Epigenetics: the long shadow of trauma

Genetic and environmental risk factors as well as their interaction play a role in the development of PTSD. Four single nucelotide polymorphisms (SNPs) of the FKBP5 gene interact with severity of child abuse and predict adult PTSD.

FKBP5 alters glucocorticoid receptor function by decreasing ligand binding and impeding translocationof the receptor complex to the nucleus. Furthermore, FKBP5 is part of an intracellular ultra-short negative feedback loop that regulates glucocorticoid receptor activity. Glucocorticoid receptor activation induces FKBP5transcriptionvia activation at predominantly intronic steroid hormone response elements, leading to increased transcription of FKBP5, entailing restrained glucocorticoid receptor activity. 

Recent work have identified 2 alleles of FKBP5 which differ by a single nucelotide and are either protective ot confer risk of PTSD.

A different site in the FKBP5 gene appears to be involved in the intergenerational transmission of epigenetic changes in holocaust survivors.

For a detailed discussion watch part 3 of our video series on Epigenetics:

https://www.youtube.com/watch?v=wAsypqGSdvU&t=1422s