychosocial characteristics (e.g., optimism) and aspects of social connectedness (e.g., secure attachment style) were negatively associated with hostility. Psychological distress predicted all symptomatic hostility courses, while alcohol misuse predicted chronic aggressive urges and all symptomatic courses of difficulties controlling anger. These findings provide the first known population-based evaluation of the prevalence, course, and risk and protective correlates of hostility in U. S. veterans, and suggest targets for prevention and treatment efforts that can help mitigate risk for hostility in this population., (Published by Elsevier Ireland Ltd.)

Theories of posttraumatic stress disorder (PTSD) implicate emotional processes, including difficulties utilizing adaptive emotion regulation strategies, as critical to the etiology and maintenance of PTSD. Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn (OIF/OEF/OND) veterans report high levels of combat exposure and PTSD. We aimed to extend findings suggesting that emotion regulation difficulties are a function of PTSD, rather than combat trauma exposure or common comorbidities, to OIF/OEF/OND veterans, in order to inform models of PTSD risk and recovery that can be applied to returning veterans. We tested differences in emotion regulation, measured with the Difficulties in Emotion Regulation Scale and Emotion Regulation Questionnaire, among trauma-exposed veterans with (n = 24) or without PTSD (n = 22) and healthy civilian comparison participants (n = 27) using multivariate analyses of covariance, adjusting for major depressive disorder, anxiety disorders, and demographic variables (age, sex, and ethnicity). Veterans with PTSD reported more use of expressive suppression and more difficulties with emotion regulation than veterans without PTSD and healthy comparison participants. Groups did not differ on cognitive reappraisal. Findings suggest the key role of PTSD above and beyond trauma exposure, depression, and anxiety in specific aspects of emotion dysregulation among OIF/OEF/OND veterans. Interventions that help veterans expand and diversify their emotion regulation skills may serve as helpful adjunctive treatments for PTSD among OIF/OEF/OND veterans.

Background: Posttraumatic growth (PTG) is increasingly recognized as an important psychosocial phenomenon, but few studies have evaluated the longitudinal course of PTG. This study identified courses of PTG over a 2-year period in a contemporary, nationally representative sample of U.S. military veterans, and examined sociodemographic, military, trauma, medical, and psychosocial predictors of PTG course., Methods: Data were based on a Web-based survey of a nationally representative sample of 1,838 U.S. veterans who reported at least one potentially traumatic event and provided data at two time points (October-December 2011 and September-October 2013)., Results: Five different courses of PTG were identified--Consistently Low (33.6%), Moderately Declining (19.4%), Increasing PTG (16.8%), Dramatically Declining (15.7%), and Consistently High (14.5%). More than half (59.4%) of veterans who reported at least "moderate" PTG maintained that level of PTG 2 years later. Posttraumatic stress disorder symptoms, medical conditions, purpose in life, altruism, gratitude, religiosity, and an active reading lifestyle predicted maintenance or increase in PTG., Conclusions: PTG has a heterogeneous course and is not only common, but can persist over time especially in the presence of posttraumatic stress and certain psychosocial factors. Clinicians and researchers should consider the personal growth that can result from trauma and help trauma survivors find ways to maintain this growth over time., (© 2015 Wiley Periodicals, Inc.)

In this manuscript we systematically reviewed 29 articles from 2010 to 2014 that addressed the association between borderline personality disorder (BPD) and intimate partner violence (IPV) perpetration, with particular attention paid to the role of perpetrator sex. Our primary objective was to provide a summary of (1) the operationalization and measurement of BPD and IPV, (2) mechanisms of the BPD-IPV association, and (3)the current understanding of the role of perpetrator sex related to BPD and IPV. We observed three distinct operational definitions of BPD which are measured in a variety of ways. IPV measurement tends to be more consistent. Further, emotion perception, impulsivity, attachment, and substance use are proposed mechanisms to explain the BPD IPV relation. The findings regarding potential perpetrator sex differences in the BPD-IPV association are mixed. Finally, we also provide recommendations for future research and clinical practice.

Within exposure-based trauma treatments for posttraumatic stress disorder (PTSD), imagery vividness during imaginal exposure of the traumatic memory is an understudied but potentially important predictor of treatment outcome. Further, to our knowledge, this relationship has only been studied in women to date, and never among individuals with PTSD and substance use disorders which could impact ability to produce vivid mental imagery and its impact. The current study investigated whether imagery vividness ratings during in-session exposure predicted post-treatment PTSD symptom severity in a sample of men and women with comorbid PTSD and substance use disorders, and also examined whether gender moderated this relationship. A sample of 71 participants who received an exposure-based trauma treatment were included in the analyses. PTSD symptom severity was assessed using both the Clinician Administered PTSD Scale (CAPS) and the Impact of Event Scale-Revised (IES-R). Results varied according to method of assessing PTSD symptom severity. Higher imagery vividness was associated with better treatment outcome when assessed by the CAPS, with vividness in later sessions relating more strongly to outcome than vividness in earlier sessions. With the IES-R, higher imagery vividness ratings predicted more favorable treatment outcome for men, but less favorable treatment outcomes for women. Findings are discussed in the context of using imagery vividness to maximize treatment outcomes and future research directions involving scientific replication., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Individuals with posttraumatic stress disorder (PTSD) exhibit deficits in cognitive and emotional processes. PTSD severity is positively associated with anxiety sensitivity (AS) and difficulties in emotion regulation, and difficulties in emotion regulation mediate the relation between AS and PTSD. However, previous research has not examined the interactive nature of these variables. Associations between PTSD, AS, and difficulties in emotion regulation were examined in patients with PTSD in a residential substance treatment program (N = 120). Conditional process analyses indicated an interactive effect of difficulties in emotion regulation and AS for predicting PTSD symptom severity. For individuals high in emotion regulation difficulties, PTSD symptom severity was high regardless of level of AS; conversely, for individuals high in AS, increased PTSD severity was observed regardless of level of emotion regulation difficulties. Results suggest directions for future research, including targeting patient specific cognitive-affective processes to enhance PTSD treatment response among substance dependent individuals.