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Polygenic risk scores for neuropsychiatric, inflammatory, and cardio-metabolic traits highlight possible genetic overlap with suicide attempt and treatment-emergent suicidal ideation.

ABSTRACT: Suicide is the second cause of death among youths. Genetics may contribute to suicidal phenotypes and their co-occurrence in other neuropsychiatric and medical conditions. Our study aimed to investigate the association of polygenic risk scores (PRSs) for 24 neuropsychiatric, inflammatory, and cardio-metabolic traits/diseases with suicide attempt (SA) or treatment-worsening/emergent suicidal ideation (TWESI). PRSs were computed based on summary statistics of genome-wide association studies. Regression analyses were performed between PRSs and SA or TWESI in four clinical cohorts. Results were then meta-analyzed across samples, including a total of 688 patients with SA (N_eff = 2,258) and 214 with TWESI (N_eff = 785). Stratified genetic covariance analyses were performed to investigate functionally cross-phenotype PRS associations. After Bonferroni correction, PRS for major depressive disorder (MDD) was associated with SA (OR = 1.24; 95% CI = 1.11-1.38; p = 1.73 × 10^-4 ). Nominal associations were shown between PRSs for coronary artery disease (CAD) (p = 4.6 × 10^-3 ), loneliness (p = .009), or chronic pain (p = .016) and SA, PRSs for MDD or CAD and TWESI (p = .043 and p = .032, respectively). Genetic covariance between MDD and SA was shown in 86 gene sets related to drugs having antisuicidal effects. A higher genetic liability for MDD may underlie a higher SA risk. Further, but milder, possible modulatory factors are genetic risk for loneliness and CAD.

SUBMITTER: Fanelli G

PROVIDER: S-EPMC9305542 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMedical training poses significant challenge to medical student wellbeing. With the alarming trend of trainee burnout, mental illness, and suicide, previous studies have reported potential risk factors associated with suicidal behaviours among medical students. The objective of this study is to provide a systematic overview of risk factors for suicidal ideation (SI) and suicide attempt (SA) among medical students and summarize the overall risk associated with each risk factor using a meta-analytic approach.MethodsSystemic search of six electronic databases including MEDLINE, Embase, Education Source, Scopus, PsycInfo, and CINAHL was performed from database inception to March 19, 2021. Studies reporting original quantitative or epidemiological data on risk factors associated with SI and SA among undergraduate medical students were included. When two or more studies reported outcome on the same risk factor, a random-effects inverse variance meta-analysis was performed to estimate the overall effect size.ResultsOf 4,053 articles identified, 25 studies were included. Twenty-two studies reported outcomes on SI risk factors only, and three studies on both SI and SA risk factors. Meta-analysis was performed on 25 SI risk factors and 4 SA risk factors. Poor mental health outcomes including depression (OR 6.87; 95% CI [4.80-9.82] for SI; OR 9.34 [4.18-20.90] for SA), burnout (OR 6.29 [2.05-19.30] for SI), comorbid mental illness (OR 5.08 [2.81-9.18] for SI), and stress (OR 3.72 [1.39-9.94] for SI) presented the strongest risk for SI and SA among medical students. Conversely, smoking cigarette (OR 1.92 [0.94-3.92]), family history of mental illness (OR 1.79 [0.86-3.74]) and suicidal behaviour (OR 1.38 [0.80-2.39]) were not significant risk factors for SI, while stress (OR 3.25 [0.59-17.90]), female (OR 3.20 [0.95-10.81]), and alcohol use (OR 1.41 [0.64-3.09]) were not significant risk factors for SA among medical students.ConclusionsMedical students face a number of personal, environmental, and academic challenges that may put them at risk for SI and SA. Additional research on individual risk factors is needed to construct effective suicide prevention programs in medical school.

Project description:ObjectiveThe authors sought to identify predictors of imminent suicide attempt (within 30 days) among U.S. Army soldiers following their first documented suicidal ideation.MethodsUsing administrative data from the Army Study to Assess Risk and Resilience in Servicemembers, the authors identified 11,178 active-duty Regular Army enlisted soldiers (2006-2009) with medically documented suicidal ideation and no prior medically documented suicide attempts. The authors examined risk factors for suicide attempt within 30 days of first suicidal ideation using logistic regression analyses, including sociodemographic and service-related characteristics, psychiatric diagnoses, physical health care visits, injuries, and history of family violence or crime perpetration or victimization.ResultsAmong soldiers with first documented suicidal ideation, 830 (7.4%) attempted suicide, 46.3% of whom (N=387) attempted suicide within 30 days (rate, 35.4 per 1,000 soldiers). Following a series of multivariate analyses, the final model identified females (odds ratio=1.3, 95% CI=1.0, 1.8), combat medics (odds ratio=1.6, 95% CI=1.1, 2.2), individuals with an anxiety disorder diagnosis prior to suicidal ideation (odds ratio=1.3, 95% CI=1.0, 1.6), and those who received a sleep disorder diagnosis on the same day as the recorded suicidal ideation (odds ratio=2.3, 95% CI=1.1, 4.6) as being more likely to attempt suicide within 30 days. Black soldiers (odds ratio=0.6, 95% CI=0.4, 0.9) and those who received an anxiety disorder diagnosis on the same day as suicidal ideation (odds ratio=0.7, 95% CI=0.5, 0.9) were less likely.ConclusionsSuicide attempt risk is highest in the first 30 days following ideation diagnosis and is more likely among women, combat medics, and soldiers with an anxiety disorder diagnosis before suicidal ideation and a same-day sleep disorder diagnosis. Black soldiers and those with a same-day anxiety disorder diagnosis were at decreased risk. These factors may help identify soldiers at imminent risk of suicide attempt.

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Polygenic risk scores for neuropsychiatric, inflammatory, and cardio-metabolic traits highlight possible genetic overlap with suicide attempt and treatment-emergent suicidal ideation.

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