A Mitochondrial Health Index Sensitive to Mood and Caregiving Stress. Author: Picard M1, Prather AA2, Puterman E3, Cuillerier A4, Coccia M2, Aschbacher K5, Burelle Y4, Epel ES2 Affiliation: <sup>1</sup>Department of Psychiatry, Division of Behavioral Medicine, Columbia University Mailman School of Public Health, New York, New York; Department of Neurology, H. Houston Merritt Center, Columbia Translational Neuroscience Initiative, Columbia University Mailman School of Public Health, New York, New York; Columbia Aging Center, Columbia University Mailman School of Public Health, New York, New York. Electronic address: martin.picard@columbia.edu. <sup>2</sup>Department of Psychiatry, University of California-San Francisco, San Francisco, California. <sup>3</sup>School of Kinesiology, Faculty of Education, University of British Columbia, Vancouver, British Columbia. <sup>4</sup>Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada. <sup>5</sup>Department of Medicine, Division of Cardiology, University of California-San Francisco, San Francisco, California. Conference/Journal: Biol Psychiatry. Date published: 2018 Feb 3 Other: Pages: S0006-3223(18)30043-X , Special Notes: doi: 10.1016/j.biopsych.2018.01.012. [Epub ahead of print] , Word Count: 279 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. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. KEYWORDS: Chronic stress; Daily affect; Mind-body; Mitochondria; Respiratory chain activity; mtDNA copy number PMID: 29525040 DOI: 10.1016/j.biopsych.2018.01.012