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.
Keywords: Allostatic load; Childhood adversity; Early-life stress; Mitochondria; mtDNA; mtDNA deletions.
This study examined the number of deletions in mitochondrial DNA, including the number of unique deletions and the cumulative number of deletions, in blood cells of medically healthy young adults with and without early-life stress and further assessed correlations with adult stressors, mental health characteristics, and demographics. We found that early-life stress was associated with greater rates of unique species of mitochondrial DNA deletion breakpoints, and this significant association remained after testing for factors of age, sex, sequencing depth, psychiatric disorders, recent stress, and cell-type proportions.
© 2024 The Authors.