No Evidence of Persistence or Inheritance of Mitochondrial DNA Copy Number in Holocaust Survivors and Their Descendants

Abstract

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.

Lifelong impact of extreme stress on the human brain: Holocaust survivors study

“…Given the ages of survivors, this data probably reflects the last chance to explore the lifelong impact of this extreme trauma and directly learn from the survivors about their evaluations of a life marked by extreme stress. Data from the genetic part of this study have been partially published, including results about telomere length and mitochondrial DNA ( Cai et al, 2020 ; Konečná et al, 2019 ).…”

Posttraumatic Stress and Posttraumatic Growth in Three Generations of Czech and Slovak Holocaust Survivors

“…The study posited that the heritable signature (i.e., the impact on telomere length and mtDNA copy‐number) would be related to an individual's Holocaust life history and that heritable changes in telomere length or the rate of their shortening and mtDNA in descendants of Holocaust survivors would be able to be identified. The findings from this part of the study demonstrated no significant difference in mtDNA copy number in Holocaust survivors compared to the comparison group (Cai et al., 2020). However, relative telomere length in Holocaust survivors and their offspring was comparable to those found in comparison participants (Konečná et al., 2019).…”

“…The third part of the study focused on brain mapping (i.e., structural MRI scans), with the hypothesis that brain structures related to stress response and resilience would be able to be identified, particularly within the limbic system. The results from the first three parts of the broader study have been partially published (Cai et al., 2020; Konečná et al., 2019) or are being prepared for publication. The fourth part of this broader study focused on the measurement of posttraumatic stress and PTG and is presented herein.…”

Neurobiological and psychological impact of acute war stress on Ukrainian refugees

“…We focused on the neurobiological and psychological impact of war-related stress in Ukrainian women. The study is based on our previous research on the lifelong impact of extreme stress in Holocaust survivors 4,5,6,7,8 . We observed that the Holocaust survivors, 70 to 75 years after the war, experienced a significantly higher frequency of depression symptoms and posttraumatic stress symptoms, and lower levels of well-being as compared to a control group.…”