A Mitochondrial Health Index Sensitive to Mood and Caregiving Stress - PubMed (original) (raw)

A Mitochondrial Health Index Sensitive to Mood and Caregiving Stress

Martin Picard et al. Biol Psychiatry. 2018.

Abstract

Background: Chronic life stress, such as the stress of caregiving, can promote pathophysiology, but the underlying cellular mechanisms are not well understood. Chronic stress may induce recalibrations in mitochondria leading to changes either in mitochondrial content per cell, or in mitochondrial functional capacity (i.e., quality).

Methods: Here we present a functional index of mitochondrial health (MHI) for human leukocytes that can distinguish between these two possibilities. The MHI integrates nuclear and mitochondrial DNA-encoded respiratory chain enzymatic activities and mitochondrial DNA copy number. We then use the MHI to test the hypothesis that daily emotional states and caregiving stress influence mitochondrial function by comparing healthy mothers of a child with an autism spectrum disorder (high-stress caregivers, n = 46) with mothers of a neurotypical child (control group, n = 45).

Results: The MHI outperformed individual mitochondrial function measures. Elevated positive mood at night was associated with higher MHI, and nightly positive mood was also a mediator of the association between caregiving and MHI. Moreover, MHI was correlated to positive mood on the days preceding, but not following the blood draw, suggesting for the first time in humans that mitochondria may respond to proximate emotional states within days. Correspondingly, the caregiver group, which had higher perceived stress and lower positive and greater negative daily affect, exhibited lower MHI. This effect was not explained by a mismatch between nuclear and mitochondrial genomes.

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

Keywords: Chronic stress; Daily affect; Mind-body; Mitochondria; Respiratory chain activity; mtDNA copy number.

Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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Conflict of interest statement

DISCLOSURES

The authors report no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1

Figure 1

Mitochondrial health index (MHI) and mitochondrial profiling in human leukocytes. (A) Schematic of a human peripheral blood leukocyte and its mitochondria. The internal components of the mitochondrial respiratory chain (complexes I–V), the tricarboxilic acid ([TCA], also Krebs) cycle, and the mitochondrial genome (mtDNA) are shown in the inset with the inner mitochondrial membrane. (B) Mathematical integration of two nuclear DNA (nDNA)-encoded components (left), and mtDNA-related components (right) into the MHI. (C) Frequency distribution of MHI in the study sample. See Table 3 for statistics. (D) Correlation matrix generated by unsupervised clustering between enzymatic activities, calculated ratios, mtDNA copy number (mtDNAcn), and respiratory chain complexes protein levels. Three major clusters of correlated variables are highlighted. (E) Results from partial least square discriminant analysis model showing rank-ordered variables based on their variable importance in projection (VIP) scores for the first component of the full model; n = 89 to 91 for all. VIP values >1 are considered significant. ATP, adenosine triphosphate; COX, cytochrome c oxidase; CS, citrate synthase; Mito, mitochondrial; SDH, succinate dehydrogenase.

Figure 2

Figure 2

Exploratory analysis showing the strength of the association between daily emotional states and peripheral blood mononuclear cells’ mitochondrial health index (MHI). (A) Combined effect size for the association between MHI and emotional states measured 1) across the week: Week average; 2) over 3 days preceding peripheral blood mononuclear cell collection: Days before; or 3) over 3 days after peripheral blood mononuclear cell collection: Days after. Note that effect sizes are larger for time points preceding blood draw, suggesting a directional relationship from mood to mitochondria. Mood was assessed in the morning and at night as described in the Supplemental Methods and Materials. +p < .10; *p < .05, **p < .01; n = 86 to 89. N.S., not significant. (B) Individual Pearson’s r correlation coefficients between daily measures of positive or negative mood and MHI measured from blood drawn at day 4; n = 86 to 89.

Figure 3

Figure 3

Cross-sectional association between mood and mitochondrial health index (MHI). Average MHI for tertiles of nightly negative and positive mood across the 3 days preceding mitochondrial measurements. Data are mean ± SEM; n = 27 to 29 per tertile.

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