This study investigates the combined effects of lifestyle factors (alcohol consumption, diet, physical activity, sleep, smoking, sedentary behavior, and social connection) on depression risk and explores the underlying neurobiological mechanisms. Using data from the UK Biobank (287,282 participants), a multivariate Cox model showed that healthy lifestyles protect against depression. This protective effect was observed across varying genetic risk levels (197,344 participants). Mendelian randomization confirmed a causal link between lifestyle and depression. Brain imaging and peripheral biomarkers (blood and metabolic markers) showed associations with lifestyle. A structural equation model (18,244 participants) revealed a pathway involving lifestyle, brain structure, immunometabolic function, genetics, and depression, suggesting that healthy lifestyles can aid in depression prevention.

Yujie Zhao, Liu Yang, Barbara J. Sahakian, Christelle Langley, Wei Zhang, Kevin Kuo, Zeyu Li, Yihan Gan, Yuzhu Li, Yang Zhao, Jintai Yu, Jianfeng Feng, Wei Cheng