Background We aimed to assess the lifelong impact of extreme stress on people who survived the Holocaust. We hypothesised that the impact of extreme trauma is detectable even after more than 70 years of an often complicated and stressful post-war life. Methods Psychological testing was performed on 44 Holocaust survivors (HS; median age 81.5 years; 29 women; 26 HS were under the age of 12 years in 1945) and 31 control participants without a personal or family history of the Holocaust (control group (CG); median 80 years; 17 women). Magnetic resonance imaging (MRI) using the 3T Siemens Prisma scanner was performed on 29 HS (median 79 years; 18 women) and 21 CG participants (median 80 years; 11 women). The MRI-tested subgroup that had been younger than 12 years old in 1945 was composed of 20 HS (median 79 years; 17 women) and 21 CG (median 80 years; 11 women). Results HS experienced significantly higher frequency of depression symptoms, posttraumatic stress symptoms, and posttraumatic growth, and lower levels of well-being. The MRI shows a lifelong neurobiological effect of extreme stress. The areas with reduced grey matter correspond to the map of the impact of stress on the brain structure: insula, anterior cingulate, ventromedial cortex including the subgenual cingulate/orbitofrontal cortex, temporal pole, prefrontal cortex, and angular gyrus. HS showed good adjustment to post-war life conditions. Psychological growth may contribute to compensation for the psychological and neurobiological consequences of extreme stress. The reduction of GM was significantly expressed also in the subgroup of participants who survived the Holocaust during their childhood. Conclusion The lifelong psychological and neurobiological changes in people who survived extreme stress were identified more than 70 years after the Holocaust. Extreme stress in childhood and young adulthood has an irreversible lifelong impact on the brain.

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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.