Accelerated Epigenetic Ageing in Major Depressive Disorder

摘要: Background: Major depressive disorder (MDD) is a severe, heritable psychiatric associated with shortened lifespan and comorbidities of advancing age. It unknown however whether MDD accelerated biological ageing relative to chronological This hypothesis was tested using the epigenetic clock as measure Methods: To address main hypothesis, peripheral blood, we derived measures Epigenetic Age Acceleration (EAA) in 3,833 controls 1,219 cases based on Hannum Horvath clocks Generation Scotland (GS:SFHS, mean age 48 years, std dev 14.5). Models controlled for relatedness, sex, cell counts, processing batch (basic model), well additional covariates smoking drinking status, body mass index (BMI) (full models). Results: Accelerated found versus (β=0.0804, p=0.012 equivalent 0.20 years) both basic full models. Significant MDD*age interactions indicated greatest effects at younger ranges. No significant differences were observed clock. BMI only covariate attenuate relationship between EAAHorvath MDD. Further, genetic correlation analysis overlap aetiology (rG=0.20, p=0.03), (rG=0.10, p=9.86x10-6), but not (rG=0.14, p=0.125). Mediation partial mediation depression status through (β=0.0028; p=0.0248, ~13%). Conclusion: These data imply that partially mediated BMI.