A Mitochondrial Health Index Sensitive to Mood and Caregiving Stress

Picard, Martin; Prather, Aric A.; Puterman, Eli; Cuillerier, Alexanne; Coccia, Michael; Aschbacher, Kirstin; Burelle, Yan; Epel, Elissa S.

doi:10.1016/j.biopsych.2018.01.012

Cited by 97 publications

(135 citation statements)

References 47 publications

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“…Another study targeted caregiver women who care for a child with autism spectrum disorder, which is a psychopathology that fosters elevated levels of psychological distress in the caregivers given its detrimental impact in various life domains of the child (e.g., persistent deficits in social communication, stereotyped or repetitive behaviors and interests). The authors measured respiratory chain maximal enzymatic activities, mitochondrial content, respiratory chain protein abundance, and mtDNAcn in isolated mixed blood cells ( 93 ). Although mitochondrial content was unaltered, mitochondrial respiratory chain activity per mitochondrion–indexed as mitochondrial health–was significantly lower in caregivers compared with controls, with the largest group difference effect size being for COX (which is mtDNA-encoded).…”

Section: Resultsmentioning

confidence: 99%

Psychological Stress and Mitochondria: A Systematic Review

2018

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ObjectiveMitochondria are multifunctional life-sustaining organelles that represent a potential intersection point between psychosocial experiences and biological stress responses. This article provides a systematic review of the effects of psychological stress on mitochondrial structure and function.MethodsA systematic review of the literature investigating the effects of psychological stress on mitochondrial function was conducted. The review focused on experimentally controlled studies allowing us to draw causal inference about the effect of induced psychological stress on mitochondria.ResultsA total of 23 studies met the inclusion criteria. All studies involved male laboratory animals, and most demonstrated that acute and chronic stressors influenced specific facets of mitochondrial function, particularly within the brain. Nineteen studies showed significant adverse effects of psychological stress on mitochondria and four found increases in function or size after stress. In humans, only six observational studies were available, none with experimental designs, and most only measured biological markers that do not directly reflect mitochondrial function, such as mitochondrial DNA copy number.ConclusonsOverall, evidence supports the notion that acute and chronic stressors influence various aspects of mitochondrial biology, and that chronic stress exposure can lead to molecular and functional recalibrations among mitochondria. Limitations of current animal and human studies are discussed. Maladaptive mitochondrial changes that characterize this subcellular state of stress are termed mitochondrial allostatic load. Prospective studies with sensitive measures of specific mitochondrial outcomes will be needed to establish the link between psychosocial stressors, emotional states, the resulting neuroendocrine and immune processes, and mitochondrial energetics relevant to mind-body research in humans.

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Section: Resultsmentioning

confidence: 99%

Psychological Stress and Mitochondria: A Systematic Review

2018

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“…41,42 Isolation of PBMCs requires a larger sample volume and a fractionation step and is not as commonly assessed as whole blood. Previous studies have reported the mtDNA content of PBMCs in disease control groups rather than healthy controls, for example, a range of 200 to 800 mtDNA copies per cell was measured by Picard et al 43 in high-and low-stress caregivers. Casula et al, also reported mtDNA copy numbers within this range in a randomized drug therapy trial with HIV-1 infected patients.…”

Section: T a B L E 3 Circulating Mtdna Content Of Diabetes Patientsmentioning

confidence: 99%

A case for measuring both cellular and cell‐free mitochondrial DNA as a disease biomarker in human blood

et al. 2020

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Circulating mitochondrial DNA (mtDNA), widely studied as a disease biomarker, comprises of mtDNA located within mitochondria, indicative of mitochondrial function, and cell‐free (cf) mtDNA linked to inflammation. The purpose of this study was to determine the ranges of, and relationship between, cellular and cf mtDNA in human blood. Whole blood from 23 controls (HC) and 20 patients with diabetes was separated into peripheral blood mononuclear cells (PBMCs), plasma, and serum. Total DNA was isolated and mtDNA copy numbers were determined using absolute quantification. Cellular mtDNA content in PBMCs was higher than in peripheral blood and a surprisingly high level of cf mtDNA was present in serum and plasma of HC, with no direct relationship between cellular and cf mtDNA content within individuals. Diabetes patients had similar levels of cellular mtDNA compared to healthy participants but a significantly higher cf mtDNA content. Furthermore, only in patients with diabetes, we observed a correlation between whole blood and plasma mtDNA levels, indicating that the relationship between cellular and cf mtDNA content is affected by disease status. In conclusion, when evaluating mtDNA in human blood as a biomarker of mitochondrial dysfunction, it is important to measure both cellular and cf mtDNA.

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“…[102] The robust association between cumulative maternal lifetime stress and reduced placental mtDNAcn in a cohort of pregnant women may provide insight into fetal programming by prenatal stress. [96] Combined measures of mitochondrial function and content may be more informative. To compensate for oxidative damage and deleterious mtDNA mutations following toxic stress exposure, mitochondrial biogenesis increases, and therefore mtDNAcn per cell, may occur as an early adaptive response, but over time, mitochondrial bioenergetic and replicative capacity declines as defective mitochondria accumulate and oxidative stress increases, leading to the mtDNA content depletion.…”

Section: Early Life Stress Affects Mitochondrial Dna Copy Numbermentioning

confidence: 99%

“…Taken together, these results allude to the temporal coordination of mitochondrial biogenesis by the chronic stress response. [96] Novel techniques that measure both mitochondrial oxidative phosphorylation and glycolysis may yield a better understanding of how ELS impacts mitochondrial function, [104] and such measures of mitochondrial function in a longitudinal study would provide insight into the relationship between ELS and mitochondrial dysfunction. [91] The effects of ELS on mtDNAcn warrants further research to cultivate mechanistic understandings of the relationship between mtDNAcn and toxic stress.…”

Section: Early Life Stress Affects Mitochondrial Dna Copy Numbermentioning

confidence: 99%

Adverse Childhood Experiences Run Deep: Toxic Early Life Stress, Telomeres, and Mitochondrial DNA Copy Number, the Biological Markers of Cumulative Stress

2018

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This manuscript reviews recent evidence supporting the utility of telomeres and mitochondrial DNA copy number (mtDNAcn) in detecting the biological impacts of adverse childhood experiences (ACEs) and outlines mechanisms that may mediate the connection between early stress and poor physical and mental health. Critical to interrupting the health sequelae of ACEs such as abuse, neglect, and neighborhood disorder, is the discovery of biomarkers of risk and resilience. The molecular markers of chronic stress exposure, telomere length and mtDNAcn, represent critical biological links between ACEs and poor health outcomes. We examine how telomeres and mtDNAcn may exacerbate health disparities and contribute to the intergenerational transmission of trauma. Finally, we explore how these molecular markers of early stress exposure may help define the role of resilience and develop effective interventions to moderate ACE health risk impact.

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A Mitochondrial Health Index Sensitive to Mood and Caregiving Stress

Abstract: Daily mood and chronic caregiving stress are associated with mitochondrial functional capacity. Mitochondrial health may represent a nexus between psychological stress and health.

Cited by 97 publications

References 47 publications

Psychological Stress and Mitochondria: A Systematic Review

Psychological Stress and Mitochondria: A Systematic Review

A case for measuring both cellular and cell‐free mitochondrial DNA as a disease biomarker in human blood

Adverse Childhood Experiences Run Deep: Toxic Early Life Stress, Telomeres, and Mitochondrial DNA Copy Number, the Biological Markers of Cumulative Stress

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