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The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

Military veterans are at high risk for nicotine dependence. This clinical demonstration project used invitational letters, referral to the National Cancer Institute's Smoking Quitline, and local Veteran Affairs prescriptions for tobacco cessation to evaluate whether this low-cost method would potentially reduce smoking in separated veterans who served in Afghanistan and Iraq. Three cohorts (500 each) of recently separated veterans from Afghanistan and Iraq were contacted by survey letters. Interested veterans received follow-up telephone calls using standardized scripts. They were referred to the National Cancer Institute's Smoking Quitline (1-877-44U-QUIT) and offered local Veteran Affairs pharmacologic treatment for smoking cessation. Forty-three percent of respondents who were smokers were interested in the clinical program; of these, 77% participated. At 2 months follow-up, 38% of participants self-reported maintained smoking abstinence. Results suggested that the intervention was feasible and assisted the small number of veterans who participated. [ABSTRACT FROM AUTHOR]

Two hundred and forty-one Vietnam combat veterans with chronic posttraumatic stress disorder (PTSD) completed measures of PTSD symptom severity, combat exposure, depression, hostility, interpersonal violence, substance abuse, and arrest history. The majority of veterans with PTSD (63%) reported being arrested at least once after returning from Vietnam. Logistic regression analyses indicated that PTSD severity was positively correlated with arrest history even when other variables associated with criminal behavior were taken into account. Recommendations for evaluation and treatment of individuals with PTSD who are at risk of becoming involved with the criminal justice system are discussed. [ABSTRACT FROM AUTHOR]

Research has yet to examine the relationship between financial well-being and community reintegration of veterans. To address this, we analyzed data from n = 1,388 Iraq and Afghanistan War Era Veterans who completed a national survey on postdeployment adjustment. The results indicated that probable major depressive disorder, posttraumatic stress disorder, and traumatic brain injury were associated with financial difficulties. However, regardless of diagnosis, veterans who reported having money to cover basic needs were significantly less likely to have postdeployment adjustment problems such as criminal arrest, homelessness, substance abuse, suicidal behavior, and aggression. Statistical analyses also indicated that poor money management (e.g., incurring significant debt or writing bad checks) was related to maladjustment, even among veterans at higher income levels. Given these findings, efforts aimed at enhancing financial literacy and promoting meaningful employment may have promise to enhance outcomes and improve quality of life among returning veterans. [ABSTRACT FROM AUTHOR]

Background: Sickle cell disease (SCD) is a chronic medical condition characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, and subsequently, end-organ damage and reduced survival. Because of this significant pathophysiology and early mortality, we hypothesized that patients with SCD are experiencing accelerated biological aging compared with individuals without SCD., Methods: We utilized the DunedinPACE measure to compare the epigenetic pace of aging in 131 Black Americans with SCD to 1391 Black American veterans without SCD., Results: SCD patients displayed a significantly accelerated pace of aging (DunedinPACE mean difference of 0.057 points) compared with the veterans without SCD, whereby SCD patients were aging ≈0.7 months more per year than those without SCD (p = 4.49 × 10-8). This was true, even though the SCD patients were significantly younger according to chronological age than the individuals without SCD, making the epigenetic aging discrepancy even more apparent. This association became stronger when we removed individuals with posttraumatic stress disorder from the non-SCD group (p = 2.18 × 10-9), and stronger still when we restricted the SCD patients to those with hemoglobin SS and Sβ0 thalassemia genotypes (p = 1.61 × 10-10)., Conclusions: These data support our hypothesis that individuals with SCD experience accelerated biological aging as measured by global epigenetic variation. The assessment of epigenetic measures of biological aging may prove useful to identify which SCD patients would most benefit from clinical interventions to reduce mortality., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Importance: Cognitive behavioral therapy for insomnia (CBTi) is the standard of care for treating insomnia disorder, but access is limited. Alternative approaches are needed to expand access to the standard of care., Objective: To examine the effectiveness of a nurse-supported, self-directed behavioral insomnia intervention for decreasing insomnia severity and improving sleep outcomes among veterans, a population with considerable mental health comorbidity., Design, Setting, and Participants: This randomized clinical trial included 178 patients with insomnia disorder who were recruited from a Veterans Affairs hospital (Durham VA Healthcare System) from September 2019 to April 2022 and randomized following baseline assessment; follow-ups were conducted at 8 weeks (primary end point) and 6 months. Data analysis was primarily conducted during the summer of 2023 and concluded in May 2024., Intervention: Six weekly phone calls from a nurse interventionist plus assigned treatment manual readings covering CBTi treatment components. The health education manual focused on health topics but not sleep., Main Outcomes and Measures: The primary outcome was the Insomnia Severity Index (score range, 0-28; remission <8; differential improvement of 3 points targeted) score assessed at 8 weeks postrandomization. Secondary outcomes were sleep outcomes, depression, fatigue, treatment response, and remission., Results: Of 178 study participants, the mean (SD) age was 55.1 (13.2) years, and 128 (71.9%) identified as men. At 8 weeks, Insomnia Severity Index scores decreased by an estimated mean (SE) of 5.7 (0.51) points in the intervention group and 2.0 (0.47) points in the control group, a differential mean improvement of 3.7 points (95% CI, -5.0 to -2.4; P < .001). Differences were sustained at 6 months (mean, -2.8; 95% CI, -4.4 to -1.3; P < .001). The intervention also resulted in greater improvements at 8 weeks postrandomization in diary sleep onset latency, wake after sleep onset, and sleep efficiency and actigraphy sleep efficiency; these differences were sustained at 6 months. At 8 weeks, depression and fatigue were significantly reduced, and the odds of treatment response and remission were greater in the intervention group compared with controls., Conclusions and Relevance: This randomized clinical trial found that despite greater prevalence of mental health conditions and sleep difficulties among veterans, a nurse-supported self-directed CBTi was more effective than health education control for reducing insomnia severity and improving sleep outcomes. Although less effective than therapist-delivered CBTi, findings were comparable with other trials using modified CBTi protocols., Trial Registration: ClinicalTrials.gov Identifier: NCT03727438.

Background: Nearly 2 million U.S. veterans live with co-occurring alcohol use disorder and posttraumatic stress disorder (AUD/PTSD). Extant AUD/PTSD treatments emphasize symptom reduction, sometimes overlooking psychosocial functioning improvements, and have dropout rates as high as 50 %. Additionally, current approaches to measuring psychosocial functioning are limited to self-report. This study protocol describes a 1:1 parallel, two-arm, pilot randomized controlled trial comparing Behavioral Activation (BA) psychotherapy to Relapse Prevention (RP) psychotherapy for veterans with AUD/PTSD., Methods: Forty-six veterans with AUD/PTSD will be block-randomized to eight weekly, virtual, hour-long individual sessions of BA or RP. Clinical interview, self-report, and geospatial assessments will be administered at pre- and post-treatment. Select outcome and exploratory measures will be administered during treatment. Analyses will focus on trial feasibility, BA acceptability, and preliminary efficacy. Geospatial analyses will explore whether pre- to post-treatment changes in geospatial movement can be used to objectively measure treatment response. The study site and an independent Data and Safety Monitoring Board will monitor trial progress, safety, and quality. De-identified data from consenting participants will be submitted to a sponsor-designated data repository., Conclusion: If successful, this trial could help to provide veterans with AUD/PTSD with a more acceptable treatment option. Positive findings would also lay groundwork for testing BA in civilians with AUD/PTSD. Finally, by incorporating novel geospatial methods and technologies, this study could potentially yield a new approach to objectively measuring AUD/PTSD recovery that could be used in other clinical trials. This study was registered in ClinicalTrials.gov (NCT06249386)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Epigenetic measures of aging derived from DNA methylation are promising biomarkers associated with prospective morbidity and mortality, but require validation in real-world medical settings. Using data from 2,216 post-9/11 veterans, we examined whether accelerated DunedinPACE aging scores were associated with chronic disease morbidity, predicted healthcare costs, and mortality assessed over an average of 13.1 years of follow up in VA electronic health records. Veterans with faster DunedinPACE aging scores developed more chronic disease and showed larger increases in predicted healthcare costs over the subsequent 5, 10, and 15 years. Faster aging was associated with incident myocardial infarction, stroke, diabetes, cancer, liver disease, and renal disease, as well greater risk of mortality due to all-causes and chronic disease. These findings provide evidence that accelerated epigenetic aging is associated with worsening prospective health across multiple chronic diseases and organ systems assessed using electronic health records from an integrated healthcare system., Competing Interests: Conflicts of interest: Drs. Terrie Moffitt, Avshalom Caspi, and Karen Sugden are named as an inventor on a license issued by Duke University for the DunedinPACE. The algorithm to calculate DunedinPACE is publicly available on Github, https://github.com/danbelsky/DunedinPACE. No other authors have conflicts of interest to report.

Genome-wide association studies (GWAS) identify genetic variants underlying complex traits but are limited by stringent genome-wide significance thresholds. We present GRIN (Gene set Refinement through Interacting Networks), which increases confidence in the expanded gene set by retaining genes strongly connected by biological networks when GWAS thresholds are relaxed. GRIN was validated on both simulated interrelated gene sets as well as multiple GWAS traits. From multiple GWAS summary statistics of suicide attempt, a complex phenotype, GRIN identified additional genes that replicated across independent cohorts and retained biologically interrelated genes despite a relaxed significance threshold. We present a conceptual model of how these retained genes interact through neurobiological pathways that may influence suicidal behavior, and identify existing drugs associated with these pathways that would not have been identified under traditional GWAS thresholds. We demonstrate GRIN's utility in boosting GWAS results by increasing the number of true positive genes identified from GWAS results., (© 2024. The Author(s).)

Tobacco-related deaths remain the leading cause of preventable death in the United States. Veterans suffering from posttraumatic stress disorder (PTSD)-about 11% of those receiving care from the Department of Veterans Affairs (VA)-have triple the risk of developing tobacco use disorder (TUD). The most efficacious strategies being used at the VA for smoking cessation only result in a 23% abstinence rate, and veterans with PTSD only achieve a 4.5% abstinence rate. Therefore, there is a critical need to develop more effective treatments for smoking cessation. Recent studies suggest the insula is integrally involved in the neurocircuitry of TUD. Thus, we propose a feasibility phase II randomized controlled trial (RCT) to study a form of repetitive transcranial magnetic stimulation (rTMS) called intermittent theta burst stimulation (iTBS). iTBS has the advantage of allowing for a patterned form of stimulation delivery that we will administer at 90% of the subject's resting motor threshold (rMT) applied over a region in the right post-central gyrus most functionally connected to the right posterior insula. We hypothesize that by increasing functional connectivity between the right post-central gyrus and the right posterior insula, withdrawal symptoms and short-term smoking cessation outcomes will improve. Fifty eligible veterans with comorbid TUD and PTSD will be randomly assigned to active-iTBS + cognitive behavioral therapy (CBT) + nicotine replacement therapy (NRT) (n = 25) or sham-iTBS + CBT + NRT (n = 25). The primary outcome, feasibility, will be determined by achieving a recruitment of 50 participants and retention rate of 80%. The success of iTBS will be evaluated through self-reported nicotine use, cravings, withdrawal symptoms, and abstinence following quit date (confirmed by bioverification) along with evaluation for target engagement through neuroimaging changes, specifically connectivity differences between the insula and other regions of interest., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Military sexual assault (MSA) is a prevalent issue among military personnel that has been linked to adverse mental and physical health outcomes, including posttraumatic stress disorder (PTSD) and suicidal thoughts and behaviors. The present study sought to investigate the relationship between MSA and nonsuicidal self-injury (NSSI) in a national sample of Gulf War-I Era U.S. veterans. The study analyzed data from 1,153 Gulf War-I veterans collected through a cross-sectional survey that assessed demographic information, clinical outcomes, military background, and history of MSA and NSSI. MSA was found to be significantly associated with NSSI at the bivariate level ( OR  = 2.19, p < .001). Further, MSA remained significantly associated with NSSI ( AOR  = 2.50, p = .002) after controlling for relevant demographics and clinical outcomes. Veterans with a history of MSA were approximately two and half times more likely to engage in NSSI than veterans who had not experienced MSA. The present findings provide preliminary evidence linking MSA and NSSI. Further, the findings highlight the importance of assessing MSA and NSSI in veteran populations, particularly among those seeking treatment for PTSD.

Objectives: Cognitive processing therapy (CPT) is an evidence-based psychotherapy for posttraumatic stress disorder (PTSD); however, little is known about how interrelationships between PTSD symptoms change over the course of treatment. The current study examined baseline, midtreatment, and posttreatment PTSD symptom networks during CPT for PTSD., Method: Adults with PTSD ( n = 107) received 12 sessions of CPT as part of a randomized trial. Self-reported PTSD symptoms were assessed at pretreatment, midtreatment, and posttreatment, and network analysis was used to examine the interrelationships between symptoms at these three timepoints. Linear regression was conducted to examine whether any baseline symptoms or midpoint symptoms predicted overall treatment change., Results: In the baseline PTSD network, feelings of detachment and feeling upset at reminders of the trauma were central to the symptom network. These symptoms were no longer central at midtreatment, possibly suggesting that CPT quickly reduces the importance of these symptoms. These findings were consistent with regression results that, after accounting for multiple comparisons, high baseline scores of feeling upset at trauma reminders predicted later treatment change. At the conclusion of treatment, strong negative emotions were the most central symptom and may be most important in maintaining or lowering other PTSD symptoms at the conclusion of treatment., Conclusions: Though replication is necessary, these findings offer insights into identifying which symptoms may be most predictive of treatment outcomes and the course by which CPT reduces PTSD symptoms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Persons diagnosed with schizophrenia (SCZ) or bipolar I disorder (BPI) are at high risk for self-injurious behavior, suicidal ideation, and suicidal behaviors (SB). Characterizing associations between diagnosed health problems, prior pharmacological treatments, and polygenic scores (PGS) has potential to inform risk stratification. We examined self-reported SB and ideation using the Columbia Suicide Severity Rating Scale (C-SSRS) among 3,942 SCZ and 5,414 BPI patients receiving care within the Veterans Health Administration (VHA). These cross-sectional data were integrated with electronic health records (EHRs), and compared across lifetime diagnoses, treatment histories, follow-up screenings, and mortality data. PGS were constructed using available genomic data for related traits. Genome-wide association studies were performed to identify and prioritize specific loci. Only 20% of the veterans who reported SB had a corroborating ICD-9/10 EHR code. Among those without prior SB, more than 20% reported new-onset SB at follow-up. SB were associated with a range of additional clinical diagnoses, and with treatment with specific classes of psychotropic medications (e.g., antidepressants, antipsychotics, etc.). PGS for externalizing behaviors, smoking initiation, suicide attempt, and major depressive disorder were associated with SB. The GWAS for SB yielded no significant loci. Among individuals with a diagnosed mental illness, self-reported SB were strongly associated with clinical variables across several EHR domains. Analyses point to sequelae of substance-related and psychiatric comorbidities as strong correlates of prior and subsequent SB. Nonetheless, past SB was frequently not documented in health records, underscoring the value of regular screening with direct, in-person assessments, especially among high-risk individuals., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at multiple CpG loci across the genome. Moreover, these effects can be shared or specific to both central and peripheral tissues. Here, we aim to identify blood DNAm differences associated with PTSD and characterize the underlying biological mechanisms by examining the extent to which they mirror associations across multiple brain regions., Methods: As the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup, we conducted the largest cross-sectional meta-analysis of epigenome-wide association studies (EWASs) of PTSD to date, involving 5077 participants (2156 PTSD cases and 2921 trauma-exposed controls) from 23 civilian and military studies. PTSD diagnosis assessments were harmonized following the standardized guidelines established by the PGC-PTSD Workgroup. DNAm was assayed from blood using either Illumina HumanMethylation450 or MethylationEPIC (850K) BeadChips. A common QC pipeline was applied. Within each cohort, DNA methylation was regressed on PTSD, sex (if applicable), age, blood cell proportions, and ancestry. An inverse variance-weighted meta-analysis was performed. We conducted replication analyses in tissue from multiple brain regions, neuronal nuclei, and a cellular model of prolonged stress., Results: We identified 11 CpG sites associated with PTSD in the overall meta-analysis (1.44e-09 < p < 5.30e-08), as well as 14 associated in analyses of specific strata (military vs civilian cohort, sex, and ancestry), including CpGs in AHRR and CDC42BPB . Many of these loci exhibit blood-brain correlation in methylation levels and cross-tissue associations with PTSD in multiple brain regions. Methylation at most CpGs correlated with their annotated gene expression levels., Conclusions: This study identifies 11 PTSD-associated CpGs, also leverages data from postmortem brain samples, GWAS, and genome-wide expression data to interpret the biology underlying these associations and prioritize genes whose regulation differs in those with PTSD., Competing Interests: Competing interests CYC is an employee of Biogen. NPD has served on scientific advisory boards for BioVie Pharma, Circular Genomics and Sentio Solutions for unrelated work. NRN serves as an unpaid member of the Ilumivu advisory board. SAMR receives support from the Wounded Warrior Project (WWP), Department of Veterans Affairs (VA), National Institute of Health (NIH), McCormick Foundation, Tonix Pharmaceuticals, Woodruff Foundation, and Department of Defense (DOD). Dr. Rauch receives royalties from Oxford University Press and American. KJR serves as a consultant for Acer, Bionomics, and Jazz Pharma; SABs for Sage, Boehringer Ingelheim, and Senseye. DJS has received consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda and Vistagen. MBS has in the past 3 years received consulting income from Acadia Pharmaceuticals, Aptinyx, atai Life Sciences, BigHealth, Biogen, Bionomics, BioXcel Therapeutics, Boehringer Ingelheim, Clexio, Delix Therapeutics, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, NeuroTrauma Sciences, PureTech Health, Sage Therapeutics, Sumitomo Pharma, and Roche/Genentech. MBS has stock options in Oxeia Biopharmaceuticals and EpiVario. MBS has been paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). MBS has also received research support from NIH, Department of Veterans Affairs, and the Department of Defense. MBS is on the scientific advisory board for the Brain and Behavior Research Foundation and the Anxiety and Depression Association of America.

Objectives: Obstructive sleep apnea (OSA) among veterans is frequently underdiagnosed and undertreated. The present study sought to: 1) characterize the prevalence and rate of treatment of OSA among VA users and non-users and 2) examine the associations between diagnosed or probable OSA and key physical and mental health outcomes., Methods: Gulf-War I-era Veterans were recruited as part of a national survey assessing mental and physical health concerns, healthcare needs, and healthcare utilization. OSA diagnoses were self-reported while sleep apnea risk was assessed via the STOP-Bang. Veterans also completed questionnaires assessing overall health, pain, depression, PTSD, and psychosocial functioning., Results: 1,153 veterans were included in the present analyses (Mean age = 58.81; 21.84% female). Compared to non-VA healthcare users, veterans receiving care at the VA were more likely to have been diagnosed with OSA ( p  < .001) and report receiving treatment for OSA ( p  = .005). Compared to veterans at low risk for OSA, veterans at elevated risk reported higher levels of pain ( p  = .001), depression ( p  = .02), and poorer psychosocial functioning ( p  < .001)., Conclusions: OSA diagnoses appear to be more common among VA healthcare users. Findings suggest that OSA remains underdiagnosed and associated with important physical and mental health consequences. Additional screening for OSA, especially among non-VA clinics, is warranted.

Introduction: Research indicates that being married is associated with reduced risk of suicide and self-directed violence (SDV) relative to being divorced. Simultaneously, difficulties within relationships predict poorer health outcomes. However, research on relationship status rarely examines relationship functioning, obfuscating the joint contribution of these variables for SDV risk., Method: Veterans ( N  = 1,049) completed a survey that included assessment of relationship status, relationship functioning, and SDV history. Logistic regression models tested how (a) relationship status, (b) relationship dysfunction, and (c) being divorced compared to being in a low- or high-dysfunction relationship were associated with SDV, controlling for several intrapersonal risk factors., Results: Veterans in a relationship did not differ in SDV history compared to divorced/separated veterans. However, more dysfunction within relationships was associated with greater odds of a history of SDV and suicidal cognitions. Finally, SDV histories were more likely among veterans endorsing high-dysfunction relationships compared with (a) low-dysfunction relationships and (b) divorced veterans., Conclusion: It may be insufficient to only consider relationship status when evaluating interpersonal risk factors for SDV. A single item assessing relationship dysfunction was associated with enacted SDV and suicidal cognitions over and above intrapersonal risk factors. Integrating such single-item measures into clinical practice could improve identification and subsequent tailored intervention for veterans at greater risk for SDV.

Prior research has established the psychometric properties of the Critical Warzone Experiences (CWE) scale among post-9/11 Iraq/Afghanistan-era veterans; however, the psychometric properties of the CWE among Gulf War I-era veterans have not yet been established. The first objective of the present study was to examine the psychometric properties of the CWE among Gulf War I-era veterans. The second objective was to test the hypothesis that the CWE would have a significant indirect effect on suicidal thoughts and behaviors via posttraumatic stress disorder (PTSD) and depressive symptoms. To test these hypotheses, a survey packet that included the CWE and measures of PTSD symptoms, depressive symptoms, and suicidal thoughts and behaviors was administered to 1,153 Gulf War I-era veterans. Consistent with prior research in post-9/11 Iraq/Afghanistan-era veterans, the CWE exhibited good internal consistency (α = .85), a unidimensional factor structure (RMSEA = .056, CFI = .959, SRMR = .033; average factor loading = .69), and good concurrent validity with PTSD ( r  = .47, p  < .001) and depressive ( r  = .31, p  < .001) symptoms among Gulf War I-era veterans. Additionally, as hypothesized, a significant indirect effect from the CWE to suicidal thoughts and behaviors via PTSD and depressive symptoms (β = .35, p  < .001) was also observed. Taken together, our findings provide strong support for using the CWE with Gulf War I-era veterans.

Measures of epigenetic aging derived from DNA methylation (DNAm) have enabled the assessment of biological aging in new populations and cohorts. In the present study, we used an epigenetic measure of aging, DunedinPACE, to examine rates of aging across demographic groups in a sample of 2,309 United States military veterans from the VISN 6 MIRECC's Post-Deployment Mental Health Study. As assessed by DunedinPACE, female veterans were aging faster than male veterans (β = 0.39, 95 % CI [0.29, 0.48], p < .001), non-Hispanic Black veterans were aging faster than non-Hispanic White veterans (β = 0.58, 95 % CI [0.50, 0.66], p < .001), and older veterans were biologically aging faster than younger veterans (β = 0.21, 95 % CI [0.18, 0.25], p < .001). In secondary analyses, these differences in rates of aging were not explained by a variety of biopsychosocial covariates. In addition, the percentage of European genetic admixture in non-Hispanic Black veterans was not associated with DunedinPACE. Our findings suggest that female and non-Hispanic Black veterans are at greater risk of accelerated aging among post-9/11 veterans. Interventions that slow aging might provide relatively greater benefit among veterans comprising these at-risk groups., Competing Interests: Declaration of competing interest None of the authors have conflicts of interest to report., (Published by Elsevier B.V.)

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Alcohol use disorder (AUD) is prevalent among veterans, and excessive alcohol use is associated with significant mental and physical health consequences. Currently, the largest cohort of veterans seeking services at the VA are those from the 1990s Gulf War Era. This cohort of veterans is unique due to the nature of their deployment resulting in a myriad of unexplained symptoms collectively known as "Gulf War Illness" and higher rates of mental health problems. The present study sought to examine the association between probable AUD and mental health treatment utilization in a sample of 1126 (882 male) Gulf War-era veterans., Methods: Veterans completed a self-report survey including the AUDIT-C, questions about mental health treatment engagement, and demographic questions., Results: Results demonstrated that approximately 20 % of the sample screened positive for probable AUD, determined by standard AUDIT-C cutoff scores. Among those screening positive for AUD, 25 % reported engaging in mental health treatment in the past year. Veterans with probable AUD who use VA care had 3.8 times the odds of receiving mental health services than veterans not using VA care. Use of mental health services was associated with mental health comorbidity and identifying as Black/African American., Conclusions: The results of the present study highlight a significant unmet need for mental health treatment among Gulf War-era veterans with AUD., Competing Interests: Declaration of competing interest The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the United States Government or the Department of Veterans Affairs. The authors have no other conflicts of interest or other disclosures to disclose., (Published by Elsevier Inc.)

Background: Posttraumatic stress disorder (PTSD) has been associated with ischemic heart disease in women veterans, but evidence for associations with other cardiovascular disorders remains limited in this population. This retrospective longitudinal cohort study evaluated the association of PTSD with incident stroke/transient ischemic attack (TIA) in women veterans., Methods and Results: Veterans Health Administration electronic health records were used to identify women veterans aged ≥18 years engaged with Veterans Health Administration health care from January 1, 2000 to December 31, 2019. We identified women veterans with and without PTSD without a history of stroke or TIA at start of follow-up. Propensity score matching was used to match groups on age, race or ethnicity, traditional cardiovascular risk factors, female-specific risk factors, a range of mental and physical health conditions, and number of prior health care visits. PTSD, stroke, TIA, and risk factors used in propensity score matching were based on diagnostic codes. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for associations of PTSD with an incident stroke/TIA composite. Subanalyses considered stroke and TIA separately, plus age- and race- or ethnicity-stratified analyses were carried out. The analytic sample included 208 092 women veterans (104 046 with and 104 046 without PTSD). PTSD was associated with a greater rate of developing stroke/TIA (HR, 1.33 [95% CI, 1.25-1.42], P <0.001). This elevated risk was especially pronounced in women <50 years old and in Hispanic/Latina women., Conclusions: Findings indicate a strong association of PTSD with incident stroke/TIA in women veterans. Research is needed to determine whether addressing PTSD and its downstream consequences can offset this risk.

Cannabis use has been increasing over the past decade, not only in the general US population, but particularly among military veterans. With this rise in use has come a concomitant increase in cannabis use disorder (CUD) among veterans. Here, we performed an epigenome-wide association study for lifetime CUD in an Iraq/Afghanistan era veteran cohort enriched for posttraumatic stress disorder (PTSD) comprising 2,310 total subjects (1,109 non-Hispanic black and 1,201 non-Hispanic white). We also investigated CUD interactions with current PTSD status and examined potential indirect effects of DNA methylation (DNAm) on the relationship between CUD and psychiatric diagnoses. Four CpGs were associated with lifetime CUD, even after controlling for the effects of current smoking (AHRR cg05575921, LINC00299 cg23079012, VWA7 cg22112841, and FAM70A cg08760398). Importantly, cg05575921, a CpG strongly linked to smoking, remained associated with lifetime CUD even when restricting the analysis to veterans who reported never smoking cigarettes. Moreover, CUD interacted with current PTSD to affect cg05575921 and cg23079012 such that those with both CUD and PTSD displayed significantly lower DNAm compared to the other groups. Finally, we provide preliminary evidence that AHRR cg05575921 helps explain the association between CUD and any psychiatric diagnoses, specifically mood disorders., Competing Interests: Declaration of competing interest All authors report no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Recent findings indicate that firefighters may be at increased risk for death by suicide; however, there has been only limited suicide prevention work in fire service to date. Aim: The objective of this program evaluation project was to develop and evaluate a web-based Safety Planning Intervention (SPI) training course for firefighter peer support specialists. Method: Peer support specialists who completed the web-based SPI training were administered evaluation questionnaires before the training and then again at a 3-month follow-up assessment. Results: A total of 213 peer support specialists completed the SPI training. Most participants took 2-3 h to complete the training. Participants generally reported high levels of satisfaction with the course, with the vast majority (94.4%) indicating they would recommend it to their peers. Course completers also demonstrated significant gains in SPI knowledge and self-efficacy from baseline to 3-month follow-up (all p 's < .001). Moreover, the percentage of participants who reported completing a safety plan with someone they suspected at being of risk for suicide increased approximately 7-fold from baseline (3.5%) to 3-month follow-up (25.2%; p < .001). Participants further reported that 97.6% of the safety plans that they completed resulted in a positive outcome. Limitations: This was a program evaluation project that did not include a control group. Thus, causality cannot be inferred. Conclusions: The present findings suggest that web-based SPI training is a feasible and scalable approach for training peer support specialists to deliver the SPI to at-risk individuals.

Importance: Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans' health, such as suicide-related behaviors and substance use disorders (SUDs)., Objective: To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP)., Design, Setting, and Participants: A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the African, European, and Hispanic or Latin American ancestries. Next, a conditional PheWAS, covarying for PGSs of comorbid psychiatric problems (depression, schizophrenia, and suicide attempt; European ancestries only), was performed. Lastly, to adjust for unmeasured confounders, a within-family analysis of significant associations from the main PheWAS was performed in full siblings (European ancestries only). This study included the electronic health record data from US veterans from VA health care centers enrolled in MVP. Analyses took place from February 2022 to August 2023 covering a period from October 1999 to January 2020., Exposures: PGSs for EXT, depression, schizophrenia, and suicide attempt., Main Outcomes and Measures: Phecodes for diagnoses derived from the International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification, codes from electronic health records., Results: Within the MVP (560 824 patients; mean [SD] age, 67.9 [14.3] years; 512 593 male [91.4%]), the EXT PGS was associated with 619 outcomes, of which 188 were independent of risk for comorbid problems or PGSs (from odds ratio [OR], 1.02; 95% CI, 1.01-1.03 for overweight/obesity to OR, 1.44; 95% CI, 1.42-1.47 for viral hepatitis C). Of the significant outcomes, 73 (11.9%) were significant in the African results and 26 (4.5%) were significant in the Hispanic or Latin American results. Within-family analyses uncovered robust associations between EXT PGS and consequences of SUDs, including liver disease, chronic airway obstruction, and viral hepatitis C., Conclusions and Relevance: Results of this cohort study suggest a shared polygenic basis of EXT disorders, independent of risk for other psychiatric problems. In addition, this study found associations between EXT PGS and diagnoses related to SUDs and their sequelae. Overall, this study highlighted the potential negative consequences of EXT disorders for health and functioning in the US veteran population.

We present an ensemble transfer learning method to predict suicide from Veterans Affairs (VA) electronic medical records (EMR). A diverse set of base models was trained to predict a binary outcome constructed from reported suicide, suicide attempt, and overdose diagnoses with varying choices of study design and prediction methodology. Each model used twenty cross-sectional and 190 longitudinal variables observed in eight time intervals covering 7.5 years prior to the time of prediction. Ensembles of seven base models were created and fine-tuned with ten variables expected to change with study design and outcome definition in order to predict suicide and combined outcome in a prospective cohort. The ensemble models achieved c-statistics of 0.73 on 2-year suicide risk and 0.83 on the combined outcome when predicting on a prospective cohort of [Formula: see text] 4.2 M veterans. The ensembles rely on nonlinear base models trained using a matched retrospective nested case-control (Rcc) study cohort and show good calibration across a diversity of subgroups, including risk strata, age, sex, race, and level of healthcare utilization. In addition, a linear Rcc base model provided a rich set of biological predictors, including indicators of suicide, substance use disorder, mental health diagnoses and treatments, hypoxia and vascular damage, and demographics., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

People who experience trauma and develop posttraumatic stress disorder (PTSD) are at increased risk for poor health. One mechanism that could explain this risk is accelerated biological aging, which is associated with the accumulation of chronic diseases, disability, and premature mortality. Using data from 2309 post-9/11 United States military veterans who participated in the VISN 6 MIRECC's Post-Deployment Mental Health Study, we tested whether PTSD and trauma exposure were associated with accelerated rate of biological aging, assessed using a validated DNA methylation (DNAm) measure of epigenetic aging-DunedinPACE. Veterans with current PTSD were aging faster than those who did not have current PTSD, β = 0.18, 95% CI [0.11, 0.27], p < .001. This effect represented an additional 0.4 months of biological aging each year. Veterans were also aging faster if they reported more PTSD symptoms, β = 0.13, 95% CI [0.09, 0.16], p < 0.001, or higher levels of trauma exposure, β = 0.09, 95% CI [0.05, 0.13], p < 0.001. Notably, veterans with past PTSD were aging more slowly than those with current PTSD, β = -0.21, 95% CI [-0.35, -0.07], p = .003. All reported results accounted for age, gender, self-reported race/ethnicity, and education, and remained when controlling for smoking. Our findings suggest that an accelerated rate of biological aging could help explain how PTSD contributes to poor health and highlights the potential benefits of providing efficacious treatment to populations at increased risk of trauma and PTSD., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Nonsuicidal self-injury (NSSI) is a robust predictor of suicide attempts. However, understanding of NSSI and associated treatment utilization among Veterans is limited. Although impairment may be assumed, few studies examine the association between NSSI and psychosocial functioning, a core component of the rehabilitation framework of mental health. In a national survey of Veterans, current NSSI ( n  = 88) was associated with higher rates of suicidal thoughts and behaviors and more severe psychosocial impairment after adjusting for demographics and probable diagnoses of posttraumatic stress disorder, major depressive disorder, and alcohol use disorder, compared to Veterans without NSSI ( n  = 979). Only half of Veterans with NSSI were engaged with mental health services, with few appointments attended, suggesting that these Veterans are not receiving treatment interventions. Results underscore the adverse outcomes associated with NSSI. Underutilization of mental health services highlights the importance of screening for NSSI among Veterans to improve psychosocial outcomes.

Many interventions for cannabis use disorder (CUD) are associated with decreases in frequency and quantity of use but fail to increase overall rates of sustained abstinence. It is currently unknown whether reductions in use (in the absence of sustained abstinence) result in clinically significant improvements in functioning. The objective of this study was to refine a mobile contingency management approach to reduce cannabis use to ultimately evaluate whether reductions in frequency and quantity of cannabis are related to improvements in functional and mental health status. Three cohorts of participants (n = 18 total, n = 10 women) were enrolled and completed 2 weeks of ecological momentary assessment (EMA) during a baseline ad lib cannabis use period, followed by a 6-week reduction period. Participants completed EMA assessments multiple times per day and were prompted to provide videotaped saliva cannabis testing 2-3 times daily. Data from participants who were at least 80% adherent to all EMA prompts were analyzed (13 out of 18). During the ad lib phase, participants were using cannabis on 94% of the days and reported using a mean of 1.42 grams daily. The intervention was a mobile application that participants used to record cannabis use by saliva tests to bioverify abstinence and participants completed electronic diaries to report their grams used. During the 6-week intervention phase, participants reported reducing their use days to 47% of the days with a reported mean of .61 grams daily. In the last cohort, at least 50% of the heavy users were able to reduce their cannabis use by at least 50%. The effect of cannabis reduction (versus abstinence) is largely unknown. Observations suggest that it is possible to develop a mobile intervention to reduce cannabis use among heavy users, and this paradigm can be utilized in future work to evaluate whether reductions in cannabis use among heavy users will result in improvements in functional and mental health status., (Copyright © 2023 Association for Behavioral and Cognitive Therapies. Published by Elsevier Ltd. All rights reserved.)

Objective: Pain confers risk for suicidal thoughts and behaviors. Experiential avoidance (EA), which is relevant to both pain and suicide risk, has not been studied as a potential mechanism for this relationship. The present study tested the hypothesis that pain indirectly impacts suicide risk through EA in a national sample of Gulf War veterans., Methods: Participants included a stratified random sample of United States veterans ( N  = 1,012, 78% male) who had served in the Gulf War region between August 1990 and July 1991. Validated scales were used to quantify levels of pain, EA, and suicide risk., Results: Regression analyses indicated independent associations between pain, EA, and suicide risk; moreover, the association between pain and suicide risk was no longer significant once EA was included in model. Bootstrapping analyses confirmed that EA partially accounted for the cross-sectional association between pain and suicide risk, independent of common co-occurring problems, such as depression, PTSD, and alcohol use disorder symptoms., Conclusions: EA could be a key modifiable risk factor to target in people experiencing pain.

Objective: To apply deep neural networks (DNNs) to longitudinal EHR data in order to predict suicide attempt risk among veterans. Local explainability techniques were used to provide explanations for each prediction with the goal of ultimately improving outreach and intervention efforts., Materials and Methods: The DNNs fused demographic information with diagnostic, prescription, and procedure codes. Models were trained and tested on EHR data of approximately 500 000 US veterans: all veterans with recorded suicide attempts from April 1, 2005, through January 1, 2016, each paired with 5 veterans of the same age who did not attempt suicide. Shapley Additive Explanation (SHAP) values were calculated to provide explanations of DNN predictions., Results: The DNNs outperformed logistic and linear regression models in predicting suicide attempts. After adjusting for the sampling technique, the convolutional neural network (CNN) model achieved a positive predictive value (PPV) of 0.54 for suicide attempts within 12 months by veterans in the top 0.1% risk tier. Explainability methods identified meaningful subgroups of high-risk veterans as well as key determinants of suicide attempt risk at both the group and individual level., Discussion and Conclusion: The deep learning methods employed in the present study have the potential to significantly enhance existing suicide risk models for veterans. These methods can also provide important clues to explore the relative value of long-term and short-term intervention strategies. Furthermore, the explainability methods utilized here could also be used to communicate to clinicians the key features which increase specific veterans' risk for attempting suicide., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2023.)

Background: Post-traumatic stress disorder (PTSD) is associated with increased rates of incident ischemic heart disease (IHD) in women., Objectives: The purpose of this study was to determine mechanisms of the PTSD-IHD association in women., Methods: In this retrospective longitudinal cohort study, data were obtained from electronic health records of all U.S. women veterans who were enrolled in Veterans Health Administration care from January 1, 2000 to December 31, 2017. Propensity score matching was used to match women with PTSD to women without PTSD on age, number of prior Veterans Health Administration visits, and presence of various traditional and nontraditional cardiovascular risk factors at index visit. Cox regression was used to model time until incident IHD diagnosis (ie, coronary artery disease, angina, or myocardial infarction) as a function of PTSD and potential mediating risk factors. Diagnoses of IHD, PTSD, and risk factors were defined by International Classification of Diseases-9th or -10th Revision, and/or Current Procedural Terminology codes., Results: PTSD was associated with elevated rates of developing each risk factor. Traditional risk factors (hypertension, hyperlipidemia, smoking, diabetes) accounted for 24.2% of the PTSD-IHD association, psychiatric risk factors (eg, depression, anxiety, substance use disorders) accounted for 33.8% of the association, and all 13 risk factors accounted for 48.5% of the association., Conclusions: Traditional IHD risk factors explained a quarter of the PTSD-IHD association in women veterans, and over half of the risk of IHD associated with PTSD remained unexplained even when adjusting for a wide range of risk factors. To be actionable, factors underlying the remaining PTSD-IHD association warrant timely investigation., Competing Interests: This research was funded through a grant from the 10.13039/100000005Department of Defense U.S. Army Medical Research and Material Command Congressionally Directed Medical Research Programs (Ebrahimi; PR171210). The project was also supported by VA North Texas Health Care system, the 10.13039/100017544VA Greater Los Angeles Healthcare System, and Northport and Durham VA Medical Centers. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Nonsuicidal self-injury (NSSI) is a debilitating concern among U.S. veterans, with wall/object-punching commonly endorsed as an NSSI method. We examined how this behavior relates to other NSSI methods and psychosocial outcomes. We conducted a latent class analysis (LCA) of NSSI methods among 1,138 Gulf War Era veterans, (77.9% male), 21.7% of whom endorsed lifetime NSSI. We categorized classes based on their associations with age, sex, combat and military sexual assault exposure, then examined the association of class membership with psychosocial indicators. LCA results supported four classes: 1) High punching/banging NSSI (2.5%); 2) Multimethod NSSI methods (6.3%); 3) High-risk, multimethod NSSI (3.1%); and 4) Low-risk NSSI (88.1%). Psychosocial indicators (suicide attempt, ideation, possible depressive or posttraumatic stress disorders, poor psychosocial functioning) were worse for members of the NSSI classes versus those in the low-risk group. A subset of U.S. veterans may engage in NSSI primarily via punching/banging methods. All patterns of NSSI engagement were associated with negative psychosocial outcomes relative to those in the low-risk class of the behavior., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Importance: Cardiovascular disease (CVD) remains the leading cause of death in the US. Women veterans have higher rates of CVD compared with civilian US women; however, analyses of recent trends in mortality from cardiac disease for women veterans are lacking., Objective: To investigate trends in cardiac disease mortality among women veterans over approximately the past 2 decades and compare rates with those for civilian women., Design, Setting, and Participants: In this retrospective longitudinal cohort study, US Veterans Health Administration (VHA) electronic health record data, linked with the National Death Index, were analyzed for CVD trends and rates of cardiac disease mortality among women veterans (aged 18 years or older) with VHA health care encounters from January 1, 2000, to December 31, 2017. These data were compared with a national cohort of civilian women (aged 15 years or older) in the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database, which provides cause-of-death data using death certificates for all US residents. The data analysis was performed between March 10, 2021, and November 28, 2022., Exposure: Cardiac disease mortality among women veterans and civilian women., Main Outcomes and Measures: Cardiac disease mortality was based on International Classification of Diseases, Tenth Revision diagnostic codes (I00-I09, I11, I13, and I20-I51 as defined by CDC WONDER). For women veterans and civilian women, crude and age-adjusted cardiac disease mortality rates (per 100 000 life-years) and 95% CIs were calculated, with the 2000 US general population as the reference for age-adjusted rates., Results: From 2000 to 2017, 817 912 women veterans engaged with VHA health care (mean [SD] age, 45.7 [17.1] years), and 19 022 cardiac disease deaths were identified (22.4% of total deaths). The crude and age-adjusted cardiac disease mortality rates, respectively, per 100 000 life-years were 200.2 (95% CI, 181.0-221.0) and 197.6 (95% CI, 175.2-222.0) in 2000 and 196.0 (95% CI, 186.1-206.4) and 208.1 (95% CI, 196.4-220.4) in 2017, reflecting stable crude rates and a 5.3% increase in age-adjusted rates. For civilian women, the crude and age-adjusted rates decreased over time from 320.7 (95% CI, 319.7-321.8) and 268.1 (95% CI, 267.3-269.0) in 2000 to 220.9 (95% CI, 220.1-221.7) and 164.7 (95% CI, 164.1-165.3) in 2017., Conclusions and Relevance: In this cohort study comparing women veterans and civilian women, cardiac disease mortality rates for women veterans did not exhibit the improvements seen for civilian women during the nearly 2-decade study period. Further research and actionable clinical interventions are warranted to improve cardiovascular care for women veterans, who represent the fastest growing group of patients within the VHA health care system.

Intro: Nonsuicidal self-injury (NSSI) is associated with marked functional impairment and is a robust predictor of suicide attempts. Prevalence rates of NSSI, and self-directed violence more broadly, are elevated among military veterans. Despite the inclusion of interpersonal difficulty in the diagnostic criteria for NSSI disorder, the relationship between interpersonal risk factors and NSSI is not well-characterized, especially among veterans. This ecological momentary assessment (EMA) study investigated the hypothesis that interpersonal stressors and associated distress would precede and predict NSSI urge and engagement-but not vice versa-via cross-lagged multilevel modeling., Method: Forty veterans with NSSI disorder completed a 28-day EMA protocol with three daily prompts assessing NSSI urges, NSSI engagement, the occurrence of interpersonal stressors, and associated subjective interpersonal distress., Results: Interpersonal stressors preceded and predicted subsequent NSSI urges, but not NSSI engagement, whereas subjective interpersonal distress preceded and predicted both NSSI urges and NSSI engagement., Conclusion: Results identified interpersonal stressors as a risk factor for NSSI urges, and interpersonal distress as a risk factor for both NSSI urges and NSSI engagement. Findings highlight the importance of temporally assessing interpersonal factors related to NSSI and suggest that interpersonal distress may be a modifiable risk factor for NSSI., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)

Introduction: Despite a recent global decrease in suicide rates, death by suicide has increased in the United States. It is therefore imperative to identify the risk factors associated with suicide attempts to combat this growing epidemic. In this study, we aim to identify potential risk factors of suicide attempt using geospatial features in an Artificial intelligence framework., Methods: We use iterative Random Forest, an explainable artificial intelligence method, to predict suicide attempts using data from the Million Veteran Program. This cohort incorporated 405,540 patients with 391,409 controls and 14,131 attempts. Our predictive model incorporates multiple climatic features at ZIP-code-level geospatial resolution. We additionally consider demographic features from the American Community Survey as well as the number of firearms and alcohol vendors per 10,000 people to assess the contributions of proximal environment, access to means, and restraint decrease to suicide attempts. In total 1,784 features were included in the predictive model., Results: Our results show that geographic areas with higher concentrations of married males living with spouses are predictive of lower rates of suicide attempts, whereas geographic areas where males are more likely to live alone and to rent housing are predictive of higher rates of suicide attempts. We also identified climatic features that were associated with suicide attempt risk by age group. Additionally, we observed that firearms and alcohol vendors were associated with increased risk for suicide attempts irrespective of the age group examined, but that their effects were small in comparison to the top features., Discussion: Taken together, our findings highlight the importance of social determinants and environmental factors in understanding suicide risk among veterans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (At least a portion of this work is authored by David W. Oslin, Jean C. Beckham and Nathan A. Kimbrel on behalf of the U.S. Government and as regards Dr Oslin, Dr. Beckham, Dr. Kimbrel and the U.S. Government, is not subject to copyright protection in the United States. Foreign and other copyrights may apply.)

Tobacco cessation is reduced in U.S. military veterans experiencing homelessness. Mobile contingency management (mCM) is a promising treatment for tobacco use among populations experiencing homelessness, but past CM studies have largely been small, have relied on in-person follow-up, and/or lacked long-term biochemically verified abstinence measures. Veterans who smoked and were experiencing homelessness (N = 127) were randomly assigned to mCM treatment (4 weeks of mCM, 5 weeks of telehealth counseling, and the option of 12 weeks of pharmacotherapy) or VA standard care (3 biweekly group sessions and clinically appropriate pharmacotherapy), and all participants were randomly assigned to a $100 longer-term financial incentive for abstinence at 3-month follow-up. Participants were followed at 3-, 6-, and 12-months post-randomization, with the a priori main outcome designated as biochemically verified prolonged abstinence (with lapses) at 6-month follow-up. At 6-months, participants in the mCM group were significantly more likely to meet criteria for prolonged abstinence ( OR  = 3.1). Across time points, veterans in the mCM group had twice the odds of prolonged abstinence as those in the standard care group. However, by the 12-month follow-up, there was no statistically significant group difference in abstinence. Cost-effectiveness analysis indicated a modest increase in cost ($1,133) associated with an increase of one quality-adjusted life year saved for the intervention compared to standard care. mCM is a cost-effective approach to smoking cessation among veterans experiencing homelessness. Considering waning potency of this and other tobacco cessation interventions at 12-month follow-up, it is crucial to implement strategies to sustain abstinence for individuals experiencing homelessness., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.