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

2021 ◽  
Vol 11 (1) ◽  
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 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.

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

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.

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

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.

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

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
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.

scholarly journals Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicolas Salvetat ◽  
Fabrice Chimienti ◽  
Christopher Cayzac ◽  
Benjamin Dubuc ◽  
Francisco Checa-Robles ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rna Editing ◽  
Whole Blood ◽  
Healthy Controls ◽  
Major Depressive ◽  
Suicide Attempters ◽  
Blood Samples ◽  
Depressed Patients ◽  
The Brain

AbstractMental health issues, including major depressive disorder, which can lead to suicidal behavior, are considered by the World Health Organization as a major threat to global health. Alterations in neurotransmitter signaling, e.g., serotonin and glutamate, or inflammatory response have been linked to both MDD and suicide. Phosphodiesterase 8A (PDE8A) gene expression is significantly decreased in the temporal cortex of major depressive disorder (MDD) patients. PDE8A specifically hydrolyzes adenosine 3′,5′-cyclic monophosphate (cAMP), which is a key second messenger involved in inflammation, cognition, and chronic antidepressant treatment. Moreover, alterations of RNA editing in PDE8A mRNA has been described in the brain of depressed suicide decedents. Here, we investigated PDE8A A-to-I RNA editing-related modifications in whole blood of depressed patients and suicide attempters compared to age-matched and sex-matched healthy controls. We report significant alterations of RNA editing of PDE8A in the blood of depressed patients and suicide attempters with major depression, for which the suicide attempt took place during the last month before sample collection. The reported RNA editing modifications in whole blood were similar to the changes observed in the brain of suicide decedents. Furthermore, analysis and combinations of different edited isoforms allowed us to discriminate between suicide attempters and control groups. Altogether, our results identify PDE8A as an immune response-related marker whose RNA editing modifications translate from brain to blood, suggesting that monitoring RNA editing in PDE8A in blood samples could help to evaluate depressive state and suicide risk.

scholarly journals Hot and cold cognitive disturbances in antidepressant-free patients with major depressive disorder: a NeuroPharm study

2020 ◽  
pp. 1-10
Author(s):  
V. H. Dam ◽  
D. S. Stenbæk ◽  
K. Köhler-Forsberg ◽  
C. Ip ◽  
B. Ozenne ◽  
...  
Keyword(s):  
Working Memory ◽  
Major Depressive Disorder ◽  
Reaction Time ◽  
Depressive Disorder ◽  
Healthy Controls ◽  
Cognitive Profiles ◽  
Depression Severity ◽  
Major Depressive ◽  
Depressed Patients ◽  
Cognitive Disturbances

Abstract Background Cognitive disturbances are common and disabling features of major depressive disorder (MDD). Previous studies provide limited insight into the co-occurrence of hot (emotion-dependent) and cold (emotion-independent) cognitive disturbances in MDD. Therefore, we here map both hot and cold cognition in depressed patients compared to healthy individuals. Methods We collected neuropsychological data from 92 antidepressant-free MDD patients and 103 healthy controls. All participants completed a comprehensive neuropsychological test battery assessing hot cognition including emotion processing, affective verbal memory and social cognition as well as cold cognition including verbal and working memory and reaction time. Results The depressed patients showed small to moderate negative affective biases on emotion processing outcomes, moderate increases in ratings of guilt and shame and moderate deficits in verbal and working memory as well as moderately slowed reaction time compared to healthy controls. We observed no correlations between individual cognitive tasks and depression severity in the depressed patients. Lastly, an exploratory cluster analysis suggested the presence of three cognitive profiles in MDD: one characterised predominantly by disturbed hot cognitive functions, one characterised predominantly by disturbed cold cognitive functions and one characterised by global impairment across all cognitive domains. Notably, the three cognitive profiles differed in depression severity. Conclusion We identified a pattern of small to moderate disturbances in both hot and cold cognition in MDD. While none of the individual cognitive outcomes mapped onto depression severity, cognitive profile clusters did. Overall cognition-based stratification tools may be useful in precision medicine approaches to MDD.

scholarly journals Comparison of frontal alpha asymmetry among schizophrenia patients, major depressive disorder patients, and healthy controls

2020 ◽  
Author(s):  
Kuk-In Jang ◽  
Chany Lee ◽  
Sangmin Lee ◽  
Seung Huh ◽  
Jeong-Ho Chae
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Left Hemisphere ◽  
Rating Scales ◽  
Healthy Controls ◽  
Major Depressive ◽  
Alpha Asymmetry ◽  
Alpha Frequency ◽  
Frontal Alpha Asymmetry ◽  
The Difference

Abstract Background: Electroencephalography (EEG) frontal alpha asymmetry (FAA) has been observed in several psychiatric disorders. Dominance in left or right frontal alpha activity remains inconsistent in patients with major depressive disorder (MDD), patients with schizophrenia, and healthy controls. This study compared FAA among patients with MDD and schizophrenia, and healthy controls.Methods: We recruited 20 patients with MDD, 18 patients with schizophrenia, and 16 healthy individuals. The EEG alpha frequency ranged from 8 Hz to 12 Hz. FAA was expressed as the difference between absolute power values of right and left hemisphere electrodes in the alpha frequency range (common-log-transformed frontal right- and left-hemisphere electrodes: F4–F3, F8–F7, FP2–FP1, AF4–AF3, F6–F5, and F2–F1). Hamilton depression and anxiety rating scales were evaluated in patients with MDD. Positive and negative syndrome scales were evaluated in patients with schizophrenia.Results: Patients with schizophrenia showed significantly lower left FAA than healthy controls (F4–F3, schizophrenia vs. healthy controls: -0.10 ± 0.04 vs. -0.05 ± 0.05). There were no significant differences in FAA between patients with schizophrenia and MDD as well as between patients with MDD and healthy controls.Conclusions: The present study suggests that FAA indicates a relatively lower activation of left frontal electrodes in schizophrenia. The left-lateralized FAA could be a neuropathological attribute in patients with schizophrenia, but a lack of sample size and information such as medication and duration of illness might obscure the interpretation and generalization of our findings. Thus, further studies to verify the findings would be warranted.

Hippocampal and Amygdala Changes in Patients With Major Depressive Disorder and Healthy Controls During a 1-Year Follow-Up

2004 ◽  
Vol 65 (4) ◽  
pp. 492-499 ◽  
Author(s):  
Thomas Frodl ◽  
Eva M. Meisenzahl ◽  
Thomas Zetzsche ◽  
Tom Höhne ◽  
Sandra Banac ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Healthy Controls ◽  
Major Depressive
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