| Title: | Metabolomic ageing across mental and behavioural disorders |
| Journal: | BMJ Mental Health |
| Published: | 22 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42331621/ |
| DOI: | https://doi.org/10.1136/bmjment-2025-302181 |
| URL: | https://mentalhealth.bmj.com/content/ebmental/29/1/e302181.full.pdf |
Publication 20571
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Abstract
BACKGROUND: Individuals with mental disorders face excess morbidity and premature mortality. Accelerated ageing has been proposed as a contributing mechanism but population-scale evidence across diverse diagnoses is limited.</p>
OBJECTIVE: To examine whether metabolomic ageing differs across mental disorders and whether associations vary by sex, age group and genetic liability.</p>
METHODS: Using plasma metabolomic profiles from UK Biobank participants, we applied a metabolomic ageing clock (MileAge) to estimate disorder-specific differences between metabolite-predicted and chronological age. Mental disorders were ascertained from health records and self-reported physician diagnoses. We analysed nine diagnostic groups and 45 individual disorders and assessed sex and age group differences and associations with polygenic scores.</p>
FINDINGS: Among 225 212 participants (54% female; mean age 56.97), 38 524 had a diagnosis preceding baseline. Substance use, psychotic, affective and neurotic disorders were associated with a metabolite-predicted age older than chronological age, largest for psychosis (β=0.556, 95% CI 0.250 to 0.861, p<0.001). Obsessive-compulsive and eating disorders were associated with a metabolite-predicted age younger than chronological age. Several associations were stronger in males and in individuals aged <65 years. Higher genetic liability to depression, autism and attention-deficit/hyperactivity disorder predicted an older metabolomic age (β range=0.020 to 0.047), whereas polygenic scores for psychosis and tobacco use disorder predicted a younger metabolomic age (β range=-0.023 to -0.040). For obsessive-compulsive disorder and anorexia nervosa, clinical and genetic associations indicated younger metabolomic ageing.</p>
CONCLUSIONS: Metabolomic ageing in mental disorders is heterogeneous. While many disorders are associated with an older biological age, some are linked to a younger biological age. Divergence between genetic liability and clinical phenotypes suggests that non-genetic factors shape biological ageing differences.</p>
CLINICAL IMPLICATIONS: Biological age should not be assumed to uniformly exceed chronological age across mental disorders. Sex and age-specific approaches could improve understanding of biological ageing processes in psychiatry.</p>
15 Keywords
- Adult
- Age Factors
- Aged
- Aging
- Female
- Genetic Predisposition to Disease
- Genetic Risk Score
- Humans
- Male
- Mental Disorders
- Metabolomics
- Middle Aged
- Sex Factors
- UK Biobank
- United Kingdom
5 Authors
- Julian Mutz
- Lachlan Gilchrist
- Andrea G Allegrini
- Sandra Sanchez Roige
- Cathryn M Lewis
1 Application
| Application ID | Title |
|---|---|
| 45514 | Exploring predictors of healthy ageing in UK Biobank |
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