“GrimAge,” an epigenetic predictor of mortality, is accelerated in major depressive disorder

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.

Association of vision loss and depressive symptomatology in older adults assessed for ocular health in senior living facilities

“…A similar situation may hold for depression and visual function, in the sense that depression can cause some changes in visual function (e.g., in contrast sensitivity, 55,56 although we did not observe that in our sample), and may impair visual function in general, in both clinical 21,57 and population 58 samples. Indeed, depression may be associated with a host of negative changes in physical health via accelerated aging effects 59 . In addition to possible effects on objective visual function, depression may also negatively bias self‐reports on a range of variables, including those we measured (e.g., perceived visual function, physical health and social support).…”

Age-Related Decrease in Default-Mode Network Functional Connectivity Is Accelerated in Patients With Major Depressive Disorder

“…Major depressive disorder (MDD), one of the most common serious psychiatric disorders worldwide, is associated with increased risks of many biological and physiological pathologies such as dementia/cognitive decline ( Byers and Yaffe, 2011 ; Holmquist et al, 2020 ), cardiovascular disease ( Gan et al, 2014 ), and osteoporosis ( Cizza et al, 2009 ) which occur in the process of normal aging. Accordingly, there are growing evidences suggesting that MDD leads to an accelerated biological aging as revealed by biochemical ( Wolkowitz et al, 2011 ; Levada and Troyan, 2020 ), genetic ( Simon et al, 2006 ; Protsenko et al, 2021 ), and neuroimaging ( Sacchet et al, 2017 ; Cheng et al, 2020 ; Dunlop et al, 2021 ) characteristics. For instance, it was found that MDD patients are significantly older (with a median gap of 2 years) than their chronological age based on predictable age-related patterns of DNA methylation ( Protsenko et al, 2021 ).…”

“…Accordingly, there are growing evidences suggesting that MDD leads to an accelerated biological aging as revealed by biochemical ( Wolkowitz et al, 2011 ; Levada and Troyan, 2020 ), genetic ( Simon et al, 2006 ; Protsenko et al, 2021 ), and neuroimaging ( Sacchet et al, 2017 ; Cheng et al, 2020 ; Dunlop et al, 2021 ) characteristics. For instance, it was found that MDD patients are significantly older (with a median gap of 2 years) than their chronological age based on predictable age-related patterns of DNA methylation ( Protsenko et al, 2021 ). Structural neuroimaging studies have also reported that age-related reductions in the brain cortical thickness ( Cheng et al, 2020 ) and putamen volumes ( Sacchet et al, 2017 ) are accelerated in MDD.…”

Epigenetic clocks and their association with trajectories in perceived discrimination and depressive symptoms among US middle-aged and older adults

“…Generally, epigenetic age acceleration or faster "epigenetic clock" has been linked to health decline including higher mortality risk [12] and faster cognitive decline [7,9,13,14]. However, few epidemiological studies have directly linked epigenetic clocks or DNAm to MDD [15][16][17] and only two have directly or indirectly examined its association with elevated depressive symptoms [5,6].…”