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

Clinical Snapshot

Key Findings

• P Value: P < 0.001

• Effect Size: β = 0.261 years acceleration per mental disorder diagnosis

• Primary Outcome: Biological Age Acceleration (BAA) significantly higher in participants with mental and behavioural disorders

• Nnt Or Sensitivity: Strongest associations: developmental disorders (β = 0.717), organic disorders (β = 0.395), substance use disorders (β = 0.338)

• Confidence Interval: 95% CI: 0.229-0.293

Clinical Application

Biological age assessment not routinely available in clinical practice, but findings support comprehensive health monitoring in mental health patients Relevant to Australian mental health services under Medicare Benefits Schedule, supports integrated care approaches recommended by RACGP mental health guidelines and National Mental Health Strategy Adults with mental health conditions across primary care, psychiatry, and general medicine settings

Abstract

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 ageing, with no evidence of horizontal pleiotropy (MR-Egger intercept P > 0.05). Bipolar disorder was associated with slower epigenetic ageing (OR = 0.71 for GrimAge). Alcohol use disorder increased facial ageing (OR = 1.02). Schizophrenia showed no significant associations. CONCLUSIONS: Mental and behavioural disorders are observationally and robustly linked to accelerated biological ageing, with a dose-response by comorbidity. Genetic evidence supports potential causal roles for depression, insomnia, and anxiety in promoting ageing, while bipolar disorder may relate to slower epigenetic ageing. Biological ageing should be considered in the long-term management of mental health.

References

1. 1.Zhu, Z., Cheung, H., Ding, K., Tan, Q., Zhu, Y., Cheng, D., Kong, S., Yin, X., Wang, D., Zhuang, K., Chen, Y., Zhou, J., Luo, Y., Li, Z., & Chen, L. (2026). Biological age acceleration associated with mental and behavioural disorders: Evidence from the UK biobank cohort. Journal of Affective Disorders, 121265. https://doi.org/10.1016/j.jad.2026.121265