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Klengel, Torsten (2016): Epigenetic signature of childhood trauma. Dissertation, LMU München: Faculty of Biology



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.