Mitochondrial <scp>DNA m.13514G&gt;A</scp> heteroplasmy is associated with depressive symptoms in the elderly

Tranah, Gregory J.; Maglione, Jeanne E.; Yaffe, Kristine; Katzman, Shana M.; Manini, Todd M.; Kritchevsky, Stephen B.; Newman, Anne B.; Harris, Tamara B.; Cummings, Steven R.

doi:10.1002/gps.4928

Cited by 4 publications

(2 citation statements)

References 117 publications

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“…Indeed, in MDD patients, a higher level of mtDNA oxidative damage was observed in leukocytes [ 138 ]. Other mtDNA impairments (e.g., mtDNA deletions and mtDNA mutations) were commonly found in depression [ 139 , 140 , 141 ]. ROS could also induce lipid membrane oxidation that could alter the permeability of both mitochondrial membranes [ 134 , 136 , 142 ].…”

Section: Discussionmentioning

confidence: 99%

Major Depressive Disorder and Oxidative Stress: A Review of Peripheral and Genetic Biomarkers According to Clinical Characteristics and Disease Stages

et al. 2023

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Major depressive disorder (MDD) is currently the main cause of disability worldwide, but its pathophysiology remains largely unknown, especially given its high heterogeneity in terms of clinical phenotypes and biological characteristics. Accordingly, its management is still poor. Increasing evidence suggests that oxidative stress, measured on various matrices such as serum, plasma or erythrocytes, has a critical role in MDD. The aim of this narrative review is to identify serum, plasma and erythrocyte biomarkers of oxidative stress in MDD patients according to disease stage and clinical features. Sixty-three articles referenced on PubMed and Embase between 1 January 1991, and 31 December 2022, were included. Modifications to antioxidant enzymes (mainly glutathione peroxidase and superoxide dismutase) in MDD were highlighted. Non-enzymatic antioxidants (mainly uric acid) were decreased in depressed patients compared to healthy controls. These changes were associated with an increase in reactive oxygen species. Therefore, increased oxidative damage products (principally malondialdehyde, protein carbonyl content and 8-hydroxy-2′-deoxyguanosine) were present in MDD patients. Specific modifications could be identified according to disease stages and clinical features. Interestingly, antidepressant treatment corrected these changes. Accordingly, in patients in remission from depression, oxidative stress markers were globally normalized. This narrative review suggests the particular interest of oxidative stress biomarkers for MDD care that may contribute to the heterogeneity of the disease and provide the opportunity to find new therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Major Depressive Disorder and Oxidative Stress: A Review of Peripheral and Genetic Biomarkers According to Clinical Characteristics and Disease Stages

et al. 2023

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“…Mitochondrial diseases, resulting from mutations in either the mitochondrial or nuclear genomes, affect more than 10 in 100,000 individuals [8]. Psychiatric symptoms frequently correlate with mitochondrial dysfunction [9], as evidenced by a study that found a significant association between heteroplasmy in mtDNA m.13514G>A and depressive symptoms in the elderly [10]. Elevated mtDNA levels have also been associated with heightened anxiety [11].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Interplay between Mitochondrial DNA and Lifestyle Factors in the Pathogenesis of Psychiatric Disorders

Wei,

Cheng,

Zhao

et al. 2024

Depression and Anxiety

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The objectives of this study were to investigate the interaction of mitochondrial DNA (mtDNA) and lifestyle factors in the development of psychiatric disorders and to gain greater insight into their pathogenesis and comorbidity. We analyzed data from approximately 150,000 individuals from the UK Biobank. Mitochondrial gene-by-environment interaction studies (mtGEIS) were performed to assess the relationships between mtDNA and psychiatric disorders, such as anxiety, depression, and self-harm. These disorders were defined using diagnostic and severity indicators derived from the General Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9). Smoking and drinking behaviors were characterized based on UK Biobank criteria. For the mtGEIS, logistic and linear regression models from PLINK 2.0 were employed, accounting for covariates like age, sex, PC1-10, Townsend Deprivation Index (TDI), and educational attainment. We also conducted sex-stratified analyses to detect any gender-specific effects. Our findings highlighted significant associations between mtDNA and three psychiatric disorders. Moreover, the interplay between mtDNA and lifestyle factors showed significant associations with psychiatric disorders (all P values < 0.05). Specifically, two mutant loci, T5004C (BAnx_self=−0.0026, BDep_self=−0.0024, BSelf−harm=−0.0018) and G9123A (BAnx_self=−0.0030, BDep_self=−0.0024, BSelf−harm=−0.0017), were found to reduce the risk of three disorders after interacting with alcohol. Sex-specific differences were also observed. In summary, the expression of mitochondrial genes could be modulated by lifestyle factors like smoking and drinking, potentially affecting psychiatric disorders. These habits might influence mitochondrial respiratory chain activity and the replication and transcriptional regulation of mitochondrial genes, culminating in changes in mitochondrial functionality and subsequently psychiatric disorders.

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Environmental Chemical Exposures and Mitochondrial Dysfunction: a Review of Recent Literature

Reddam

McLarnan

Kupsco

2022

Curr Envir Health Rpt

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Purpose of Review Mitochondria play various roles that are important for cell function and survival; therefore, significant mitochondrial dysfunction may have chronic consequences that extend beyond the cell. Mitochondria are already susceptible to damage, which may be exacerbated by environmental exposures. Therefore, the aim of this review is to summarize the recent literature (2012–2022) looking at the effects of six ubiquitous classes of compounds on mitochondrial dysfunction in human populations. Recent Findings The literature suggests that there are a number of biomarkers that are commonly used to identify mitochondrial dysfunction, each with certain advantages and limitations. Classes of environmental toxicants such as polycyclic aromatic hydrocarbons, air pollutants, heavy metals, endocrine-disrupting compounds, pesticides, and nanomaterials can damage the mitochondria in varied ways, with changes in mtDNA copy number and measures of oxidative damage the most commonly measured in human populations. Other significant biomarkers include changes in mitochondrial membrane potential, calcium levels, and ATP levels. Summary This review identifies the biomarkers that are commonly used to characterize mitochondrial dysfunction but suggests that emerging mitochondrial biomarkers, such as cell-free mitochondria and blood cardiolipin levels, may provide greater insight into the impacts of exposures on mitochondrial function. This review identifies that the mtDNA copy number and measures of oxidative damage are commonly used to characterize mitochondrial dysfunction, but suggests using novel approaches in addition to well-characterized ones to create standardized protocols. We identified a dearth of studies on mitochondrial dysfunction in human populations exposed to metals, endocrine-disrupting chemicals, pesticides, and nanoparticles as a gap in knowledge that needs attention.

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Mitochondrial DNA m.13514G>A heteroplasmy is associated with depressive symptoms in the elderly

Abstract: Increased mtDNA heteroplasmy at m.13514A>G is associated with depressive symptoms in older men. Heteroplasmy may represent a novel biological risk factor for depression.

Cited by 4 publications

References 117 publications

Major Depressive Disorder and Oxidative Stress: A Review of Peripheral and Genetic Biomarkers According to Clinical Characteristics and Disease Stages

Major Depressive Disorder and Oxidative Stress: A Review of Peripheral and Genetic Biomarkers According to Clinical Characteristics and Disease Stages

Exploring the Interplay between Mitochondrial DNA and Lifestyle Factors in the Pathogenesis of Psychiatric Disorders

Environmental Chemical Exposures and Mitochondrial Dysfunction: a Review of Recent Literature

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