Increased rate of unique mitochondrial DNA deletion breakpoints in young adults with early life stress

Mounting evidence suggests that mitochondria respond to psychosocial stress. Recent studies suggest mitochondrial DNA (mtDNA) deletions may be increased in some psychiatric disorders, yet no studies have examined early life stress (ELS) and mtDNA deletions. This study assessed mtDNA deletions in peripheral blood mononuclear cells (PBMCs) of medically healthy young adults, with and without ELS. Participants (N=181; 69% female), ages 18-40, were recruited from the community. Participants with ELS (n=108) had moderate-severe childhood maltreatment; n=83 also had parental loss and n=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 demographics, stress, and mental health. MtDNA from PBMCs was amplified via long-range PCR; mtDNA deletions were quantified via Seq-Well, next-generation sequencing and the Splice-Break pipeline. Linear regression models assessed relationships of mtDNA deletion metrics with ELS, adult stressors, psychiatric disorders, and demographics. Participants with ELS had significantly greater rates of unique mtDNA deletion breakpoints per 10k coverage compared to participants without ELS (p