Epigenetic signature of childhood trauma

Childhood abuse is one of the major risk factors for the
development of adult psychopathology though the response to
childhood abuse and other types of early life adversities is not
uniform. Genetic predisposition modulates the exposure to
environmental factors in form of gene by environment interaction.
This has been shown for FKBP5, a modulator of the stress hormone
axis, with certain alleles in FKBP5 conferring a higher risk
towards PTSD in adulthood in response to childhood abuse. This
thesis investigates the potential molecular mechanism behind this
gene by environment interaction and delineates an allele-specific
demethylation mechanism in response to childhood abuse. In
addition, data on genome-wide gene expression and DNA methylation
profiles in peripheral blood in response to childhood abuse is
presented providing evidence for the hypothesis that childhood
trauma leads to a different molecular trajectory towards adult
psychopathology compared to adult traumatization. The data
presented here contribute to our understanding of the molecular
mechanisms underlying gene by environment interactions in
psychiatry and the pathophysiology of trauma- and stress-induced
psychiatric disorders.