Design of a randomized clinical trial of brief couple therapy for PTSD augmented with intranasal oxytocin.

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.

Sources of Social Support and Trauma Recovery: Evidence for Bidirectional Associations from a Recently Trauma-Exposed Community Sample.

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.

Sustaining the collaborative chronic care model in outpatient mental health: a matrixed multiple case study.

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.

An examination of relationship satisfaction as a predictor of outcomes of brief couple therapy for posttraumatic stress disorder.

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, Mage = 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, ß = .199, whereas there was no change among those in the nondistressed range at baseline (n = 151), ß = .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.

Lived Experience-Led Research Agenda to Address Early Death in People With a Diagnosis of a Serious Mental Illness: A Consensus Statement.

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.

Clinical outcomes of veterans affairs residential PTSD treatment for PTSD and depressive symptoms: 1-year follow-up outcomes and gender differences.

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).

Pilot test of intranasal oxytocin as an enhancer of brief couples therapy for posttraumatic stress disorder.

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.

Comparative effectiveness of evidence-based psychotherapies for PTSD delivered in VA residential PTSD treatment.

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.

The impact of trauma-focused psychotherapy for posttraumatic stress disorder on interpersonal functioning: A systematic review and meta-analysis of randomized clinical trials.

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.

Benchmarking quality of life to posttraumatic stress disorder symptom changes in cognitive processing therapy.

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.

A systematic review and meta-analysis of individual and couple therapies for posttraumatic stress disorder: Clinical and intimate relationship outcomes.

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.

Risk and protective factors in relation to early mortality among people with serious mental illness: Perspectives of peer support specialists and service users.

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).

In vivo defensive behaviors, fear, and attention bias to physical and negative evaluation threats.

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.

Social cognitive mechanisms in healthcare worker resilience across time during the pandemic.

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.

Evidence-based posttraumatic stress disorder treatment in a community sample: Military-affiliated versus civilian patient outcomes.

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, Mdiff = 5.75, p = .003, and PHQ-9, Mdiff = 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.

Addressing co-occurring suicidal thoughts and behaviors and posttraumatic stress disorder in evidence-based psychotherapies for adults: A systematic review.

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.

Behavioral Epidemic of Loneliness in Older U.S. Military Veterans: Results From the 2019-2020 National Health and Resilience in Veterans Study.

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.

Attachment Style Moderates Polygenic Risk for Incident Posttraumatic Stress in U.S. Military Veterans: A 7-Year, Nationally Representative, Prospective Cohort Study.

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.