Pre-conception trauma results in transmission of epigenetic changes from the exposed parents to their children.
An international team lead by Rachel Yehuda, professor at Mount Sinai hospital in New York, and for the molecular analyses Elisabeth Binder, director at the Max Planck Institute of Psychiatry in Munich, studied the genes of 32 Jewish individuals who had been held in concentration camps, experienced torture or had been forced into hiding during the Second World War. The researchers additionally examined the genes of the group’s children who are known to have an increased likelihood of stress disorders, and compared the results with Jewish families living outside Europe during the Holocaust.
The scientists concentrated on epigenetic changes in the FKBP5 gene which has long been the research focus of Elisabeth Binder. “With ‘epigenetic’ we mean all processes that do not change the actual genetic code but alter its accessibility,” explains Elisabeth Binder. “FKPB5 determines how effectively the organism can react to stress hormones, and so regulates the entire stress hormone system. FKBP5 is altered in several diseases such as posttraumatic stress disorder or major depression and has now been associated with intergenerational effects.”
The results suggest that ‘epigenetic inheritance’, where a person’s life experiences can affect the genes of their offspring, may play an important part in a child’s development. “The gene changes in the children did not appear to be mediated by adversity experienced during their own childhood but could only be attributed to Holocaust exposure in the parents,” said Rachel Yehuda. “Environmental influences such as stress, smoking or diet can affect the genes of our children. Early detection of such epigenetic marks may advance the development of preventive strategies to address the intergenerational effects of exposure to trauma.”
Source: Elisabeth Binder – Max Planck Institute
Image Source: The image is in the public domain
Original Research: Abstract for “Holocaust exposure induced intergenerational effects on FKBP5 methylation” by Rachel Yehuda, Nikolaos P. Daskalakis, Linda M. Bierer, Heather N. Bader, Torsten Klengel, Florian Holsboer, and Elisabeth B Binder in Biological Psychiatry. Published online August 23 2015 doi:10.1016/j.biopsych.2015.08.005
Holocaust exposure induced intergenerational effects on FKBP5 methylation
The involvement of epigenetic mechanisms in intergenerational transmission of stress effects has been demonstrated in animals but not in humans.
Cytosine methylation within the gene encoding for FK506-binding-protein-5 (FKBP5) was measured in Holocaust survivors (n=32), their adult offspring (n=22), and respective demographically comparable parent (n=8) – offspring (n=9) controls. Cytosine-phosphate-guanine (CpG) sites for analysis were chosen based on their spatial proximity to the intron 7 glucocorticoid-response-elements (GREs).
Holocaust exposure had an effect on FKBP5 methylation that was observed in exposed parents (F0) as well in their offspring (F1). These effects were observed at bin 3/site 6. Interestingly, in Holocaust survivors, methylation at this site was higher in comparison to controls, whereas in Holocaust offspring, methylation was lower. F0 and F1 methylation levels were significantly correlated. In contrast to the findings at bin 3/site 6, offspring methylation at bin 2/sites 3-5 associated with childhood physical and sexual abuse in interaction with an FKBP5 risk-allele, previously associated with vulnerability to psychological consequences of childhood adversity. The findings suggest the possibility of site-specificity to environmental influences, as sites in bins 3 and 2 were differentially associated with parental trauma and the offspring’s own childhood trauma, respectively. FKBP5 methylation averaged across the three bins examined, associated with wake-up cortisol levels, indicating functional relevance of the methylation measures.
This is the first demonstration of transmission of pre-conception parental trauma to child associated with epigenetic changes in both generations, providing a potential insight into how severe psychological trauma can have intergenerational effects.
“Holocaust exposure induced intergenerational effects on FKBP5 methylation” by Rachel Yehuda, Nikolaos P. Daskalakis, Linda M. Bierer, Heather N. Bader, Torsten Klengel, Florian Holsboer, and Elisabeth B Binder in Biological Psychiatry. Published online August 23 2015 doi:10.1016/j.biopsych.2015.08.005