Genotype-specific effects of physical activities on self-harm behavior in depressed patients: findings from the UK Biobank

Background Physical activities are widely implemented for non-pharmacological intervention in depression. However, there is little evidence supporting their genotype-specific effectiveness in reducing the risk of intentional self-harm in midlife and late-life depression patients. Aims To assess whether the specific type and amount of physical activity is associated with the risk of intentional self-harm behavior among patients with depression phenotype. Method We developed the bidirectional analytic model to investigate the genotype-specific effectiveness (BAIGE) on UK Biobank. After the genetic stratification on the depression phenotype cohort using hierarchical clustering, multivariable logistic regression models and Cox proportional hazard models were built to investigate the associations between physical activity and the risk of intentional self-harm behavior. Results A total of 28,923 subjects with depression phenotype were included in the study. In retrospective cohort analysis, the moderate and highly active groups were at lower risk of hospitalizations (moderate: adjusted odds ratio [OR], 0.77 [95% CI, 0.61-0.98], high: OR, 0.76 [95% CI, 0.60-0.97]). In the follow-up prospective cohort analysis, light-intensity physical activity (LIPA) was associated with a lower risk of hospitalizations in one genetic cluster (adjusted hazard ratio [HR], 0.26 [95% CI, 0.08 – 0.88]), which was distinguished by three genetic variants: rs1432639, rs4543289, and rs11209948. Compliance with the guideline-level moderate-to-vigorous physical activities was not significantly related to the risk of hospitalizations. Conclusions Physical activities, particularly a certain amount of light-intensity physical activity, mitigate the risk of hospitalizations due to self-harm in depression patients with a specific genotype.