Co-occurring Chronic Pain and PTSD Among US Military Veterans: Prevalence, Correlates, and Functioning.

BACKGROUND: The prevalence of co-occurring chronic pain and posttraumatic stress disorder (PTSD) has yet to be established in a nationally representative sample of US veterans, and little is known about the individual contributing roles of these disorders to the psychiatric and functional burden of this comorbidity. OBJECTIVE: To determine the prevalence of chronic pain, PTSD, and co-occurring chronic pain and PTSD, and psychiatric comorbidities and psychosocial functioning in these groups. DESIGN: Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of US veterans. PARTICIPANTS: Veterans (n=4069) were classified into four groups: control (i.e., no PTSD or chronic pain), chronic pain only, PTSD only, and co-occurring chronic pain and PTSD. MAIN MEASURES: A probable PTSD diagnosis was established using the PTSD Checklist for DSM-5, and a chronic pain diagnosis using a self-report item that queried health care professional diagnoses. Psychiatric and functional status were assessed using the Patient Health Questionnaire-4, Alcohol Use Disorders Identification Test, Screen of Drug Use, Suicide Behaviors Questionnaire-Revised, Short Form Health Survey-8, Brief Inventory of Psychosocial Functioning, and Medical Outcomes Study Cognitive Functioning Scale. KEY RESULTS: A total of 3.8% of veterans reported both probable PTSD and a diagnosis of chronic pain. Relative to veterans with chronic pain alone, those with co-occurring chronic pain and probable PTSD were more likely to screen positive for psychiatric disorders (odds ratios [ORs]=2.59-9.88) and scored lower on measures of psychosocial functioning (Cohen's ds=0.38-1.43). Relative to veterans with probable PTSD only, those with co-occurring chronic pain and probable PTSD were more likely to have attempted suicide (OR=4.79; 95%CI, 1.81-12.69). CONCLUSIONS: Results underscore the importance of whole health care that considers a broad range of health and functional domains in the assessment and treatment of co-occurring chronic pain and PTSD in veterans.

Psychological Burden of Systemic Racism-Related Distress in New York City Healthcare Workers During the COVID-19 Pandemic.

BACKGROUND: Little is known about the relationship among systemic racism, psychological symptoms (depression, anxiety, and/or post-traumatic stress disorders), and burnout in healthcare workers (HCWs). OBJECTIVE: To determine whether distress related to awareness of systemic racism contributes to psychological symptoms and/or burnout in HCWs. We explored whether this form of racism-related distress may moderate the relationship between race, ethnicity, psychological symptoms, and burnout. DESIGN: A cross-sectional survey was conducted from November 19, 2020, through January 11, 2021. Statistical analysis was conducted from May 3, 2022, to June 15, 2022. PARTICIPANTS: Frontline HCWs at an urban tertiary care hospital in New York City. MAIN MEASURES: Distress related to awareness of systemic racism (SR) and racial disparities in COVID-19 outcomes (RD), psychological symptoms, and burnout. KEY RESULTS: Two thousand one of 4654 HCWs completed the survey (response rate 43.0%). Most HCWs reported experiencing distress related to awareness of systemic racism (1329 [66.4%]) and to racial disparities in COVID-19 outcomes (1137 [56.8%]). Non-Hispanic Black participants (SR odds ratio (OR) 2.84, p < .001; RD OR 2.34, p < .001), women (SR OR 1.35, p = .01; RD OR 1.67, p < .001), and those with history of mental illness (SR OR 2.13, p < .001; RD OR 1.66, p < .001) were more likely to report SR- and RD-related distress, respectively. HCWs who experienced "quite-a-bit to extreme" SR-related distress were more likely to screen positive for psychological symptoms (OR 5.90, p < .001) and burnout (OR 2.26, p < .001). CONCLUSIONS: Our findings suggest that distress related to awareness of systemic racism, not race/ethnicity, was associated with experiencing psychological symptoms and burnout in HCWs. As the medical community continues to critically examine the role of systemic racism in healthcare, our work is a first step in characterizing its toll on the psychological well-being of HCWs.

Genetic and non-genetic predictors of risk for opioid dependence.

BACKGROUND: Elucidation of the interaction of biological and psychosocial/environmental factors on opioid dependence (OD) risk can inform our understanding of the etiology of OD. We examined the role of psychosocial/environmental factors in moderating polygenic risk for opioid use disorder (OUD). METHODS: Data from 1958 European ancestry adults who participated in the Yale-Penn 3 study were analyzed. Polygenic risk scores (PRS) were based on a large-scale multi-trait analysis of genome-wide association studies (MTAG) of OUD. RESULTS: A total of 420 (21.1%) individuals had a lifetime diagnosis of OD. OUD PRS were positively associated with OD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.21-1.66). Household income and education were the strongest correlates of OD. Among individuals with higher OUD PRS, those with higher education level had lower odds of OD (OR 0.92, 95% CI 0.85-0.98); and those with posttraumatic stress disorder (PTSD) were more likely to have OD relative to those without PTSD (OR 1.56, 95% CI 1.04-2.35). CONCLUSIONS: Results suggest an interplay between genetics and psychosocial environment in contributing to OD risk. While PRS alone do not yet have useful clinical predictive utility, psychosocial factors may help enhance prediction. These findings could inform more targeted clinical and policy interventions to help address this public health crisis.

Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals.

BACKGROUND: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. METHODS: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. RESULTS: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. CONCLUSIONS: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

Structural inequities contribute to racial/ethnic differences in neurophysiological tone, but not threat reactivity, after trauma exposure.

Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.

Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure.

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.

Posttraumatic stress disorder and insomnia in US military veterans: Prevalence, correlates, and psychiatric and functional burden.

Military veterans have high rates of psychiatric conditions such as posttraumatic stress disorder, which can complicate the clinical management of insomnia. Population-based data are lacking on the prevalence, characteristics and mental health burden of veterans with co-occurring posttraumatic stress disorder and insomnia. The current cross-sectional study analysed data from a nationally representative sample of 4069 US veterans examining the prevalence and comorbidity between posttraumatic stress disorder and insomnia, and their associations with psychiatric and medical comorbidities, suicidality, and psychosocial functioning. Results revealed that 4.0% of US veterans screened positive for posttraumatic stress disorder + insomnia, 7.4% for insomnia only, and 3.2% for posttraumatic stress disorder only. Compared with controls, higher odds of major depressive disorder and generalized anxiety disorder were observed in the posttraumatic stress disorder + insomnia and posttraumatic stress disorder only groups. Moreover, compared with the control group, posttraumatic stress disorder + insomnia and posttraumatic stress disorder only groups had higher odds of current suicidal ideation, while the posttraumatic stress disorder + insomnia group had also higher odds of attempting suicide. Relative to the posttraumatic stress disorder only group, the posttraumatic stress disorder + insomnia group scored substantially lower on measures of cognitive, emotional and social functioning (d = 1.05, 1.04 and 0.87, respectively). This study provides contemporary data regarding current prevalence, correlates, and psychiatric and functional burden of posttraumatic stress disorder + insomnia among US veterans. The results underscore the importance of assessing, monitoring and treating posttraumatic stress disorder and insomnia as part of the efforts to mitigate suicide risk and promote multi-domain functioning in this population.

Negative aging stereotypes in U.S. military veterans: results from the National Health and Resilience in Veterans Study.

U.S. military veterans are an average 20 years older than non-veterans and have elevated rates of certain health conditions. While negative aging stereotypes have been linked to increased risk for various health conditions, little is known about the prevalence and correlates of these stereotypes in this population. Using data from a nationally representative sample of 4,069 U.S. veterans surveyed between 11/19 and 3/20, we examined (1) the current prevalence of negative aging stereotypes related to physical, mental, and cognitive health and (2) sociodemographic, health, and psychosocial factors associated with these stereotypes. Multivariable regression and relative weight analyses were conducted to identify independent correlates of negative aging stereotypes. Results revealed that 82.3%, 71.1%, and 30.0% of veterans endorsed negative aging stereotypes related to physical, cognitive, and emotional health, respectively. Older age (36.6% relative variance explained), grit (23.6%), and optimism (17.5%) explained the majority of the variance in negative age stereotypes related to physical aging; grit (46.6%), openness to experiences (31.5%), and older age (15.1%) in negative age stereotypes related to cognitive aging; and emotional stability (28.8%), purpose in life (28.8%), and grit (25.3%) in negative age stereotypes related to emotional aging. This study provides an up-to-date characterization of the prevalence and correlates of negative aging stereotypes in U.S. veterans. Results underscore the importance of targeting key correlates of negative aging stereotypes, such as lower grit, as part of efforts to promote health and functioning in this population.

Well-Being Domains in U.S. Military Veterans: Identifying Modifiable Factors to Promote Whole Health.

The U.S. Department of Veterans Affairs is actively transitioning away from a disease-centric model of healthcare to one that prioritizes disease prevention and the promotion of overall health and well-being. Described as Whole Health, this initiative aims to provide personalized, values-centered care that optimizes physical, behavioral, spiritual, and socioeconomic well-being. To inform this initiative, we analyzed cross-sectional data from a nationally representative sample of primarily older U.S. military veterans to estimate levels of well-being across these domains, and identify sociodemographic, military, and potentially modifiable health and psychosocial correlates of them. Results revealed that, overall, veterans reported high domain-specific well-being (average scores ranging from 6.7 to 8.3 out of 10), with the highest levels in the socioeconomic domain and lowest in the physical domain. Several modifiable factors, including purpose in life, resilience, and social support, were strongly associated with the examined well-being domains. Interventions targeting these constructs may help promote well-being among U.S. veterans.

Using the Moral Injury and Distress Scale to identify clinically meaningful moral injury.

Despite the proliferation of moral injury studies, a remaining gap is distinguishing moral injury from normative distress following exposure to potentially morally injurious events (PMIEs). Our goal was to leverage mental health and functional measures to identify clinically meaningful and functionally impairing moral injury using the Moral Injury and Distress Scale (MIDS). Participants who endorsed PMIE exposure (N = 645) were drawn from a population-based sample of military veterans, health care workers, and first responders. Using signal detection methods, we identified the optimally efficient MIDS score for detecting clinically significant posttraumatic stress and depressive symptom severity, trauma-related guilt, and functional impairment. The most efficient cut scores across outcomes converged between 24 and 27. We recommend a cut score of 27 given that roughly 70% of participants who screened positive on the MIDS at this threshold reported clinically significant mental health symptoms, and approximately 50% reported severe trauma-related guilt and/or functional impairment. Overall, 10.2% of respondents exposed to a PMIE screened positive for moral injury at this threshold, particularly those who identified as a member of a minoritized racial or ethnic group (17.9%) relative to those who identified as White, non-Hispanic (8.0%), aOR = 2.52, 95% CI [1.45, 4.42]. This is the first known study to establish a cut score indicative of clinically meaningful and impairing moral injury. Such scores may enhance clinicians' abilities to conduct measurement-based moral injury care by enabling them to identify individuals at risk of negative outcomes and better understand risk and protective factors for moral injury.

Barriers to Mental Health Care in US Military Veterans.

BACKGROUND: Military veterans often encounter multiple obstacles to mental health care, such as stigma, practical barriers (e.g., high cost), and negative beliefs about mental health care. To date, however, nationally representative data on the prevalence and key correlates of these barriers to care are lacking. Such data are critical to informing population-based efforts to reduce barriers and promote engagement in mental health treatment in this population. METHODS: Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed 4,069 US veterans, 531 (weighted 15.0%) of whom screened positive for a mental disorder but never received mental health treatment. Multivariable logistic regression and relative importance analyses were conducted to identify key predisposing, enabling, and need-based factors associated with endorsement of stigma, instrumental barriers, and negative beliefs about mental health care. RESULTS: A total 47.1% of veterans endorsed any barrier to care, with 38.7% endorsing instrumental barriers to care, 28.8% perceived stigma, and 22.0% negative beliefs about mental health care. Lower purpose in life, grit, and received social support were most consistently associated with these barriers to care. CONCLUSIONS: Nearly half of US veterans with psychiatric need and no history of mental health treatment report barriers to care. Modifiable characteristics such as a low purpose in life, grit, and received support were associated with endorsement of these barriers. Results may help inform resource allocation, as well as prevention, psychoeducation, and treatment efforts to help reduce barriers and promote engagement with mental health services in this population.

Problematic Alcohol Use Trajectories in U.S. Military Veterans during a Public Health Crisis: Results from a 3-year, Nationally Representative, Longitudinal Study.

A growing number of studies have examined alcohol use during the COVID-19 pandemic. However, few longitudinal studies evaluated the prevalence and correlates of different trajectories of problematic alcohol use in vulnerable segments of the population, such as US veterans, over the 3-year course of the COVID-19 pandemic. Data were analyzed from the National Health and Resilience in Veterans Study, a nationally representative, longitudinal study of 2,441 US veterans. Latent growth mixture modeling was used to identify the trajectories and correlates of problematic alcohol use. Four trajectories were identified: consistent (N = 170, weighted 7.2%), decreasing (N = 38, weighted 2.2%), increasing (N = 22, weighted 1.2%), and low (N = 2,211, weighted 89.4%) problematic alcohol use. Greater household income, pre-pandemic drug use disorder (DUD), lower social support, and COVID-19 infection to self or non-household members were associated with an increasing relative to decreasing problematic alcohol use trajectory. Greater household income, adverse childhood experiences (ACEs), pre-pandemic DUD, lower social support, and greater COVID-related social restriction stress were associated with an increasing relative to a low problematic alcohol use trajectory. Younger age, male sex, ACEs, pre-pandemic DUD, lower pre-pandemic and greater decline in protective psychosocial characteristics, COVID-19 infection to non-household member, and lower COVID-related financial stress were associated with a consistent relative to a low problematic alcohol use trajectory. Overall, pre-pandemic greater income, DUD, and lower social support were associated with an increase in problematic alcohol use among US veterans during the COVID-19 pandemic. Results may help inform prevention efforts to mitigate problematic alcohol use during prolonged crises in this population.

Posttraumatic Growth in U.S. Military Veterans: Results from the National Health and Resilience in Veterans Study.

Despite increasing recognition that positive psychological changes or posttraumatic growth (PTG) may develop after highly stressful or traumatic events, contemporary population-based data on the epidemiology of PTG in high-risk samples such as U.S. military veterans are lacking. Additionally, in light of emerging evidence suggesting an 8-factor model of posttraumatic stress disorder (PTSD) symptoms, an up-to-date characterization of how these symptom clusters relate to PTG can help inform efforts to help promote PTG. Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study (NHRVS), which surveyed a nationally representative sample of 3,847 trauma-exposed U.S. veterans. Participants completed assessments of potentially traumatic events, PTSD symptoms, and PTG, as well as a broad range of sociodemographic, military, trauma, health, personality, and psychosocial characteristics. Results revealed that 63.2% of trauma-exposed veterans and 86.4% of veterans who screened positive for PTSD endorsed moderate-or-greater PTG; these prevalences are higher than those reported in an independent U.S. veteran sample in 2011 (50.1% and 72.0%, respectively). An inverted U-shaped association was observed between PTSD symptom severity and PTG levels, with scores of 31 to 51 on the PTSD Checklist for DSM-5 associated with the highest likelihood of PTG. Intrinsic religiosity and internally- and externally-generated intrusive symptoms of PTSD were identified as the strongest correlates of PTG. Results suggest that prevention and treatment efforts to mitigate severe PTSD symptoms, and help promote intrinsic religiosity, and more deliberate and organized rumination about traumatic experiences may help foster PTG in veterans.

The mediating role of social support in associations between childhood adversity, military sexual trauma, and homelessness in a nationally representative sample of US veterans.

Among veterans, availability of social support and histories of military sexual trauma (MST) and/or adverse childhood experiences (ACEs) are particularly salient correlates of homelessness. Using path analyses, we investigated whether social support (i.e., interpersonal social support and community integration) would at least partially account for the relationships of MST and ACEs with any lifetime homelessness in a large, nationally representative sample of veterans (N = 4069, 9.8% female). Interpersonal social support and community integration partially explained the relationship between ACEs and any lifetime homelessness. However, they did not mediate the relationship between MST and any lifetime homelessness. Female veterans also reported higher trauma rates and lower perceived social support than male counterparts during correlational analyses. These results reinforce existing literature on the importance of research and interventions tailored to veterans with low social support and integration. Results have potential to inform interventions and policy for veterans experiencing and/or at risk for homelessness.

Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms.

Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of Fear Potentiated Startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal.Significance StatementAlterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on non-trauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk.

Prevalence, correlates, and mental health burden associated with homelessness in U.S. military veterans.

BACKGROUND: Homelessness is a major public health problem among U.S. military veterans. However, contemporary, population-based data on the prevalence, correlates, and mental health burden of homelessness among veterans are lacking. METHODS: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, a nationally representative survey of veterans (n = 4069). Analyses examined the prevalence and correlates of homelessness, as well as the independent associations between homelessness and current probable psychiatric conditions, suicidality, and functioning. RESULTS: The lifetime prevalence of homelessness was 10.2% (95% confidence interval 9.3-11.2). More than 8-of-10 veterans reported experiencing their first episode of homelessness following military service, with a mean of 10.6 years post-discharge until onset (s.d. = 12.6). Adverse childhood experiences (ACEs), cumulative trauma burden, current household income, younger age, and drug use disorder emerged as the strongest correlates of homelessness (49% of total explained variance). Veterans with a history of homelessness had elevated odds of lifetime suicide attempt, attempting suicide two or more times, and past-year suicide ideation [odd ratios (ORs) 1.3-3.1]. They also had higher rates of current probable posttraumatic stress disorder, major depressive, generalized anxiety, and drug use disorders (ORs 1.7-2.4); and scored lower on measures of mental, physical, cognitive, psychosocial functioning (d = 0.11-0.15). CONCLUSIONS: One in ten U.S. veterans has experienced homelessness, and these veterans represent a subpopulation at substantially heightened risk for poor mental health and suicide. ACEs were the strongest factor associated with homelessness, thus underscoring the importance of targeting early childhood adversities and their mental health consequences in prevention efforts for homelessness in this population.

Moral injury and substance use disorders among US combat veterans: results from the 2019-2020 National Health and Resilience in Veterans Study.

BACKGROUND: Exposure to potentially morally injurious events (PMIEs) is associated with increased risk for substance use disorders (SUDs), although population-based studies remain limited. The goal of this study was to better understand the relationships between PMIE exposure and lifetime and past-year alcohol use disorder (AUD), drug use disorder (DUD), and SUD. METHODS: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 1321 combat veterans. Multivariable analyses examined associations between three types of PMIE exposure (perpetration, witnessing, and betrayal), and lifetime and past-year AUD, DUD, and SUD, adjusting for sociodemographic variables, combat exposure severity, prior trauma, and lifetime posttraumatic stress disorder and major depressive disorder. RESULTS: Perpetration was associated with increased odds of lifetime AUD (OR 1.15; 95% CI 1.01-1.31) and lifetime SUD (OR 1.18; 95% CI 1.03-1.35). Witnessing was associated with greater odds of past-year DUD (OR 1.20; 95% CI 1.04-1.38) and past-year SUD (OR 1.14; 95% CI 1.02-1.28). Betrayal was associated with past-year AUD (OR 1.20; 95% CI 1.03-1.39). A large proportion of the variance in past-year AUD was accounted for by betrayal (38.7%), while witnessing accounted for 25.8% of the variance in past-year DUD. CONCLUSIONS: Exposure to PMIEs may be a stronger contributor to SUDs among veterans than previously known. These findings highlight the importance of targeted assessment and treatment of moral injury among veterans with SUDs, as well as attending to specific types of morally injurious experiences when conceptualizing and planning care.

Mental health impact of the COVID-19 pandemic in U.S. military veterans: a population-based, prospective cohort study.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has caused myriad health, social, and economic stressors. To date, however, no known study has examined changes in mental health during the pandemic in the U.S. military veteran population. METHODS: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, a nationally representative, prospective cohort survey of 3078 veterans. Pre-to-peri-pandemic changes in psychiatric symptoms were evaluated, as well as pre-pandemic risk and protective factors and pandemic-related correlates of increased psychiatric distress. RESULTS: The prevalence of generalized anxiety disorder (GAD) positive screens increased from pre- to peri-pandemic (7.1% to 9.4%; p < 0.001) and was driven by an increase among veterans aged 45-64 years (8.2% to 13.5%; p < 0.001), but the prevalence of major depressive disorder and posttraumatic stress disorder positive screens remained stable. Using a continuous measure of psychiatric distress, an estimated 13.2% of veterans reported a clinically meaningful pre-to-peri-pandemic increase in distress (mean = 1.1 standard deviation). Veterans with a larger pre-pandemic social network size and secure attachment style were less likely to experience increased distress, whereas veterans reporting more pre-pandemic loneliness were more likely to experience increased distress. Concerns about pandemic-related social losses, mental health COVID-19 effects, and housing stability during the pandemic were associated with increased distress, over-and-above pre-pandemic factors. CONCLUSIONS: Although most U.S. veterans showed resilience to mental health problems nearly 1 year into the pandemic, the prevalence of GAD positive screens increased, particularly among middle-aged veterans, and one of seven veterans experienced increased distress. Clinical implications of these findings are discussed.

Positive personality traits moderate persistent high alcohol consumption, determined by polygenic risk in U.S. military veterans: results from a 10-year, population-based, observational cohort study.

BACKGROUND: Understanding the interplay between psychosocial factors and polygenic risk scores (PRS) may help elucidate the biopsychosocial etiology of high alcohol consumption (HAC). This study examined the psychosocial moderators of HAC, determined by polygenic risk in a 10-year longitudinal study of US military veterans. We hypothesized that positive psychosocial traits (e.g. social support, personality traits, optimism, gratitude) may buffer risk of HAC in veterans with greater polygenic liability for alcohol consumption (AC). METHODS: Data were analyzed from 1323 European-American US veterans who participated in the National Health and Resilience in Veterans Study, a 10-year, nationally representative longitudinal study of US military veterans. PRS reflecting genome-wide risk for AC (AUDIT-C) was derived from a Million Veteran Program genome-wide association study (N = 200 680). RESULTS: Among the total sample, 328 (weighted 24.8%) had persistent HAC, 131 (weighted 9.9%) had new-onset HAC, 44 (weighted 3.3%) had remitted HAC, and 820 (weighted 62.0%) had no/low AC over the 10-year study period. AUDIT-C PRS was positively associated with persistent HAC relative to no/low AC [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI) = 1.23-1.67] and remitted HAC (RRR = 1.63, 95% CI = 1.07-2.50). Among veterans with higher AUDIT-C PRS, greater baseline levels of agreeableness and greater dispositional gratitude were inversely associated with persistent HAC. CONCLUSIONS: AUDIT-C PRS was prospectively associated with persistent HAC over a 10-year period, and agreeableness and dispositional gratitude moderated this association. Clinical interventions designed to target these modifiable psychological traits may help mitigate risk of persistent HAC in veterans with greater polygenic liability for persistent HAC.

Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden.

BACKGROUND: Little is known about environmental factors that may influence associations between genetic liability to suicidality and suicidal behavior. METHODS: This study examined whether a suicidality polygenic risk score (PRS) derived from a large genome-wide association study (N = 122,935) was associated with suicide attempts in a population-based sample of European-American US military veterans (N = 1664; 92.5% male), and whether cumulative lifetime trauma exposure moderated this association. RESULTS: Eighty-five veterans (weighted 6.3%) reported a history of suicide attempt. After adjusting for sociodemographic and psychiatric characteristics, suicidality PRS was associated with lifetime suicide attempt (odds ratio 2.65; 95% CI 1.37-5.11). A significant suicidality PRS-by-trauma exposure interaction emerged, such that veterans with higher levels of suicidality PRS and greater trauma burden had the highest probability of lifetime suicide attempt (16.6%), whereas the probability of attempts was substantially lower among those with high suicidality PRS and low trauma exposure (1.4%). The PRS-by-trauma interaction effect was enriched for genes implicated in cellular and developmental processes, and nervous system development, with variants annotated to the DAB2 and SPNS2 genes, which are implicated in inflammatory processes. Drug repurposing analyses revealed upregulation of suicide gene-sets in the context of medrysone, a drug targeting chronic inflammation, and clofibrate, a triacylglyceride level lowering agent. CONCLUSION: Results suggest that genetic liability to suicidality is associated with increased risk of suicide attempt among veterans, particularly in the presence of high levels of cumulative trauma exposure. Additional research is warranted to investigate whether incorporation of genomic information may improve suicide prediction models.