Epigenetic modification of the glucocorticoid receptor gene is linked to traumatic memory and post-traumatic stress disorder risk in genocide survivors
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Recent evidence suggests that altered expression and epigenetic modification of the glucocorticoid receptor gene (NR3C1) are related to the risk of post-traumatic stress disorder (PTSD). The underlying mechanisms, however, remain unknown. Because glucocorticoid receptor signaling is known to regulate emotional memory processes, particularly in men, epigenetic modifications of NR3C1 might affect the strength of traumatic memories. Here, we found that increased DNA methylation at the NGFI-A (nerve growth factor-induced protein A) binding site of the NR3C1 promoter was associated with less intrusive memory of the traumatic event and reduced PTSD risk in male, but not female survivors of the Rwandan genocide. NR3C1 methylation was not significantly related to hyperarousal or avoidance symptoms. We further investigated the relationship between NR3C1 methylation and memory functions in a neuroimaging study in healthy subjects. Increased NR3C1 methylation–which was associated with lower NR3C1 expression–was related to reduced picture recognition in male, but not female subjects. Furthermore, we found methylation-dependent differences in recognition memory-related brain activity in men. Together, these findings indicate that an epigenetic modification of the glucocorticoid receptor gene promoter is linked to interindividual and gender-specific differences in memory functions and PTSD risk.
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VUKOJEVIC, Vanja, Iris-Tatjana KOLASSA, Matthias FASTENRATH, Leo GSCHWIND, Klara SPALEK, Annette MILNIK, Angela HECK, Christian VOGLER, Sarah WILKER, Philippe DEMOUGIN, Fabian PETER, Erika ATUCHA, Attila STETAK, Benno ROOZENDAAL, Thomas ELBERT, Andreas PAPASSOTIROPOULOS, Dominique J.-F. DE QUERVAIN, 2014. Epigenetic modification of the glucocorticoid receptor gene is linked to traumatic memory and post-traumatic stress disorder risk in genocide survivors. In: The Journal of Neuroscience. 2014, 34(31), pp. 10274-10284. ISSN 0270-6474. eISSN 1529-2401. Available under: doi: 10.1523/JNEUROSCI.1526-14.2014BibTex
@article{Vukojevic2014Epige-30035, year={2014}, doi={10.1523/JNEUROSCI.1526-14.2014}, title={Epigenetic modification of the glucocorticoid receptor gene is linked to traumatic memory and post-traumatic stress disorder risk in genocide survivors}, url={http://www.jneurosci.org/content/34/31/10274.short}, number={31}, volume={34}, issn={0270-6474}, journal={The Journal of Neuroscience}, pages={10274--10284}, author={Vukojevic, Vanja and Kolassa, Iris-Tatjana and Fastenrath, Matthias and Gschwind, Leo and Spalek, Klara and Milnik, Annette and Heck, Angela and Vogler, Christian and Wilker, Sarah and Demougin, Philippe and Peter, Fabian and Atucha, Erika and Stetak, Attila and Roozendaal, Benno and Elbert, Thomas and Papassotiropoulos, Andreas and de Quervain, Dominique J.-F.} }
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