Metabolomic ageing across mental and behavioural disorders

Area of Science:

• Psychiatry
• Metabolomics
• Genetics
• Aging Research

Background:

• Mental disorders are linked to increased morbidity and premature mortality.
• Accelerated biological ageing is a proposed mechanism, but population data across diagnoses is scarce.

Purpose of the Study:

• To investigate metabolomic ageing differences across various mental disorders.
• To explore variations by sex, age group, and genetic liability.

Main Methods:

• Utilized plasma metabolomic data from UK Biobank participants.
• Applied a metabolomic ageing clock (MileAge) to estimate differences between predicted and chronological age.
• Analyzed nine diagnostic groups and 45 disorders, assessing sex, age, and polygenic score associations.

Main Results:

• Substance use, psychotic, affective, and neurotic disorders showed older metabolomic age; psychosis had the largest effect.
• Obsessive-compulsive and eating disorders exhibited younger metabolomic age.
• Associations varied by sex and age, with genetic liability showing mixed effects on metabolomic age.

Conclusions:

• Metabolomic ageing is heterogeneous across mental disorders, with some disorders showing older and others younger biological age.
• Divergence between genetic liability and clinical presentation suggests non-genetic factors shape ageing.
• Sex- and age-specific strategies are crucial for understanding biological ageing in mental health.