Trauma’s inherited epigenetic fingerprint observed in children of Holocaust survivors.


The children of traumatized people have long been known to be at increased risk for post-traumatic stress disorder (PTSD). However, there are very few opportunities to examine biologic alterations in the context of a watershed trauma in exposed people and their adult children born after the event.  Therefore, one of the most intensively studied groups in this regard are the children of survivors of the Nazi concentration camps.  Now, a study from researchers at the Icahn School of Medicine at Mount Sinai shows that parental trauma is a relevant contributor to offspring biology.  The team state that this is the first demonstration of an association of preconception parental trauma with epigenetic alterations that is evident in both exposed parent and offspring, providing potential insight into how severe neuropsychiatric trauma can have intergenerational effects.  The opensource study is published in the journal Biological Psychiatry.

Previous studies show that epigenetic processes alter the expression of a gene without producing changes in the DNA sequence. DNA methylation is one of these epigenetic modifications, which regulates genome function through processes that add or remove a methyl group to a specific site in DNA, potentially affecting gene transcription.  Animal studies have demonstrated that epigenetic changes from stress exposure can be passed on to the offspring.  Earlier studies from the lab and others suggest that concentration camp survivors and their children might show changes in the epigenetic regulation of genes. The current study examines these relationships for the first time in humans, with methylation of FKBP5, a stress-related gene that has been associated with PTSD and depression.

The current study analysed blood samples of 32 Holocaust survivors and 22 of their adult children, and Jewish parent-offspring control pairs for methylation of intron 7, a specific region within the FKBP5 gene.  Results show that both Holocaust survivors and their offspring exhibit epigenetic changes at the same site of FKBP5, intron 7, in the opposite direction.  Data findings show that Holocaust survivors had 10% higher methylation than control parents, whereas Holocaust offspring had 7.7% lower methylation than control offspring.

The team state the observation that changes in parent and child are in opposing directions suggests that children of traumatized parents are not simply born with a PTSD-like biology; they may inherit traits that promote resilience as well as vulnerability.  They go on to note that the analysis was not able to disentangle the influence of parental gender and was also unable to identify whether the effects in offspring resulted from trauma effects to the parental gametes or changes occurring to offspring during pregnancy or postnatal.

The team surmise that their findings indicate it may be possible to distinguish changes associated with early adverse experiences in offspring from those associated with trauma in antecedent generations, suggesting the importance for clinicians to inquire about parental trauma in addition to personal trauma.  For the future, the researchers state that their study raises important questions about the intergenerational transmission of traits from traumatized parents to their children, such as a related stress response.

Source: Icahn School of Medicine at Mount Sinai 

 

Inside the cell nucleus, DNA is wrapped around histones (green) and is tightly packaged. In this image, the yellow glow on protruding histone ends represents epigenetic modifications that are associated with silenced genes by tightening the spool of DNA and histones. The green glow denotes modifications that relax the DNA strand, making the DNA accessible to transcription factors and polymerases.  © 2016 Memorial Sloan Kettering Cancer Center.

Inside the cell nucleus, DNA is wrapped around histones (green) and is tightly packaged. In this image, the yellow glow on protruding histone ends represents epigenetic modifications that are associated with silenced genes by tightening the spool of DNA and histones. The green glow denotes modifications that relax the DNA strand, making the DNA accessible to transcription factors and polymerases. © 2016 Memorial Sloan Kettering Cancer Center.

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