Genetic and Psychosocial Risk Factors Associated with Suicide Among Community Veterans: Implications for Screening, Treatment and Precision Medicine.

INTRODUCTION: Since veteran suicide is a concern and our knowledge of predictive factors is still limited, our objective was to assess risk factors for suicide, including genetic factors, among deployed veterans. METHODS: For this study, we surveyed 1730 veterans who were outpatients in a multi-hospital system in Pennsylvania. Altogether, 1041 veterans (60%) provided a DNA sample. The genetic risk variants investigated were within loci previously associated with PTSD and substance misuse, including CRHR1, CHRNA5, RORA, and FKBP5 genetic variations, which were used to calculate a polygenic risk score (range=0-8, mean=3.6, SD=1.4). RESULTS: Most veterans (56.2%) were deployed to Vietnam while significant numbers were deployed to Iraq, Afghanistan, and other post-Vietnam conflicts. Overall, 95.1% of the veterans were male, their mean age was 56.2 (SD=12), and 95.6% were Caucasian. Among the veterans, 24% had high combat exposure. The prevalence of lifetime suicidal thoughts was 11.3%. Additionally, 5.7% ever developed a suicide plan or attempted suicide in their lifetimes. Among those with a history of a lifetime suicide attempt or suicide plan, the PTSD genetic risk score was significantly higher (OR=3.96 vs 3.55, p=0.033), but for suicidal thoughts, this association was not significant (p=0.717). In multivariable analysis (MVA) logistic regression, significant predictors of attempting suicide or having a suicide plan were history of depression (OR=5.04, p<0.001), PTSD genetic risk score (OR=1.25, p=0.036), history of childhood abuse/neglect (OR=2.24, p=0.009), and lifetime marijuana use (OR= 1.56, p=0.020). Conversely, rural residence was protective for suicide risk (OR=0.49; p=0.031). For suicidal thoughts, in the MVA genetic risk score was not significant (p=0.697), but history of child abuse/neglect (p<0.001), history of depression (p>0.001), low psychological resilience (p=0.004), and lifetime marijuana use (p=0.022) were significant. DISCUSSION: In this study, we identified genetic risk variants and other predictors for suicide among veterans that may have implications for future screening and clinical care. Further research is advised.

Predicting adolescent alcohol and other drug problems using electronic health records data.

IMPORTANCE: Alcohol and other drug (AOD) use problems may cause significant burden on affected adolescents and their families, yet treatment providers often do not identify these problems early enough. OBJECTIVE: To develop, and internally and externally validate a multivariable prediction model of adolescent AOD problems using child- and maternal-level predictors before age 12, and child-level predictors between ages 12 to 18, as recorded in the electronic health records (EHR). DESIGN: A retrospective cohort study conducted time-to-event analyses using Cox proportional hazards models. SETTING AND PARTICIPANTS: 41,172 children born between 1997 and 2000 at four health plans (Kaiser Permanente Hawaii, KPHI; Kaiser Permanente Northern California, KPNC; Geisinger Clinic, GC; and Henry Ford Health System, HFHS) who had continuous membership since birth and linkable maternal records in the health plan. OUTCOMES: AOD use problems between ages 12 to 18, defined as either: 1) having a contact with the AOD treatment program or 2) receiving a non-tobacco AOD diagnosis in an inpatient or outpatient encounter. EXPOSURES: Candidate predictor variables include demographics, socioeconomic status, and clinical diagnoses of the children and the mothers. RESULTS: Overall, 1400 (3.4%) adolescents had an AOD disorder between ages 12 to 18; the median follow-up time post-age 12 was 5.3 years. The research team developed two final prediction models: a "baseline" model of 10 child-level and 7 maternal-level predictors before age 12, and a more comprehensive "time-varying" model, which incorporated child risk factors after age 12 as time-varying covariates in addition to the baseline model predictors. Model performance evaluation showed good discrimination performance of the models, with the concordance index improved for the time-varying model, especially for prediction of AOD events in late adolescence. CONCLUSIONS AND RELEVANCE: This study identified a number of child and maternal characteristics and diagnoses routinely available in EHR data as predictive of risk for developing AOD problems in adolescence. Further, we found that risk of developing problems varies significantly by the timing and persistence of the risk factors. Findings may have potential clinical implications for prevention and identification of adolescent AOD problems, but more research is needed, especially across additional health systems.

Psychological well-being and alcohol misuse among community-based veterans: results from the Veterans' Health Study.

BACKGROUND: Maladaptive drinking is an increasing concern among military policy makers and healthcare providers. The goal of this study was to assess how social and psychological factors relate to alcohol problems among post-deployed US veterans and how problematic drinking is associated with well-being. METHODS: Data were collected via a telephone survey from a random sample of veterans receiving their healthcare from a large non-VA hospital system in central Pennsylvania (N = 1730). Interviewers inquired about participants' current alcohol consumption, using the CAGE and AUDIT-C scales, and health-related outcomes (general psychological distress, major depression, and self-reported health status). Analyses included demographic, military and nonmilitary stressful events, use of alcohol or drugs to cope post-deployment, use of psychiatric services, and personality characteristics as independent variables. Our sample was 95% male, 96% White, and had a mean age of 59 years old (SD = 12 years). RESULTS: Analyses included demographic, military and nonmilitary stressful events, use of alcohol or drugs to cope post-deployment, use of psychiatric services, and personality characteristics as independent variables. Our sample was 95% male, 96% White, and had a mean age of 59 years old (SD = 12 years). Analyses for our drinking measures show that those who used drugs or alcohol to cope post-deployment were more likely to be problematic drinkers, while positive personality characteristics such as agreeableness and conscientiousness were related to fewer drinking problems. Multivariate logistic regressions for our well-being measures found that alcohol misuse was not related to distress or depression, but that a positive score on the AUDIT-C was associated with a lower likelihood of poor self-rated health. Using alcohol or drugs to cope was related to higher distress. DISCUSSION: We conclude that service providers might consider using post-deployment AUDIT-C and the drugs and alcohol coping questions when screening for possible alcohol and mental health problems among veterans.

Risk and protective factors associated with mental health among female military veterans: results from the veterans' health study.

BACKGROUND: This study focuses on factors that may disproportionately affect female veterans' mental health, compared to men, and is part of a larger study assessing the prevalence of mental health disorders and treatment seeking among formerly deployed US military service members. METHODS: We surveyed a random sample of 1,730 veterans who were patients in a large non-VA hospital system in the US. Based on previous research, women were hypothesized to be at higher risk for psychological problems. We adjusted our results for confounding factors, including history of trauma, childhood abuse, combat exposure, deployments, stressful life events, alcohol misuse, psychological resources, and social support. RESULTS: Among the veterans studied, 5% were female (n = 85), 96% were White (n = 1,161), 22.9% were Iraq/Afghanistan veterans (n = 398), and the mean age was 59 years old (SD = 12). Compared to males, female veterans were younger, unmarried, college graduates, had less combat exposure, but were more likely to have lifetime PTSD (29% vs. 12%.), depression (46% vs. 21%), suicidal ideation (27% vs. 11%), and lifetime mental health service use (67% vs. 47%). Females were also more likely to have low psychological resilience and to have used psychotropic medications in the past year. Using multivariate logistic regression analyses that controlled for risk and protective factors, female veterans had greater risk for lifetime PTSD, depression, suicidal thoughts, and for lifetime use of psychological services, compared to males. Since 95% of the population in this study were male and these results may have been statistically biased, we reran our analyses using propensity score matching. Results were consistent across these analyses. CONCLUSION: Using a sample of post-deployment veterans receiving healthcare services from a large non-VA health system, we find that female veterans are at greater risk for lifetime psychological problems, compared to male veterans. We discuss these findings and their implications for service providers.

Opioid Medication Use Among Chronic Non-Cancer Pain Patients Assessed with a Modified Drug Effects Questionnaire and the Association with Opioid Use Disorder.

PURPOSE: Identifying opioid use disorder (OUD) in patients prescribed opioid therapy for chronic pain is challenging but critically important. Patients may have multiple reasons for taking medications, which they may not reveal if not properly interviewed. In this study, modified Drug Effects Questionnaires (DEQ) were used to assess the liking of and desire to take prescription opioids both for reasons of pain relief and for reasons excluding pain relief. We hypothesized patients would more strongly endorse their medications for reasons of pain relief compared to reasons excluding pain relief, and patients who endorse medications for reasons excluding pain relief may be at higher risk of developing OUD. PATIENTS AND METHODS: A cross-sectional telephone survey was administered to 200 adult outpatients currently being prescribed opioids. A two-year retrospective analysis of electronic health records supplemented survey findings. RESULTS: Based on DSM-5 criteria, 9.0% (n = 18) of patients had moderate or severe OUD. The mean (SD) for drug-liking was 54 (33.4) on a 0 to 100 scale. When liking for pain relief was specified, the mean (SD) was significantly higher compared to when excluding pain relief was specified, 70 (27.8) vs 24 (31.2), p<0.001. A similar pattern was observed for patients' ratings of desire to take their medication again, and "feel good effects" of their medications. Higher scores on items that excluded pain relief were associated with other indications of drug misuse. CONCLUSION: The observed rate of OUD in this patient sample was consistent with findings from other recent research. A better understanding of patients' reasons for using opioid medication may help researchers and health care providers identify those at greatest risk for developing OUD.

Predictors of Current DSM-5 PTSD Diagnosis and Symptom Severity Among Deployed Veterans: Significance of Predisposition, Stress Exposure, and Genetics.

BACKGROUND: Previously we reported a genetic risk score significantly improved PTSD prediction among a trauma-exposed civilian population. In the current study, we sought to assess this prediction among a trauma-exposed military population. METHODS: We examined current PTSD diagnosis and PTSD symptom severity among a random sample of 1042 community-based US military veterans. Main effects and interaction effects were assessed for PTSD genetic risk by trauma exposure using cross-product terms for PTSD x trauma exposures, including combat, lifetime trauma, and adverse childhood exposures. The PTSD risk variants studied were within genetic loci previously associated with PTSD, including CRHR1, CHRNA5, RORA, and FKBP5 genetic variants, which were used to calculate a total PTSD genetic risk score (range=0-8, mean=3.6, SD=1.4). RESULTS: Based on DSM-5 PTSD criteria, 7.1% of veterans (95% CI=5.6-8.8) met criteria for current PTSD. The PTSD genetic risk count was significantly higher among PTSD cases vs non-cases (3.92 vs 3.55, p=0.027). Since the PTSD genetic risk score was not significant in the PTSD diagnosis model, we assessed this association using PTSD symptom severity. Because these symptom data were skewed (mean=9.54, SD=12.71, range=0-76), we used negative binomial regression to assess this outcome. This symptom model included a PTSD genetic risk score, demographic factors, trauma exposures, current insomnia, current depression, concussion history, and attention-deficit disorder, expressed as incident rate ratios (IRR), which is an estimate of one-unit increase in PTSD severity, given other variables are held constant. Variables in the final model included age and sex (both p<0.001), PTSD genetic risk (IRR=1.02, p=0.028), warzone tours (IRR=0.94, p=0.003), childhood abuse (IRR=1.50, p<0.0001), current depression (IRR=1.89, p<0.0001), current insomnia (IRR=2.58, p<0.0001), low social support (IRR=1.19, p<0.0001), attention-deficit disorder (IRR=1.51, p<0.0001), agreeable personality (IRR=0.77, p<0.0001), and concussion (IRR=1.38, p<0.0001). Significant interactions were detected for combat and lifetime trauma exposure by PTSD genetic risk (both p<0.0001), suggesting that the impact of trauma exposures on PTSD severity was lower when the PTSD genetic risk was higher. CONCLUSION: Both warzone and non-warzone factors predicted current PTSD symptoms among veterans, including a PTSD genetic risk score. Interaction effects were detected for combat exposure and lifetime trauma by genetic risk score for PTSD symptoms, suggesting that PTSD symptom manifestation was more dependent on PTSD risk variants than the level of trauma or combat exposure. This suggests that controlling for other factors, the absence of genetic risk variants may confer PTSD resilience. Further research is planned.

Social and Psychological Risk and Protective Factors for Veteran Well-Being: The Role of Veteran Identity and Its Implications for Intervention.

Social psychological theory hypothesizes that one's identity, self-definitions, and meanings used for a particular social role fosters individual purpose in life and affects behavior in specific social situations. As such, it can be protective against the onset of psychological disorders. We examined this hypothesis with data collected from 1,730 military veterans recruited to study the health effects of warzone deployments. The sample was primarily male, older, and White. Our key independent variable was a Likert scale rating the prominence of a respondent's veteran identity: how important it is to the person. Outcome variables included posttraumatic stress disorder (PTSD), suicide ideation, depression, alcohol misuse, and use of VA services. Bivariate analysis suggested that veterans with a prominent veteran identity are older, noncollege graduates, have less income, and had their first deployment to Vietnam. In multivariate analyses, study participants with a prominent veteran identity were less likely to exhibit suicide ideation, but more likely to misuse alcohol and use VA services. We found no differences for PTSD, self-rated health, or depression by veteran identity. Veterans who scored higher on the veteran identity scale appeared to be protected from suicidal thoughts, although they had an elevated risk for alcohol misuse.

Grapheme-Color Synesthesia is Associated with PTSD Among Deployed Veterans: Confirmation of Previous Findings and Need for Additional Research.

Post-traumatic stress disorder (PTSD) is related to alteration in neuropsychological functioning, including visual and other cognitive processes. Grapheme-color synesthesia is a phenomenon in which a letter or number elicits response of a concurrent image or color perception. Since we earlier reported an association between grapheme-color synesthesia and PTSD, our objective in the current study was to validate this association among a new study group and assess risk factors. For this, we surveyed 1,730 military veterans who have been outpatients in the Geisinger Clinic, a multi-hospital system in Pennsylvania, USA. All the study veterans served in a warzone deployment. The association between PTSD and Grapheme-color synesthesia was evaluated. The average age of veterans was 59.6 years among whom 95.1% were male. Current PTSD prevalence rate was observed to be 7.6% (95% C.I. = 6.5-9.0) and in 3.4% of veterans (95% C.I. = 2.7-4.4) grapheme-color synesthesia was found to be positive. Initial bivariate analyses suggested that synesthesia was associated with current PTSD [odds ratio (OR) = 3.3, p<0.001]. Multivariable stepwise logistic regression evaluating the age, sex, education, trauma exposure, current psychological stress, psychotropic medication use, combat exposure, history of concussion, and current depression, confirmed this association (OR = 2.33, p = 0.019). The present study corroborated that Grapheme-color synesthesia was linked to PTSD among a second cohort of deployed military veterans. Further research is recommended in order to validate this observation and to determine whether synesthesia is a risk factor for PTSD.

Evaluation of US Food and Drug Administration-recommended abuse-potential questions in chronic pain patients without history of recreational opioid use: results and plan for research.

BACKGROUND: Existing patient-reported outcome (PRO) assessments that measure the human abuse potential for opioid analgesics have been tested exclusively in experienced recreational opioid users, as required by US Food and Drug Administration (FDA) guidance. METHODS: The goals of the current studies were to modify items from FDA-recommended abuse potential PRO assessments to specify the analgesic benefits versus the euphoric effects of opioids and to ascertain the clarity, understandability, appropriateness, and validity of the modified questions. This was achieved by conducting cognitive debriefing interviews (CDIs) with patients (≥18 and <65 years) who have chronic pain, were prescribed an opioid daily dose of at least 80 morphine-equivalent milligrams (>30 days to ≤180 days from the date of interview), and did not have a history of recreational opioid use. RESULTS: Participants in study 1 (n=30) and study 2 (n=7) had a better understanding of the items designed to measure the concepts of drug liking and items designed to measure the desire to take a drug again when reasons for liking and desire to take again were included in the item wording (namely, "due to pain relief " and "excluding pain relief "). Most participants indicated no interest in taking their medication for reasons other than pain relief. CONCLUSION: Modification of questions in the PRO assessment improved patient understanding of "drug liking" and "desire to take again." Patients with chronic pain who were not recreational opioid users understood the difference between the analgesic and euphoric effects of an opioid drug. The modified questions should assist future researchers in providing a more accurate assessment of the abuse potential of an opioid, as required by regulatory agencies.

Mental Health Impact of Homecoming Experience Among 1730 Formerly Deployed Veterans From the Vietnam War to Current Conflicts: Results From the Veterans' Health Study.

We examined the effects of homecoming support on current mental health among 1730 deployed veterans from Vietnam, Iraq/Afghanistan, Persian Gulf, and other conflicts. The prevalence of current posttraumatic stress disorder (PTSD) was 5.4%, current depression was 8.3%, and 5.4% had suicidal thoughts in the past month. Overall, 26% of veterans had low homecoming support, which was more prevalent among Vietnam veterans (44.3%, p < 0.001). In multivariable logistic regressions, controlling for demographics, combat exposure, number of deployments, trauma history, and operational theater, low postdeployment support was associated with PTSD (odds ratio, 2.13; p = 0.032) and suicidality (odds ratio, 1.91; p < 0.030), but not depression. For suicidality, an interaction was detected for homecoming by theater status, whereby Iraq/Afghanistan veterans with lower homecoming support had a higher probability of suicidal thoughts (p = 0.002). Thus, years after deployment, lower homecoming support was associated with current PTSD and suicidality, regardless of theater and warzone exposures. For suicidality, lower support had a greater impact on Iraq/Afghanistan veterans.