Accelerated aging of the putamen in patients with major depressive disorder

AbstractMajor 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.

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

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.809853 ◽

2022 ◽

Vol 13 ◽

Author(s):

Shixiong Tang ◽

Zhipeng Wu ◽

Hengyi Cao ◽

Xudong Chen ◽

Guowei Wu ◽

...

Keyword(s):

Major Depressive Disorder ◽

Functional Connectivity ◽

Depressive Disorder ◽

Default Mode Network ◽

Regression Models ◽

Accelerated Aging ◽

Major Depressive ◽

Default Mode ◽

Age Related ◽

Main Effect

Major depressive disorder (MDD) is a common psychiatric disorder which is associated with an accelerated biological aging. However, little is known whether such process would be reflected by a more rapid aging of the brain function. In this study, we tested the hypothesis that MDD would be characterized by accelerated aging of the brain’s default-mode network (DMN) functions. Resting-state functional magnetic resonance imaging data of 971 MDD patients and 902 healthy controls (HCs) was analyzed, which was drawn from a publicly accessible, multicenter dataset in China. Strength of functional connectivity (FC) and temporal variability of dynamic functional connectivity (dFC) within the DMN were calculated. Age-related effects on FC/dFC were estimated by linear regression models with age, diagnosis, and diagnosis-by-age interaction as variables of interest, controlling for sex, education, site, and head motion effects. The regression models revealed (1) a significant main effect of age in the predictions of both FC strength and dFC variability; and (2) a significant main effect of diagnosis and a significant diagnosis-by-age interaction in the prediction of FC strength, which was driven by stronger negative correlation between age and FC strength in MDD patients. Our results suggest that (1) both healthy participants and MDD patients experience decrease in DMN FC strength and increase in DMN dFC variability along age; and (2) age-related decrease in DMN FC strength may occur at a faster rate in MDD patients than in HCs. However, further longitudinal studies are still needed to understand the causation between MDD and accelerated aging of brain.

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Major Depressive Disorder and Measures of Cellular Aging: An Integrative Review

Nursing Research and Practice ◽

10.1155/2013/469070 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Patricia Anne Kinser ◽

Debra E. Lyon

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Telomere Length ◽

Accelerated Aging ◽

Telomerase Activity ◽

Cellular Aging ◽

Cumulative Exposure ◽

Nursing Research ◽

Major Depressive ◽

Related Condition

Major depressive disorder (MDD) affects millions of individuals and causes significant suffering worldwide. It has been speculated that MDD is associated with accelerated aging-related biological and functional decline. To examine the accelerated aging hypothesis, one of the biomarkers under study is leukocyte telomeres, and specifically the measure of telomere length and telomerase activity. This review integrates findings from eleven human studies which evaluated telomere length and telomerase activity, in order to synthesize the state of the current science and to inform the development of new knowledge and enhance nursing research of depression using appropriate biobehavioral measures. Although preliminary, the findings from this integrated review suggest that there is evidence to support a conceptualization of depression as a stress-related condition in which telomeres shorten over time in relation to cumulative exposure to the chronic stress of depression. For the purposes of testing in future nursing research, visual representations of the theoretical connection between stress vulnerabilities, depression, and health outcomes and key moderators and mediators involved in this conceptualization are provided. The findings from this review and the conceptual framework provided may be a useful step towards advancing therapeutic nursing interventions for this debilitating chronic condition.

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Major depressive disorder and accelerated aging from a peripheral IGF-1 overexpression perspective

Medical Hypotheses ◽

10.1016/j.mehy.2020.109610 ◽

2020 ◽

Vol 138 ◽

pp. 109610 ◽

Cited By ~ 2

Author(s):

Oleg A. Levada ◽

Alexandra S. Troyan

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Accelerated Aging ◽

Major Depressive

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Major depressive disorder mediates accelerated aging in rats subjected to chronic mild stress

Behavioural Brain Research ◽

10.1016/j.bbr.2017.04.022 ◽

2017 ◽

Vol 329 ◽

pp. 96-103 ◽

Cited By ~ 20

Author(s):

Xiaoxian Xie ◽

Yangyang Chen ◽

Lingyan Ma ◽

Qichen Shen ◽

Liangfeng Huang ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Accelerated Aging ◽

Chronic Mild Stress ◽

Mild Stress ◽

Major Depressive

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“GrimAge,” an epigenetic predictor of mortality, is accelerated in Major Depressive Disorder

10.1101/2020.12.25.20248290 ◽

2020 ◽

Author(s):

Ekaterina Protsenko ◽

Ruoting Yang ◽

Brent Nier ◽

Victor Reus ◽

Rasha Hammamieh ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Smoking Status ◽

Accelerated Aging ◽

Premature Mortality ◽

Cellular Aging ◽

Psychiatric Disease ◽

Healthy Controls ◽

Major Depressive ◽

Age Related

AbstractMajor 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 two 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.

Download Full-text