by Wei Hu, Li-Jie Gao, Tian-Shu Liu, Ge Tian, Jia-Ning Wang, Yu-Bin Ma, Zi-Ang Zheng, Tong-Jie Feng, Xiao-Xin Niu, Yi-Ning Yan, Bao-Peng Liu, Cun-Xian Jia Background While physical frailty is linked to psychiatric disorders, its association with suicide attempt (SA) risk is unclear. We aimed to investigate the prospective association of physical frailty with SA risk and the modifying and potential mediating roles of genetic risk and blood biomarkers.
Methods and findings This cohort study included 442,920 UK Biobank participants free of SA at baseline. SA events were extracted by linking hospital inpatient records.
Physical frailty status was assessed using the five-component Fried phenotype and categorized as nonfrail, prefrail, or frail. Genetic risk for SA was estimated through polygenic risk scores and categorized into high, intermediate, and low risk levels.
Cox proportional hazard models were conducted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association. Mendelian randomization (MR) analyses were utilized to examine the association between genetically determined physical frailty and SA.
Mediation analyses were performed to explore potential biological pathways involving circulating biomarkers. During a median follow-up of 13.6 years, 1,518 (0.3%) individuals developed SA.
After multivariable adjustment for sociodemographic characteristics, genetic risk, lifestyle factors, psychiatric disorders, cardiovascular diseases, and cancer, the HRs for SA among those with pre-frailty were 1.61 (95% CI [1.44, 1.80]; P P P = 0.008). Except for low physical activity, all frailty components were significantly associated with an increased risk of SA (all P P = 0.038) to 1.62 (95% CI [1.43, 1.82]; P P P Conclusions Pre-frail and frail states were associated with an increased risk of SA, especially among individuals with high genetic risk.
Incorporating frailty assessment and management into primary prevention strategies may have implications for SA prevention.
PLOS Medicine published a clinical update in Research Highlights on 06 Apr 2026. The item focuses on Physical frailty, genetic risk, mediating biomarkers, and risk of suicide attempt: A prospective cohort study. Open the detail page to review the full original feed content.