在早期生活压力的年轻人中,独特的线粒体DNA缺失断点率增加。

IF 4 Q2 NEUROSCIENCES
Teresa E. Daniels , Brooke E. Hjelm , William W. Lewis-de los Angeles , Eric Smith , Audrey A. Omidsalar , Brandi L. Rollins , Anna Sherman , Stephanie Parade , Marquis P. Vawter , Audrey R. Tyrka
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引用次数: 0

摘要

背景:越来越多的证据表明线粒体对社会心理压力有反应。最近的研究表明,线粒体DNA (mtDNA)缺失可能在一些精神疾病中增加,但没有研究检查早期生活压力(ELS)和mtDNA缺失。在这项研究中,我们评估了患有和不患有ELS的医学上健康的年轻人外周血单个核细胞中的mtDNA缺失。方法:参与者(n = 181;(69%为女性),年龄18至40岁,从社区招募。ELS参与者(n = 108)有中度至重度童年虐待;83人还失去了父母,59人有精神障碍。对照组(n = 73)的参与者没有受到虐待、失去父母或精神障碍。标准化访谈和自我报告测量评估了人口变量、压力和心理健康。外周血单个核细胞mtDNA通过远程聚合酶链反应扩增;通过Seq-Well、下一代测序和Splice-Break流水线对mtDNA缺失进行定量。使用线性回归模型评估mtDNA缺失指标与ELS、成人应激源、精神疾病和人口统计学的关系。结果:在校正了年龄、性别和测序深度的影响后,ELS参与者每10000个覆盖范围内的独特mtDNA缺失断点率显著高于未ELS参与者(p < 0.001)。累积mtDNA缺失读取率组间差异不显著。精神疾病和成人应激源与更大的独特mtDNA缺失断点相关(ps < 0.05),但不能解释ELS与mtDNA缺失的关联。结论:ELS参与者中独特mtDNA缺失断点数量的增加表明,线粒体基因组在早期应激背景下发生了可观察到的改变。未来的研究将通过代谢健康措施检查mtDNA缺失。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Increased Rate of Unique Mitochondrial DNA Deletion Breakpoints in Young Adults With Early-Life Stress

Background

Mounting evidence suggests that mitochondria respond to psychosocial stress. Recent studies suggest mitochondrial DNA (mtDNA) deletions may be increased in some psychiatric disorders, but no studies have examined early-life stress (ELS) and mtDNA deletions. In this study, we assessed mtDNA deletions in peripheral blood mononuclear cells of medically healthy young adults with and without ELS.

Methods

Participants (n = 181; 69% female), ages 18 to 40 years, were recruited from the community. Participants with ELS (n = 108) had moderate to severe childhood maltreatment; 83 also had parental loss, and 59 had psychiatric disorders. Participants in the control group (n = 73) had no maltreatment, parental loss, or psychiatric disorders. Standardized interviews and self-report measures assessed demographic variables, stress, and mental health. mtDNA from peripheral blood mononuclear cells was amplified via long-range polymerase chain reaction; mtDNA deletions were quantified via Seq-Well, next-generation sequencing, and the Splice-Break pipeline. Linear regression models were used to assess relationships of mtDNA deletion metrics with ELS, adult stressors, psychiatric disorders, and demographics.

Results

Participants with ELS had significantly greater rates of unique mtDNA deletion breakpoints per 10,000 coverage than participants without ELS (p < .001), correcting for age, sex, and sequencing depth. Cumulative mtDNA deletion read percentage was not significantly different between groups. Psychiatric disorders and adult stressors were associated with greater unique mtDNA deletion breakpoints (ps < .05) but did not account for associations of ELS with mtDNA deletions.

Conclusions

The increased number of unique mtDNA deletion breakpoints in participants with ELS suggests that mitochondrial genomes undergo observable alterations in the context of early stress. Future studies will examine mtDNA deletions with metabolic health measures.
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来源期刊
Biological psychiatry global open science
Biological psychiatry global open science Psychiatry and Mental Health
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