Metabolomic ageing across mental and behavioural disorders

Abstract

Background: Individuals with mental and behavioural disorders face increased risk of age-related diseases and premature mortality. Accelerated biological ageing may contribute to this disparity. We investigated differences in metabolomic ageing between individuals with and without mental disorders. Methods: The UK Biobank is a community-based health study of middle-aged and older adults. Mental disorders were identified from hospital inpatient, primary care, death registry and self-reported physician diagnosis data. Plasma metabolites were profiled using the Nightingale Health platform. We examined differences in MileAge delta, the difference between metabolite-predicted and chronological age, across broad ICD-10 diagnostic groups and for 45 individual diagnoses. We further investigated sex-specific associations and tested whether polygenic scores for mental disorders were associated with MileAge delta. Results: Amongst 225,212 participants (54% female; mean age = 56.97 years), 38,524 had at least one mental disorder diagnosis preceding baseline. Substance use, psychotic, affective and neurotic disorders were associated with a metabolite-predicted age exceeding chronological age. In contrast, obsessive-compulsive and eating disorders were associated with a younger MileAge, particularly in females. Associations were generally stronger in males, with several diagnoses showing sex-specific patterns. Higher genetic liability to major depression, autism and ADHD was associated with a MileAge exceeding chronological age, whereas psychosis, tobacco use disorder, obsessive-compulsive disorder and anorexia nervosa polygenic scores were associated with a younger MileAge. Conclusions: Metabolomic ageing varies across mental disorders, with direction and strength of association differing by diagnosis and sex. These findings highlight the heterogeneity of biological ageing across mental disorders and contribute to our understanding of the biological processes linking mental disorders to excess morbidity and premature mortality.