Biological age acceleration associated with mental and behavioural disorders: Evidence from the UK biobank cohort.

作者：Zixi Zhu, Hoiyin Cheung, Ke Ding, Qilian Tan, Yifei Zhu, Dan Cheng, Siyu Kong, Xuan Yin, Danpeng Wang, Kewei Zhuang, Yuling Chen, Jifang Zhou, Yan Luo, Zezhi Li, Lihai Chen · 发表于：Journal of Affective Disorders · 年份：2026 · DOI：10.1016/j.jad.2026.121265 · 研究领域：Medicine

BACKGROUND Mental and behavioural disorders may accelerate biological ageing, but comprehensive evidence integrating observational and causal approaches is lacking. METHODS We performed observational and Mendelian randomisation (MR) analyses. First, 502,411 UK Biobank participants (78,674 with ICD-10 Mental and Behavioural Disorders) were propensity score matched (1:1). Biological Age Acceleration (BAA = biological age - chronological age) was regressed on mental and behavioural disorder status, and robustness checks were conducted using heteroscedasticity-robust and cluster-robust standard errors. Second, two-sample MR assessed causal effects of genetic liability to six mental and behavioural disorders on four ageing biomarkers, using strong genetic instruments (F > 10) and validated through sensitivity analyses including MR-Egger, Cochran's Q, and leave-one-out tests. RESULTS Ever having a diagnosis of a mental and behavioural disorder was associated with higher BAA (β = 0.261, 95% CI: 0.229-0.293, P < 0.001). Strongest associations were observed for disorders of psychological development (β = 0.717), organic mental and behavioural disorders (β = 0.395), and mental and behavioural disorders due to psychoactive substance use (β = 0.338). BAA increased with comorbidity count (P-trend <0.001). MR indicated potential causal effects of depression (OR = 5.12 for frailty index), insomnia (OR = 2.04 for frailty index), and anxiety (OR = 1.06 for frailty index) on accelerated ag...