ausblenden:
Schlagwörter:
childhood maltreatment, PTSD, DNA methylation, epigenetic
Zusammenfassung:
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.
