Objective:

To examine whether metabolomic ageing differs across mental disorders and whether associations vary by sex, age group and genetic liability.

Approach:

• Study Design: Utilized plasma metabolomic profiles from UK Biobank participants and applied a metabolomic ageing clock (MileAge) to estimate disorder-specific differences between metabolite-predicted and chronological age.
• Participants: Included 225,212 participants, with 38,524 having a diagnosis preceding baseline.
• Analysis: Assessed nine diagnostic groups and 45 individual disorders, focusing on sex and age group differences and associations with polygenic scores.

Key Findings:

• Substance use, psychotic, affective, and neurotic disorders were associated with a metabolite-predicted age older than chronological age, particularly for psychosis (β=0.556, 95% CI 0.250 to 0.861, p<0.001).
• Obsessive-compulsive and eating disorders were linked to a younger metabolomic age (β range=−0.023 to −0.040).
• Associations were generally stronger in males and individuals aged <65 years.
• Higher genetic liability to depression, autism, and ADHD predicted an older metabolomic age (β range=0.020 to 0.047), while polygenic scores for psychosis and tobacco use disorder predicted a younger metabolomic age.

Interpretation:

Metabolomic ageing in mental disorders is heterogeneous, with some disorders linked to older biological age and others to younger biological age. Non-genetic factors may influence biological ageing differences.

Limitations:

• The study may not encompass all mental disorders and their complexities.
• Findings may not be generalizable beyond the UK Biobank population.

Conclusion:

Biological age should not be assumed to uniformly exceed chronological age across mental disorders, and sex and age-specific approaches could enhance understanding of biological ageing processes in psychiatry.