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

Abstract

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.

Impact and Risk of Moral Injury Among Deployed Veterans: Implications for Veterans and Mental Health

“…Similarly, among those taking prescription opioids for pain in the past year, we assessed these patients for opioid use disorder using the Severity of Dependence Scale (SDS), a valid and reliable instatement used past research ( 43 ). We also assessed lifetime marijuana use (never used, some use, moderate use, heavy use), based previous research ( 43 – 45 ). Furthermore, our study included a valid measure of neurotic personality traits used in previous research ( 46 ), as well as a measure of antisocial personality (e.g., as a teenager, ever ran away from home, stole things, fought with parents, teachers, etc.)…”

Genetics and epigenetics of self‐injurious thoughts and behaviors: Systematic review of the suicide literature and methodological considerations

“…An emerging body of work is deploying polygenic scores derived from adult GWAS samples in youth datasets (Daskalakis et al, 2021;Joo et al, 2022;Lee et al, 2021) In addition, aside from psychiatric disorders, a multigenic score built with 750 neurodevelopmental genes explained 4.9% of variance in SA for Europeans (Sokolowski et al, 2016a), while a three-locus score for HTR2A, TPH1 and TPH2 explained 5% of variance in SA for Europeans (Pompili et al, 2017), and a four-locus score across FKBP5, RORA, CHRNA5, and CRHR1 predicted SA or suicide plan in a largely European sample (Boscarino et al, 2022).…”