Objectif Exposure to traumatic experiences as well as chronic stress has been shown to increase the risk for a number of psychiatric disorders including major depression and anxiety disorders by inducing longterm alterations in the reactivity of the stress hormone system. These effects can be moderated by genetic variants, one of them being functional polymorphisms in glucocorticoid receptor (GR) co-chaperone gene FKBP5. Preliminary studies in my laboratory suggest that this GxE interaction is mediated by allele-specific de-methylation of intronic glucocorticoid response elements (GREs) within FKBP5. The overarching aim of this grant is to identify the molecular mechanisms by which FKBP5 polymorphisms and early trauma interact to increase the risk for a number of depressive and anxiety disorders. In this application, I propose to extend these preliminary data by experiments in healthy controls and depressed patients, human lymphoblastiod cell lines as well as an animal model in outbred mice showing similar GxE interaction to address the molecular mechanism of these DNA-methylation changes as well as their cellular and system level consequences. Finally we will use expression quantitative trait locus analysis for GR stimulated gene expression to identify new loci relevant for GxE interactions in stress-related disorders.Overall, this proposal will follow up on one of the first putative molecular and systemic mechanisms identified for gene x environment interactions in affective disorders and will establish an animal model mimicking these specific interactions. The findings related to this proposal could be of major importance for understanding the biology of these disorders and to explore novel treatment options, including manipulations of epigenetic modifications. Champ scientifique medical and health sciencesclinical medicinepsychiatryanxiety disorders Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-LS5 - ERC Starting Grant - Neurosciences and neural disorders Appel à propositions ERC-2011-StG_20101109 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Contribution de l’UE € 1 254 119,60 Adresse HOFGARTENSTRASSE 8 80539 Munchen Allemagne Voir sur la carte Région Bayern Oberbayern München, Kreisfreie Stadt Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Allemagne Contribution de l’UE € 1 254 119,60 Adresse HOFGARTENSTRASSE 8 80539 Munchen Voir sur la carte Région Bayern Oberbayern München, Kreisfreie Stadt Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
