Genes in context: path to more precise risk prediction in psychiatry?

This guest editorial describes the importance of converging genetics and psychosocial epidemiology research methods to understand the biopsychosocial etiology of psychiatric phenotypes.

Loneliness Trajectories in U.S. Military Veterans: A 3-Year Longitudinal Study of Risk and Protective Factors.

OBJECTIVES: Loneliness is a significant public health concern associated with adverse mental and physical health outcomes in older adults. This study examined the nature and correlates of predominant loneliness trajectories in a nationally representative sample of older U.S. military veterans. METHODS: Participants included 2,441 veterans (mean age = 63, 8% female, 80% white) from the National Health and Resilience in Veterans Study, a 3-year longitudinal cohort study. Growth mixture modeling (GMM) was used to identify distinct trajectory classes of loneliness based on self-reported ratings. Multinomial logistic three-step regression analyses examined potential psychosocial risk and protective factors associated with loneliness trajectories. RESULTS: GMM revealed three distinct loneliness trajectories: Low-decreasing loneliness (61.2%), moderate-increasing loneliness (31.6%), and high-increasing loneliness (7.2%). Being married/partnered and perceiving greater purpose in life emerged as protective factors against elevated levels of loneliness. Worse cognitive functioning was a risk factor for the moderate-increasing loneliness trajectory, while greater psychological distress and more adverse childhood experiences were risk factors for the high-increasing loneliness trajectory. DISCUSSION: Nearly 40% of older U.S. veterans exhibited trajectories characterized by moderate to high levels of loneliness, with both groups showing increases over time. Targeted interventions that promote social connectedness, enhance purpose in life, and address mental health concerns and early life adversities may help mitigate the negative health consequences associated with chronic loneliness in this vulnerable population.

Posttraumatic Stress Disorder, Obesity, and Accelerated Epigenetic Aging Among US Military Veterans.

This cross-sectional study uses data from 1135 male, European-American US military veterans to assess whether risk and protective factors influenced associations between posttraumatic stress disorder and epigenetic age.

Prevalence, Correlates, and Burden of Subthreshold PTSD in US Veterans.

Objectives: To provide an up-to-date estimate of subthreshold posttraumatic stress disorder (PTSD) in US military veterans based on a recently proposed working case definition of subthreshold PTSD and identify sociodemographic, psychiatric, and functional correlates of subthreshold PTSD relative to full PTSD.Methods: Data were analyzed from a nationally representative sample of US veterans. Probable lifetime subthreshold PTSD was operationalized as self reported endorsement of a potentially traumatic event (Criterion A); any 2 or 3 PTSD symptom clusters (Criteria B-E); symptom duration of more than 1 month (Criterion F); and PTSD symptom-related distress or functional impairment (Criterion G).Results: The prevalence of lifetime full PTSD was 8.4% (95% CI, 7.2%-9.7%) and the prevalence of subthreshold PTSD was 3.9% (95% CI, 3.2%-4.8%). Subthreshold PTSD was associated with intermediately elevated odds of current and lifetime psychiatric disorders and clinical problems relative to veterans with no PTSD (adjusted odds ratios [OR] ranged from 1.7 for current alcohol use disorder and 3.3 for lifetime major depressive disorder [MDD]). Full PTSD was associated with even greater odds for most outcomes (OR ranges from 1.7 for current drug use disorder to 11.1 for lifetime MDD). Veterans with subthreshold PTSD reported intermediate-level reductions in mental, psychosocial, and cognitive functioning relative to veterans with no PTSD and full PTSD.Conclusions: Subthreshold PTSD is prevalent and associated with considerable psychiatric and functional distress/impairment among US veterans. Efforts to identify and treat veterans with subthreshold PTSD may lead to improvements in mental health and functioning in this population.

Successful Aging in US Veterans with Mental Disorders: Results From the National Health and Resilience in Veterans Study.

OBJECTIVES: To determine the prevalence and correlates of successful aging in US veterans who screened positive for current major depressive disorder (MDD), generalized anxiety disorder (GAD), and/or posttraumatic stress disorder (PTSD). METHODS: In a nationally representative sample of 475 US military veterans (mean age=58.3, SD=14.7; range 24-92) who screened positive for MDD, GAD, and/or PTSD, multivariable logistic regression and relative importance analyses were conducted to identify independent correlates of successful aging. RESULTS: One-in-five (20.6%) veterans rated themselves as aging successfully. Resilience and gratitude were the strongest positive correlates of successful aging, accounting for 38.1% and 32.4% of the explained variance, respectively. Greater somatic symptoms were the strongest negative correlate, accounting for 11.2% of the explained variance. Higher gratitude moderated the negative association between somatic symptoms and successful aging. CONCLUSIONS: Positive psychiatry interventions targeting psychosocial factors such as resilience and gratitude may help promote successful aging among US veterans with mental disorders.

Persistent distress related to systemic racism among black veterans in the United States.

BACKGROUND: Distress related to systemic racism in the public service and healthcare systems is linked to adverse mental health sequelae in racial and ethnic minority populations. Emerging research has found that distress related to racism may impact military veterans, an increasingly racially and ethnically diverse segment of the US population who are at increased risk of mental health problems relative to non-veterans. To date, however, no known study has examined longitudinal trends in distress related to systemic racism in this population. METHODS: A nationally representative sample of 2361 US military veterans completed a baseline assessment in 2020 and a 2-year follow-up in 2022. A multinomial logistic regression analysis was conducted to examine longitudinal courses and baseline predictors of systemic racism-related distress. RESULTS: Relative to the veterans with no racism-related distress, those who reported racism-related distress across the 2-year study period were older, more likely to be female, Black, or Hispanic, and to have completed college or higher education, and reported more lifetime traumas and stressors. Nearly 4-of-5 of Black veterans endorsed distress related to systemic racism over the 2-year study period. LIMITATIONS: Use of self-report and abbreviated measures of distress related to systemic racism. CONCLUSIONS: Results suggest that distress related to systemic racism may pose a significant emotional burden on subgroups of US veterans. They further underscore the importance of training clinicians to provide culturally-informed assessments and treatments for Black and other racial and ethnic minority veterans who bear the weight of racial discrimination.

Psychological Factors, Physical Conditions, and Functioning Among US Veterans.

This cross-sectional study examines the association of protective psychological characteristics with mental, psychosocial, cognitive, and physical functioning in military veterans.

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.

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.

Functional significance of posttraumatic growth in U.S. military veterans.

BACKGROUND: Although many studies indicate that individuals who have experienced a traumatic event can experience posttraumatic growth (PTG), some researchers have questioned the significance of PTG in associations with functioning. The role of PTG in functioning following trauma may be better elucidated by accounting for its joint effects with posttraumatic stress disorder (PTSD) symptoms. METHODS: Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 3847 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: PTG was independently and moderately associated with higher mental, cognitive, and psychosocial functioning, but not physical functioning. Results showed a similar pattern of findings when examining relations between subdomains of PTG and these aspects of functioning. Additionally, among veterans who screened positive for PTSD, those who endorsed PTG reported higher levels of mental, cognitive, and/or psychosocial functioning than those who did not endorse PTG. LIMITATIONS: Findings may be limited by the use of a cross-sectional design, retrospective self-reports of PTG, and a predominantly older white male veteran sample. CONCLUSION: Results provide support for the functional significance of PTG and highlight the importance of considering PTSD symptoms to better understand the role of PTG in functioning. Clinical interventions to foster PTG may help promote post-trauma functioning.

Problem Opioid Use Among US Military Veterans: Prevalence, Correlates, and Psychiatric Characteristics.

OBJECTIVE: Problem opioid use (POU) is a serious public health crisis in the United States. However, little research has examined the prevalence, correlates, and psychiatric characteristics of POU in vulnerable segments of the population, such as US military veterans. METHODS: Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 2441 US veterans. Multivariable logistic regression models were conducted to identify correlates and psychiatric correlates of POU (defined as a positive screen on the Tobacco, Alcohol, Prescription Medication, and Other Substance Use Tool). RESULTS: A total 3.0% (95% confidence interval, 2.0%-4.5%) of US veterans screened positive for POU. Black, non-Hispanic race/ethnicity (odds ratio [OR], 3.83), lifetime alcohol use disorder (OR, 3.38), major depressive disorder (MDD; OR, 2.52), greater number of medical conditions (OR, 1.15), and disability in instrumental activities of daily living (IADL); OR, 1.86) were independently associated with POU. A significant interaction between IADL disability and MDD was observed (OR, 10.73)-among veterans with IADL disability, those with MDD had more than 6-fold greater POU than those without MDD (20.6% vs 3.2%). Furthermore, POU was associated with 2- to 3-folds greater odds of current generalized anxiety disorder and current posttraumatic stress disorder, and lifetime suicide attempt. CONCLUSIONS: POU affects 3.0% of US veterans and is associated with Black race/ethnicity, lifetime physical and mental health morbidities, as well as current psychiatric disorders and lifetime suicide attempts. Results underscore the importance of assessing physical and mental health disorders in veterans at-risk for POU and addressing co-occurring psychiatric disorders associated with POU in this population.

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.

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.

Firearm storage practices among military veterans in the United States: Findings from a nationally representative survey.

BACKGROUND: Unsafe storage of firearms is associated with increased risk of suicide.. However, contemporary population-based data on the prevalence and correlates of firearm storage practices among veterans are limited. METHODS: Data were from the 2022 National Health and Resilience in Veterans Study, a nationally representative sample of 2441 veterans. Analyses examined: (1) the prevalence of firearm storage practices; (2) sociodemographic, psychiatric, and clinical characteristics associated with storing firearms loaded and/or in non-secure location; and (3) associations between types of potentially traumatic events and storage practices. RESULTS: More than half of veterans reported owning one or more personal firearms (50.9%). Among firearm owners, 52.9% reported some form of unsafe firearm storage practice (i.e., loaded and/or non-secure location), with 39.9% reporting that they stored one or more firearms loaded. After adjusting for sociodemographic characteristics, major depressive, alcohol and drug use disorders, direct trauma exposures, future suicidal intent, and traumatic brain injury were associated with storing firearms loaded and/or in a non-secure location (ORs = 1.09-7.16). Veterans with a history of specific forms of direct trauma exposure (e.g., physical assault) were more likely to store firearms unsafely. LIMITATIONS: Cross-sectional design precludes causal inference. CONCLUSIONS: Half of U.S. veterans who own firearms store at least one personal firearm loaded and/or in a non-secure location, with approximately four-in-ten keeping a loaded firearm in the home. These high rates underscore the importance of nationwide training initiatives to promote safe firearm storage for all service members and veterans, regardless of risk status, as well as for healthcare professionals working with veterans.

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.

Well-Being of US Military Veterans.

This survey study analyzed data from a nationally representative sample of US veterans to examine ratings and correlates of well-being.

Functional decline during the COVID-19 pandemic among U.S. military veterans: Results from the National Health and Resilience in Veterans Study.

OBJECTIVES: The coronavirus disease-2019 pandemic has contributed to widespread social and economic stressors, along with substantial health problems, including loss of life. To date, however, relatively few studies have examined the prevalence and correlates of declines in mental and physical functioning in U.S. military veterans, an older and potentially vulnerable segment of the U.S. adult population. METHODS: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, a nationally representative, longitudinal study of 3078 veterans. Veterans were surveyed prior to the pandemic (pre-pandemic) and 1 year later during the height of the pandemic (peri-pandemic). Multivariable analyses were conducted to identify risk and protective variables associated with pre-to-peri pandemic declines in self-reported physical and mental functioning. RESULTS: The prevalence of veterans who experienced functional decline (≥0.5 standard deviation reductions) pre-to-peri-pandemic was 18.1% (N = 541) for physical functioning and 18.3% (N = 547) for mental functioning. Older age, greater adverse childhood experiences (ACEs), and pandemic-related posttraumatic stress symptoms were the strongest correlates of physical functional decline, while greater ACEs, loneliness, pandemic-related posttraumatic and social restriction stress symptoms, and lower protective psychosocial characteristics were the strongest correlates of mental functional decline. CONCLUSIONS: Although the majority of U.S. Veterans showed functional maintenance or improvement 1 year into the pandemic, nearly one-in-five experienced a decline in physical or mental functioning. Results could help inform identification of veterans who may be at risk for functional decline during large-magnitude stressors, such as national or global pandemics.

Changes in mental health among U.S. military veterans during the COVID-19 pandemic: A network analysis.

Increases of symptoms of posttraumatic stress disorder (PTSD), anxiety and depression have been observed among individuals exposed to potentially traumatic events in the first months of the COVID-19 pandemic. Similarly, associations among different aspects of mental health, such as symptoms of PTSD and suicidal ideation, have also been documented. However, studies including an assessment prior to the onset and during the height of the pandemic are lacking. We investigated changes in symptoms of PTSD, depression, anxiety, suicidal ideation, and posttraumatic growth in a population-based sample of 1232 U.S. military veterans who experienced a potentially traumatic event during the first year of the pandemic. Symptoms were assessed prior to (fall/winter 2019) and one year into the pandemic (fall/winter 2020). We compared changes in symptom interrelations using network analysis, and assessed their associations with pandemic-related PTSD and posttraumatic growth symptoms. A subtle increase in psychopathological symptoms and a decrease in posttraumatic growth was observed one year into the pandemic. The peripandemic network was more densely connected, and pandemic-related PTSD symptoms were positively associated with age, anxiety, worst-event PTSD symptoms, and pandemic-related posttraumatic growth. Our findings highlight the resilience of veterans exposed to a potentially traumatic event during the first year of a pandemic. Similarly, the networks did not fundamentally change from prepandemic to one year into the pandemic. Despite this relative stability on a group level, individual reactions to potentially traumatic events could have varied substantially. Clinicians should individualize their assessments but be aware of the general resilience of most veterans.

Purpose in life protects against the development of suicidal thoughts and behaviors in U.S. veterans without a history of suicidality: A 10-year, nationally representative, longitudinal study.

OBJECTIVES: To determine the incidence of suicidal ideation and suicide attempts (STBs) in veterans without an endorsed history of STBs and identify baseline predictors of these outcomes over a 10-year period. METHODS: Population-based prospective cohort study of 2307 US military veterans using five waves of the 2011-2021 National Health and Resilience in Veterans Study. Baseline data were collected in 2011, with follow-up assessments conducted 2-(2013), 4-(2015), 7-(2018), and 10-years (2021) later. RESULTS: In total, 10.1 % (N = 203) of veterans endorsed incident suicidal ideation (SI) over the 10-year period and 3.0 % (N = 55) endorsed an incident suicide attempt (SA). Multivariable regression analyses revealed the following baseline predictors of incident SI: lower annual household income, current posttraumatic stress disorder, current alcohol use disorder (AUD), disability with activities of daily living (i.e., ADLs) or instrumental activities of daily living (i.e., IADLs), lower perceived social support, lower community integration, and lower purpose in life. Current AUD, greater cumulative trauma burden, and lower purpose in life at baseline were predictive of incident SA. Relative importance analyses revealed that lower purpose in life was the strongest predictor of both incident SI and SA. CONCLUSIONS: Psychosocial determinants of health, such as purpose in life, may be more reliable predictors of incident suicidal thoughts and behaviors than traditional risk factors (e.g., psychiatric distress; history of SA) in those without a history of STBs. Evidence-based interventions that facilitate purpose in life and feelings of connectedness and belonging should be examined as possible treatments for STBs.

Pandemic-related posttraumatic psychological growth in U.S. military veterans: A 3-year, nationally representative, longitudinal study.

Little is known about the positive psychological changes or posttraumatic growth (PTG) in response to the pandemic as the COVID-19 vaccines has become widely available. This longitudinal study aimed to characterize changes in the prevalence of pandemic-related PTG, and to identify and quantify the relative importance of PTG correlates pre-pandemic, 1- year peri­pandemic, and 2-years post-pandemic onset. A total of 2,441 U.S. military veterans completed Wave 3 assessment of the National Health and Resilience in Veterans Study. In the full sample, a significant decrease from peri­pandemic to 2-years post-pandemic onset was observed in overall pandemic-related PTG (41.5% to 32.2%) and four domains of PTG (appreciation of life, relating to others, personal strength, spiritual changes). Among veterans who screened positive for pandemic-related posttraumatic stress symptoms, the prevalence of pandemic-related PTG was markedly higher and did not change from peri­pandemic to 2-years post-pandemic onset (78.4% to 73.4%). Greater pre-pandemic PTG (personal strength and new possibilities) and greater worries about the effect of pandemic on one's mental health were the strongest correlates of pandemic-related PTG 2-years post-pandemic onset. Results suggest that psychosocial interventions to bolster PTG in relation to early life traumas may help facilitate PTG in response to the pandemic and related crises.