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.
Department of Psychiatry, University of California-San Francisco, San Francisco, California.
Biol Psychiatry. 2018 Jul 1;84(1):9-17. doi: 10.1016/j.biopsych.2018.01.012. Epub 2018 Feb 3.
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).
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).
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.
Daily mood and chronic caregiving stress are associated with mitochondrial functional capacity. Mitochondrial health may represent a nexus between psychological stress and health.
慢性生活压力,如照顾压力,可能会促进病理生理学,但潜在的细胞机制尚不清楚。慢性应激可能导致线粒体重新校准,从而导致细胞内线粒体含量或线粒体功能能力(即质量)发生变化。
在这里,我们提出了一种用于人类白细胞的线粒体健康(MHI)的功能指标,该指标可以区分这两种可能性。MHI 整合了核和线粒体 DNA 编码的呼吸链酶活性和线粒体 DNA 拷贝数。然后,我们使用 MHI 来测试以下假设:即日常情绪状态和照顾压力通过比较自闭症谱系障碍儿童的健康母亲(高压力照顾者,n=46)与神经典型儿童的母亲(对照组,n=45),来影响线粒体功能。
MHI 优于单个线粒体功能指标。夜间积极情绪升高与 MHI 较高相关,夜间积极情绪也是照顾与 MHI 之间关联的中介因素。此外,MHI 与采血前几天的积极情绪相关,但与采血后几天的积极情绪不相关,这首次表明在人类中,线粒体可能会在几天内对近期情绪状态做出反应。相应地,照顾者组感知压力较高,积极情绪较低,消极情绪较高,MHI 较低。这种影响不能用核基因组和线粒体基因组之间的不匹配来解释。
每日情绪和慢性照顾压力与线粒体功能能力有关。线粒体健康可能是心理压力与健康之间的联系枢纽。