Mitochondrial DNA copy number has been previously shown to be elevated with severe and chronic stress, as well as stress-related pathology like Major Depressive Disorder (MDD) and post-traumatic stress disorder (PTSD). While experimental data point to likely recovery of mtDNA copy number changes after the stressful event, time needed for full recovery and whether it can be achieved are still unknown. Further, while it has been shown that stress-related mtDNA elevation affects multiple tissues, its specific consequences for oogenesis and maternal inheritance of mtDNA has never been explored. In this study, we used qPCR to quantify mtDNA copy number in 15 Holocaust survivors and 102 of their second- and third-generation descendants from the Czech Republic, many of whom suffer from PTSD, and compared them to controls in the respective generations. We found no significant difference in mtDNA copy number in the Holocaust survivors compared to controls, whether they have PTSD or not, and no significant elevation in descendants of female Holocaust survivors as compared to descendants of male survivors or controls. Our results showed no evidence of persistence or inheritance of mtDNA changes in Holocaust survivors, though that does not rule out effects in other tissues or mitigating mechanism for such changes.

Mendel Centre for Plant Genomics and Proteomics CEITEC Masaryk University Brno Czechia National Centre for Biomolecular Research Faculty of Science Masaryk University Brno Czechia

Neuroscience Centre CEITEC Masaryk University Brno Czechia

Neuroscience Centre CEITEC Masaryk University Brno Czechia 1st Neurology Department Hospital St Anne and School of Medicine Masaryk University Brno Czechia

Wellcome Sanger Institute Wellcome Genome Campus Hinxton United Kingdom

Wellcome Sanger Institute Wellcome Genome Campus Hinxton United Kingdom European Bioinformatics Institute Wellcome Genome Campus Hinxton United Kingdom

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