Psychosocial moderators of polygenic risk for suicidal ideation: Results from a 7-year population-based, prospective cohort study of U.S. veterans.

Polygenic risk scores (PRS) may help inform the etiology of suicidal thoughts and behaviors. In this study, we evaluated whether a suicidality PRS derived from a large genome-wide association study (GWAS) of suicidality from the UK Biobank (N = 122,935) predicted suicidal ideation (SI) in a 7-year population-based, prospective cohort of European-American US veterans (N = 1326). Results revealed that 8.8% (n = 115) of veterans developed new-onset SI, 4.0% (n = 52) had chronic SI, 3.4% (n = 31) had remitted SI, and 83.8% (n = 1128) denied SI over the study period. Suicidality PRSstandardized was positively associated with chronic SI (relative risk ratio [RRR] = 4.54, 95% confidence interval [CI] = 1.01-20.48) and new-onset SI (RRR = 2.97, 95%CI = 1.22-7.23), and negatively associated with remitted SI (RRR = 0.12, 95% CI = 0.02-0.60). Among veterans with higher suicidality PRS, those with higher baseline dispositional optimism had a lower likelihood of chronic SI (RRR = 0.67, 95% CI = 0.49-0.91) and higher likelihood of remitted SI (RRR = 1.98, 95% CI = 1.18-3.31). Among veterans with higher suicidality PRS, those with higher baseline levels of social support were less likely to develop new-onset SI (RRR = 0.95, 95% CI = 0.92-0.99). These interaction effects were enriched for genes implicated in neuron recognition and development, while the PRS main effect was enriched for genes involved in mannosylation. Collectively, results of this study suggest that suicidality PRS is linked prospectively to symptomatic courses of SI, and that dispositional optimism and social support moderate these associations. Interventions targeting these modifiable psychosocial factors may help mitigate risk of SI in veterans with high polygenic risk for suicidality.

Altered gene expression and PTSD symptom dimensions in World Trade Center responders.

Despite experiencing a significant trauma, only a subset of World Trade Center (WTC) rescue and recovery workers developed posttraumatic stress disorder (PTSD). Identification of biomarkers is critical to the development of targeted interventions for treating disaster responders and potentially preventing the development of PTSD in this population. Analysis of gene expression from these individuals can help in identifying biomarkers of PTSD. We established a well-phenotyped sample of 371 WTC responders, recruited from a longitudinal WTC responder cohort using stratified random sampling, by obtaining blood, self-reported and clinical interview data. Using bulk RNA-sequencing from whole blood, we examined the association between gene expression and WTC-related PTSD symptom severity on (i) highest lifetime Clinician-Administered PTSD Scale (CAPS) score, (ii) past-month CAPS score, and (iii) PTSD symptom dimensions using a 5-factor model of re-experiencing, avoidance, emotional numbing, dysphoric arousal and anxious arousal symptoms. We corrected for sex, age, genotype-derived principal components and surrogate variables. Finally, we performed a meta-analysis with existing PTSD studies (total N = 1016), using case/control status as the predictor and correcting for these variables. We identified 66 genes significantly associated with total highest lifetime CAPS score (FDR-corrected p < 0.05), and 31 genes associated with total past-month CAPS score. Our more granular analyses of PTSD symptom dimensions identified additional genes that did not reach statistical significance in our analyses with total CAPS scores. In particular, we identified 82 genes significantly associated with lifetime anxious arousal symptoms. Several genes significantly associated with multiple PTSD symptom dimensions and total lifetime CAPS score (SERPINA1, RPS6KA1, and STAT3) have been previously associated with PTSD. Geneset enrichment of these findings has identified pathways significant in metabolism, immune signaling, other psychiatric disorders, neurological signaling, and cellular structure. Our meta-analysis revealed 10 genes that reached genome-wide significance, all of which were downregulated in cases compared to controls (CIRBP, TMSB10, FCGRT, CLIC1, RPS6KB2, HNRNPUL1, ALDOA, NACA, ZNF429 and COPE). Additionally, cellular deconvolution highlighted an enrichment in CD4 T cells and eosinophils in responders with PTSD compared to controls. The distinction in significant genes between total lifetime CAPS score and the anxious arousal symptom dimension of PTSD highlights a potential biological difference in the mechanism underlying the heterogeneity of the PTSD phenotype. Future studies should be clear about methods used to analyze PTSD status, as phenotypes based on PTSD symptom dimensions may yield different gene sets than combined CAPS score analysis. Potential biomarkers implicated from our meta-analysis may help improve therapeutic target development for PTSD.

Self-rated sleep quality predicts incident suicide ideation in US military veterans: Results from a 7-year, nationally representative, prospective cohort study.

Sleep disturbance is a risk factor for future suicidal behaviours (e.g. suicidal ideation, suicide attempt, death by suicide), and military veterans are at increased risk for both poor sleep and death by suicide relative to civilians. The purpose of this study was to evaluate whether self-reported sleep quality was associated with risk of new-onset suicidal ideation in a 7-year prospective nationally representative cohort study of US military veterans. Multivariable logistic regression analyses were conducted to identify the relation between self-rated sleep quality and incident suicidal ideation in 2,059 veterans without current suicidal ideation or lifetime suicide attempt history at baseline. Relative importance analyses were then conducted to identify the relative variance explained by sleep quality and other significant determinants of incident suicidal ideation. A total of 169 (weighted 8.9%, 95% confidence interval =7.7%-10.3%) veterans developed suicidal ideation over the 7-year study period. Poor self-rated sleep quality was associated with a more than 60% greater likelihood of developing suicidal ideation (relative risk ratio = 1.62, 95% confidence interval = 1.11-2.36), even after adjustment for well-known suicide risk factors such as major depressive disorder. Relative importance analysis revealed that poor self-rated sleep quality accounted for 44.0% of the explained variance in predicting incident suicidal ideation. These results underscore the importance of assessing, monitoring and treating sleep difficulties as part of suicide prevention efforts in military veterans.

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

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

A prospective cohort study of the psychological consequences of the COVID-19 pandemic on frontline healthcare workers in New York City.

OBJECTIVES: We sought to describe the course and correlates of psychological distress in frontline healthcare workers (FHCWs) during the COVID-19 pandemic in New York City (NYC). METHODS: A prospective cohort study of FHCWs at the Mount Sinai Hospital was conducted during the initial 2020 surge (T1) and 7 months later (T2). Psychological distress [i.e., positive screen for pandemic-related post-traumatic stress disorder (PTSD), major depressive disorder (MDD), and/or generalized anxiety disorder (GAD)], occupational and personal exposures to COVID-19, coping strategies, and psychosocial characteristics were assessed. Four courses of psychological distress response were identified: no/minimal, remitted, persistent, and new-onset. Multinomial logistic regression and relative importance analyses were conducted to identify factors associated with courses of distress. RESULTS: Of 786 FHCWs, 126 (16.0%) FHCWs had persistent distress; 150 (19.1%) remitted distress; 35 (4.5%) new-onset distress; and 475 (60.4%) no/minimal distress. Relative to FHCWs with no/minimal distress, those with persistent distress reported greater relationship worries [19.8% relative variance explained (RVE)], pre-pandemic burnout (18.7% RVE), lower dispositional optimism (9.8% RVE), less emotional support (8.6% RVE), and feeling less valued by hospital leadership (8.4% RVE). Relative to FHCWs with remitted symptoms, those with persistent distress reported less emotional support (29.7% RVE), fewer years in practice (28.3% RVE), and psychiatric history (23.6% RVE). CONCLUSIONS: One-fifth of FHCWs in our study experienced psychological distress 7 months following the COVID-19 surge in NYC. Pandemic-related worries, pre-pandemic burnout, emotional support, and feeling valued by leaders were linked to persistent distress. Implications for prevention, treatment, and organizational efforts to mitigate distress in FHCWs are discussed.

Subthreshold post-traumatic stress disorder as a risk factor for post-traumatic stress disorder: results from a sample of USA veterans.

Subthreshold post-traumatic stress disorder (PTSD) is more prevalent than PTSD, yet its role as a potential risk factor for PTSD is unknown. To address this gap, we analysed data from a 7-year, prospective national cohort of USA veterans. Of veterans with subthreshold PTSD at wave 1, 34.3% developed PTSD compared with 7.6% of trauma-exposed veterans without subthreshold PTSD (relative risk ratio 6.4). Among veterans with subthreshold PTSD, specific PTSD symptoms, greater age, cognitive difficulties, lower dispositional optimism and new-onset traumas predicted incident PTSD. Results suggest that preventive interventions targeting subthreshold PTSD and associated factors may help mitigate risk for PTSD in USA veterans.

Successful Aging in Older US Veterans: Results From the 2019-2020 National Health and Resilience in Veterans Study.

OBJECTIVE: To identify the current prevalence, and sociodemographic, military, health, and psychosocial correlates of successful aging in older US veterans. METHODS: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 3,001 US veterans aged greater than or equal to 60 years (mean = 73). Multiple regression and relative importance analyses were conducted to identify key factors associated with successful aging. RESULTS: A total 79% of older veterans rated themselves as aging successfully. Physical and mental health difficulties emerged as the strongest correlates of successful aging (71% variance explained), while psychosocial factors, most notably perceived resilience, purpose in life, and positive expectations about emotional aging, explained 29% of the variance in this outcome. CONCLUSIONS: Nearly 4 of 5 US veterans rate themselves as successful agers. Prevention and treatment efforts designed to mitigate physical and mental health difficulties, and promote protective psychosocial factors may help bolster successful aging in this population.

Psychological Resilience to the Challenges of Physical Aging in Older U.S. Veterans: Results From the 2019-2020 National Health and Resilience in Veterans Study.

OBJECTIVES: To employ a novel analytic approach to quantify psychological resilience to physical health difficulties and identify factors associated with greater resilience in older U.S. veterans. METHODS: Data from a nationally representative sample of older U.S. military veterans (N = 3,001), who participated in the National Health and Resilience in Veterans Study were analyzed to develop the Psychological Resilience Against Physical Difficulties Index (PRAPDI). Multiple regression and relative importance analyses were conducted to identify factors associated with greater PRAPDI scores. RESULTS: Secure attachment style [17.3% relative variance explained (RVE)], mindfulness [16.6% RVE], and purpose in life [15.0% RVE] emerged as the strongest correlates of PRAPDI scores. CONCLUSION: Intervention strategies aimed at fostering mindfulness, attachment security, and purpose in life may help promote psychological resilience to the challenges of physical aging in older veterans.

Moral distress in frontline healthcare workers in the initial epicenter of the COVID-19 pandemic in the United States: Relationship to PTSD symptoms, burnout, and psychosocial functioning.

INTRODUCTION: Little is known about the relationship between moral distress and mental health problems. We examined moral distress in 2579 frontline healthcare workers (FHCWs) caring for coronavirus disease 2019 (COVID-19) patients during the height of the spring 2020 pandemic surge in New York City. The goals of the study were to identify common dimensions of COVID-19 moral distress; and to examine the relationship between moral distress, and positive screen for COVID-19-related posttraumatic stress disorder (PTSD) symptoms, burnout, and work and interpersonal functional difficulties. METHOD: Data were collected in spring 2020, through an anonymous survey delivered to a purposively-selected sample of 6026 FHCWs at Mount Sinai Hospital; 2579 endorsed treating COVID-19 patients and provided complete survey responses. Physicians, house staff, nurses, physician assistants, social workers, chaplains, and clinical dietitians comprised the sample. RESULTS: The majority of the sample (52.7%-87.8%) endorsed moral distress. Factor analyses revealed three dimensions of COVID-19 moral distress: negative impact on family, fear of infecting others, and work-related concerns. All three factors were significantly associated with severity and positive screen for COVID-19-related PTSD symptoms, burnout, and work and interpersonal difficulties. Relative importance analyses revealed that concerns about work competencies and personal relationships were most strongly related to all outcomes. CONCLUSION: Moral distress is prevalent in FHCWs and includes family-, infection-, and work-related concerns. Prevention and treatment efforts to address moral distress during the acute phase of potentially morally injurious events may help mitigate risk for PTSD, burnout, and functional difficulties.

Mental health stigma and barriers to care in World Trade Center responders: Results from a large, population-based health monitoring cohort.

BACKGROUND: Nearly 20 years after the terrorist attacks of September 11, 2001, multiple studies have documented the adverse mental consequences among World Trade Center (WTC) rescue, recovery, and clean-up workers. However, scarce research has examined mental health stigma and barriers to care in WTC-exposed individuals, and no known study has examined whether rates of endorsement may differ between police and "nontraditional" responders, the latter comprising a heterogeneous group of workers and volunteers. OBJECTIVE: To identify the prevalence and correlates of mental health stigma and barriers to care in WTC responders. METHODS: Mental health stigma and barriers to care and their correlates were examined in 6,777 police and 6,272 nontraditional WTC responders. RESULTS: Nontraditional responders endorsed more stigma or barriers to care concerns than police responders. Within a subsample who screened positive for a psychiatric disorder, police were more likely than nontraditional responders to endorse "concerns that negative job consequences might result" (17.9% vs. 9.1%), while nontraditional responders were more likely to endorse "I don't know where to go to find counseling services" (18.4% vs.6.6%). Within this subsample, mental health service need and more severe WTC-related posttraumatic stress disorder symptoms were associated with increased likelihood of endorsing stigma or barriers; pre-9/11 psychiatric history and non-Hispanic Black race/ethnicity were associated with lower likelihood of endorsing stigma or barriers. CONCLUSIONS: Results of this study underscore the burden of mental health stigma and barriers to care in WTC responders, and highlight the need for targeted interventions to address these concerns and promote mental healthcare utilization in this population.

Is there more public support for US Veterans who experience homelessness and posttraumatic stress disorder than other US adults?

This study examined differences in public knowledge and attitudes about homelessness and posttraumatic stress disorder (PTSD) among US Veterans and other adults. A national online survey of 541 US adults from the general population was conducted in November 2016 about knowledge and attitudes about homelessness and PTSD both in reference to the general population and the Veteran population. Results found that participants reported more positive attitudes and endorsed more federal funding for homelessness and PTSD for Veterans than other adults. Participants also reported greater safety concerns about PTSD among Veterans than other adults. Among various background characteristics, only political identification with the Republican party was consistently associated with attitudes in favor of Veterans. The US public reports greater support for addressing homelessness and PTSD among Veterans than other adults, supporting various government and private programs dedicated to Veterans. It is important that publicly supported programs and policies must be evaluated.

Depression and Cognitive Dysfunction in Older U.S. Military Veterans: Moderating Effects of BDNF Val66Met Polymorphism and Physical Exercise.

OBJECTIVE: Depression is associated with increased risk for cognitive dysfunction, yet little is known about genetic and behavioral factors that may moderate this association. Using data from a nationally representative sample of older U.S. military veterans, we examined the direct and interactive effects of depression, brain-derived neurotropic factor (BDNF) Val66Met genotype, and physical exercise on cognitive functioning. METHODS: One thousand three hundred eighty-six older European-American U.S. military veterans (mean age = 63) completed a web-based survey and cognitive assessment. Analyses of covariance were conducted to evaluate the effects of depression, BDNF Met allele carrier status, and physical exercise on these measures. RESULTS: Depressed veterans scored worse than nondepressed veterans on subjective measures of cognitive functioning (Cohen d's = 0.34-0.57) and objective measures of visual learning (d = 0.39) and working memory (d = 0.28). Among depressed veterans, those who were Met allele carriers scored worse than Val/Val homozygotes on subjective cognitive measures (d's = 0.52-0.97) and an objective measure of visual learning (d = 0.36). Engagement in physical exercise moderated the association between depression and cognitive function, with depressed exercisers scoring better than depressed nonexercisers on a subjective measure of reasoning, and objective measures of processing speed, attention, and visual learning (d = 0.58-0.99): further, in depressed Met allele carriers, exercisers scored better than nonexercisers on subjective cognitive (d's = 0.80-1.92), and objective measures of visual learning (d = 0.8-1.31) and working memory (d = 0.67). CONCLUSION: Depression is associated with moderate decrements in cognitive functioning in older U.S. military veterans, and this association is moderated by BDNF Val66Met genotype and physical exercise. Prevention and treatment efforts designed to promote physical exercise may help preserve cognitive functioning in at-risk veterans.

Trauma- and Stress-Induced Craving for Alcohol in Individuals Without PTSD.

AIMS: The main objective of the study was to compare the differences in craving following trauma and stress scripts in individuals with alcohol dependence (AD) who have experienced trauma but did not meet criteria for post-traumatic stress disorder (PTSD). METHODS: Twenty-eight men and women who participated in a treatment trial were included in this study before starting treatment. All had to meet criteria for AD and had experienced trauma at some point of their lives but were never diagnosed with PTSD. All participants had one laboratory session and were exposed to stress, trauma and neutral scripts randomly assigned. Main measures of craving, anxiety and mood were administered before, during and after each script. RESULTS: Stress and trauma scripts induced significantly more craving and anxiety than the neutral scripts. Interestingly, stress scripts produced stronger craving and anxiety than the trauma scripts but only with some measures. Stress and trauma scripts produced significantly more fear, anger and sadness and significantly lower ratings of joy and relaxation than the neutral script. Again, there were no differences between stress and trauma scripts for any of the emotional subscales. CONCLUSIONS: Trauma scripts did not result in stronger craving than stress scripts. These findings suggest that trauma in the absence of PTSD diagnosis does not lead to stronger craving for alcohol.

Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence.

Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling disorder, but there is currently no targeted pharmacological treatment for it. Dysfunction of the glutamate system has been implicated in trauma and stress psychopathology, resulting in a growing interest in modulation of the glutamate system for the treatment of PTSD. Specifically, the metabotropic glutamate receptor 5 (mGluR5) represents a promising treatment target. We used [18F]FPEB, a radioligand that binds to the mGluR5, and positron emission tomography (PET) to quantify in vivo mGluR5 availability in human PTSD vs. healthy control (HCs) subjects. In an independent sample of human postmortem tissue, we investigated expression of proteins that have a functional relationship with mGluR5 and glucocorticoids in PTSD. We observed significantly higher cortical mGluR5 availability in PTSD in vivo and positive correlations between mGluR5 availability and avoidance symptoms. In the postmortem sample, we observed up-regulation of SHANK1, a protein that anchors mGluR5 to the cell surface, as well as decreased expression of FKBP5, implicating aberrant glucocorticoid functioning in PTSD. Results of this study provide insight into molecular mechanisms underlying PTSD and suggest that mGluR5 may be a promising target for mechanism-based treatments aimed at mitigating this disorder.

Mental Healthcare Needs in World Trade Center Responders: Results from a Large, Population-Based Health Monitoring Cohort.

Nearly two decades after the 9/11 attacks on the World Trade Center (WTC), the prevalence of mental disorders remains elevated among traditional (e.g., police) and non-traditional (e.g., construction workers) responders who were involved in the WTC rescue, recovery, and clean-up efforts. To date, however, scarce research has examined factors associated with perceived need for mental health care, which is critical to promoting engagement in mental health treatment in this population. Data were analyzed from 16,170 WTC responders, including 8881 police responders and 7289 non-traditional responders, who completed their first annual health monitoring visit with the WTC Health Program an average of 6.5 years after September 11, 2001. Predisposing, enabling, and need-based factors associated with perceived need for mental health care were examined using multivariable logistic regression analyses. Nearly half (48.7%) of non-traditional responders and a fifth (20.6%) of police responders reported a need for mental health care. The most common perceived needs were for psychotropic medication, individual psychotherapy, and stress management counseling. Predisposing (e.g., female gender) and need-based factors (e.g., WTC-related posttraumatic stress disorder) predicted perceived need for mental health care in both groups. Among non-traditional responders, Hispanic ethnicity and current suicidal ideation were additionally associated with this outcome. Non-traditional WTC responders are substantially more likely than police WTC responders to perceive a need for mental health treatment. Characterization of factors associated with perceived need for treatment can help inform population-based outreach and monitoring efforts designed to promote engagement in mental health treatment in WTC responders.

Beyond stigma: Understanding the "inclined abstainers" in military behavioral health-care utilization.

Low treatment utilization in Soldiers with combat-related Posttraumatic Stress Disorder (PTSD) is an ongoing issue. The critical concern is to better understand factors which prohibit a Soldier with PTSD who wants help from seeking treatment (an "inclined abstainer"). A total of 537 Active Duty Soldiers on a US Army post completed a brief survey comprising psychometrically validated measures of stigma, behavioral health treatment beliefs, resilience, PTSD symptoms, and treatment intentions. Health-care records were prospectively tracked for 12 months to determine the relation between survey answers and treatment utilization. Sixty-three percent of those who acknowledged having a mental health-related problem did not seek help within a one-year period. Greater severity of PTSD symptoms was associated with an increased likelihood of behavioral health engagement. Soldiers that were classified as "inclined abstainers" were also more likely to endorse negative beliefs about psychotherapy and report higher levels of resilience as compared to "inclined actors." These results suggest that a treatment model of PTSD emphasizing self-efficacy and self-reliance, while addressing negative beliefs about psychotherapy, may help promote engagement of behavioral health services among Active Duty Soldiers.

Epigenome-Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans.

BACKGROUND: Hazardous alcohol consumption has significant adverse medical consequences. These effects may be mediated, in part, by alterations in DNA methylation. Thus, DNA methylation signatures in peripheral cells may provide biomarkers of the medical impact of alcohol use and the risk for future alcohol consumption. METHOD: Using a high-density methylation array, we characterized epigenome-wide DNA methylation in saliva cells with respect to alcohol consumption in a large cohort of male European American veterans. In this study, DNA methylation of over 870,000 CpG DNA sites was profiled in 1,135 European American men. Alcohol consumption was assessed using the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C). Linear regression was applied in an epigenome-wide association study (EWAS), adjusted for confounders. Gene set enrichment analysis was performed in the KEGG database with a correction for gene length. RESULTS: We found that a total of 70 CpG sites reached EWAS-corrected significance (p < 6E-08) with small effects on alcohol consumption for individual CpG sites, including 64 new CpG sites and 6 CpG sites that were previously reported as associated with alcohol use disorder, liver function, body mass index, and lipid metabolism. The most significant CpG site was located in SLC7A11 (t = -11.34, p = 2.66E-28), a gene involved specifically in cysteine and glutamate transportation. The 70 significant CpG sites were located on 44 genes, including genes involved in amino acid transport and metabolism systems. We identified 68 pathways with a false discovery rate < 0.05. CONCLUSIONS: We identified novel DNA methylation sites associated with alcohol consumption. Results may shed light on peripheral mechanisms of alcohol consumption on adverse health outcomes among heavy drinkers.

Accelerated DNA Methylation Aging in U.S. Military Veterans: Results From the National Health and Resilience in Veterans Study.

OBJECTIVE: The aim of this study was to identify how a broad range of sociodemographic, military, health, and psychosocial factors relate to accelerated DNA methylation aging (Δage) in a large, contemporary, nationally representative sample of male U.S. veterans. METHODS: Data were analyzed from a sample of U.S. male European-American veterans who participated in the National Health and Resilience in Veterans Study (N = 1,135). RESULTS: Psychosocial factors of lifetime trauma burden, child sexual trauma, and negative beliefs about aging were independently associated with Δage. Three health variables-diabetes, hypertension, and body mass index-emerged as additional correlates of Δage. CONCLUSION: Results of the study build on prior work demonstrating associations between accelerated DNA methylation aging and traumatic stress, highlighting a role for child sexual abuse in particular. They further underscore the importance of targeting negative beliefs about aging, which are modifiable, in prevention efforts designed to forestall accelerated DNA methylation aging.

Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study.

BACKGROUND: Although the ε4 allele of the apolipoprotein E (APOE) gene and posttraumatic stress disorder (PTSD) have been linked to cognitive dysfunction and dementia risk, it is unknown whether they interact to predict cognitive dysfunction. METHODS: We analyzed data from European-American (EA) veterans who participated in the National Health and Resilience in Veterans Study (NHRVS): main sample (n = 1,386) and primary replication sample (n = 509). EAs from the Yale-Penn Study cohort (n = 948) served as a second replication sample. Multivariable analyses were conducted to evaluate the predictive effects of ε4 carrier status and PTSD on cognitive functioning, with a focus on whether PTSD moderates the effect of ε4 carrier status. RESULTS: APOE ε4 allele carrier status (d = 0.15 and 0.17 in the main and primary replication NHRVS samples, respectively) and PTSD (d = 0.31 and 0.17, respectively) were independently associated with lower cognitive functioning. ε4 carriers with PTSD scored lower than those without PTSD (d = 0.68 and 1.29, respectively) with the most pronounced differences in executive function (d's = 0.75-1.50) and attention/concentration (d's = 0.62-1.33). A significant interaction was also observed in the Yale-Penn sample, with ε4 carriers with PTSD making more perseverative errors on a measure of executive function than those without PTSD (24.7% vs. 17.6%; d = 0.59). CONCLUSIONS: APOE ε4 allele carriers with PTSD have substantially greater cognitive difficulties than ε4 carriers without PTSD. These results underscore the importance of assessing, monitoring, and treating PTSD in trauma-affected individuals who are at genetic risk for cognitive decline and dementia.

Public exposure and attitudes about homelessness.

In this study, we conducted a survey among a large sample of U.S. adults to assess attitudes and beliefs about the causes of homelessness, policies to address homelessness, and programs for homeless individuals. In 2016, we surveyed a national sample of 541 adults from 47 different U.S. states using Amazon Mechanical Turk. Of the total sample, 78% reported that homelessness was a problem in their communities and 60% believed homelessness would increase in the next 5 years. The majority expressed compassion for homeless individuals and endorsed structural, intrinsic, and health factors as causes of homelessness. Most participants (73%-88%) believed the federal government should dedicate more funds and policies for homeless individuals. These attitudes were substantially more likely to be reported by participants who were female, lower income, Democrat, and personally exposed to homelessness. Most Americans care about homelessness as a major problem but there are divergent perspectives on solutions to address homelessness based on gender, income level, and political affiliation.