Mental and behavioural disorders are observationally and robustly linked to accelerated biological ageing, with a dose-response by comorbidity, and genetic evidence supports potential causal roles for depression, insomnia, and anxiety in promoting ageing.
Key Findings
Results
Ever having a diagnosis of a mental and behavioural disorder was associated with higher Biological Age Acceleration (BAA).
β = 0.261, 95% CI: 0.229–0.293, P < 0.001
502,411 UK Biobank participants were included, of whom 78,674 had ICD-10 Mental and Behavioural Disorders
Propensity score matching (1:1) was used to control for confounding
Robustness checks were conducted using heteroscedasticity-robust and cluster-robust standard errors
Results
Disorders of psychological development showed the strongest association with Biological Age Acceleration among disorder subtypes.
β = 0.717 for disorders of psychological development
β = 0.395 for organic mental and behavioural disorders
β = 0.338 for mental and behavioural disorders due to psychoactive substance use
These were the three strongest associations observed across ICD-10 disorder categories
Results
Biological Age Acceleration increased with increasing comorbidity count in a dose-response relationship.
P-trend < 0.001 across comorbidity count categories
This dose-response pattern was observed in the observational analysis of the UK Biobank cohort
Results
Mendelian randomisation analysis indicated potential causal effects of depression, insomnia, and anxiety on accelerated biological ageing as measured by the frailty index.
Depression: OR = 5.12 for frailty index
Insomnia: OR = 2.04 for frailty index
Anxiety: OR = 1.06 for frailty index
No evidence of horizontal pleiotropy was found (MR-Egger intercept P > 0.05)
Strong genetic instruments were used (F > 10), validated through sensitivity analyses including MR-Egger, Cochran's Q, and leave-one-out tests
Results
Bipolar disorder was associated with slower epigenetic ageing in the Mendelian randomisation analysis.
OR = 0.71 for GrimAge epigenetic clock
This inverse association was in contrast to the accelerated ageing observed for depression, insomnia, and anxiety
Two-sample MR design was used to assess this causal relationship
Results
Alcohol use disorder was causally associated with increased facial ageing in the Mendelian randomisation analysis.
OR = 1.02 for facial ageing biomarker
This finding was from two-sample MR assessing the causal effect of genetic liability to alcohol use disorder on ageing biomarkers
Results
Schizophrenia showed no significant associations with biological ageing biomarkers in the Mendelian randomisation analysis.
Six mental and behavioural disorders were assessed in the MR analysis: depression, insomnia, anxiety, bipolar disorder, alcohol use disorder, and schizophrenia
Four ageing biomarkers were examined, including the frailty index, GrimAge, and facial ageing
Schizophrenia was the only disorder among the six examined that showed no significant MR associations
Methods
The study used a two-stage analytical approach combining observational propensity-score-matched analysis with two-sample Mendelian randomisation.
Observational stage: 502,411 UK Biobank participants with 78,674 carrying ICD-10 Mental and Behavioural Disorder diagnoses, propensity score matched 1:1
MR stage: two-sample MR assessed causal effects of genetic liability to six mental and behavioural disorders on four ageing biomarkers
BAA was defined as biological age minus chronological age
Sensitivity analyses included MR-Egger, Cochran's Q, and leave-one-out tests
Zhu Z, Cheung H, Ding K, Tan Q, Zhu Y, Cheng D, et al.. (2026). Biological age acceleration associated with mental and behavioural disorders: Evidence from the UK biobank cohort.. Journal of affective disorders. https://doi.org/10.1016/j.jad.2026.121265