"GrimAge," an epigenetic predictor of mortality, is accelerated in major depressive disorder.

Title"GrimAge," an epigenetic predictor of mortality, is accelerated in major depressive disorder.
Publication TypeJournal Article
Year of Publication2021
AuthorsProtsenko, E, Yang, R, Nier, B, Reus, V, Hammamieh, R, Rampersaud, R, W Y Wu, G, Hough, CM, Epel, E, Prather, AA, Jett, M, Gautam, A, Mellon, SH, Wolkowitz, OM
JournalTransl Psychiatry
Volume11
Issue1
Pagination193
Date Published2021 Apr 06
ISSN2158-3188
KeywordsAging, Child, Preschool, Depressive Disorder, Major, DNA Methylation, Epigenesis, Genetic, Epigenomics, Humans
Abstract

Major depressive disorder (MDD) is associated with premature mortality and is an independent risk factor for a broad range of diseases, especially those associated with aging, such as cardiovascular disease, diabetes, and Alzheimer's disease. However, the pathophysiology underlying increased rates of somatic disease in MDD remains unknown. It has been proposed that MDD represents a state of accelerated cellular aging, and several measures of cellular aging have been developed in recent years. Among such metrics, estimators of biological age based on predictable age-related patterns of DNA methylation (DNAm), so-called 'epigenetic clocks', have shown particular promise for their ability to capture accelerated aging in psychiatric disease. The recently developed DNAm metric known as 'GrimAge' is unique in that it was trained on time-to-death data and has outperformed its predecessors in predicting both morbidity and mortality. Yet, GrimAge has not been investigated in MDD. Here we measured GrimAge in 49 somatically healthy unmedicated individuals with MDD and 60 age-matched healthy controls. We found that individuals with MDD exhibited significantly greater GrimAge relative to their chronological age ('AgeAccelGrim') compared to healthy controls (p = 0.001), with a median of 2 years of excess cellular aging. This difference remained significant after controlling for sex, current smoking status, and body-mass index (p = 0.015). These findings are consistent with prior suggestions of accelerated cellular aging in MDD, but are the first to demonstrate this with an epigenetic metric predictive of premature mortality.

DOI10.1038/s41398-021-01302-0
Alternate JournalTransl Psychiatry
PubMed ID33820909
PubMed Central IDPMC8021561
Grant ListR01 HL142051 / HL / NHLBI NIH HHS / United States
TL1 TR001871 / TR / NCATS NIH HHS / United States