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The role of epigenetic modification of glucocorticoid-related genes in aversive memory and post-traumatic stress disorder

English title The role of epigenetic modification of glucocorticoid-related genes in aversive memory and post-traumatic stress disorder
Applicant De Quervain Dominique
Number 159740
Funding scheme Project funding
Research institution Kognitive Neurowissenschaften Universität Basel
Institution of higher education University of Basel - BS
Main discipline Neurology, Psychiatry
Start/End 01.04.2015 - 31.03.2019
Approved amount 430'008.00
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Keywords (4)

PTSD; Glucocorticoids; Memory; Risk

Lay Summary (German)

Lead
Diese Studie soll uns helfen, die Rolle der Glucocorticoide in der Regulation des Risikos für die posttraumatische Belastungsstörung besser zu verstehen.
Lay summary

Die posttraumatische Belastungsstörung (PTBS) ist durch intensive, schmerzhafte Erinnerungen an ein traumatisches Erlebnis (z.B. Unfall, Vergewaltigung oder Kriegserlebnisse) gekennzeichnet. In früheren Studien konnten wir zeigen, dass Glucocorticoide – körpereigne Stresshormone – eine wichtige regulatorische Rolle in der Stärke der traumatischen Erinnerungen spielen.  Wir konnten ebenfalls zeigen, dass sogenannte epigenetische Veränderungen des Glucocorticoid Rezeptorgens – d.h. Veränderungen, welche die Aktivität dieses Gens regulieren – mit der Stärke der traumatischen Erinnerungen und dem Risiko für PTBS korrelieren. In der aktuellen Studie möchten wir die epigenetischen Untersuchungen auf das gesamte Netzwerk von Glucocorticoid-relevanten Genen ausweiten. Die Befunde dieser Studie werden uns helfen, die Mechanismen eines erhöhten PTBS Risikos nach schlimmen Erlebnissen und die Rolle der Glucocorticoide besser zu verstehen.

Direct link to Lay Summary Last update: 27.03.2015

Responsible applicant and co-applicants

Employees

Name Institute

Publications

Publication
Exome sequencing of healthy phenotypic extremes links TROVE2 to emotional memory and PTSD
Heck Angela, Milnik Annette, Vukojevic Vanja, Petrovska Jana, Egli Tobias, Singer Jochen, Escobar Pablo, Sengstag Thierry, Coynel David, Freytag Virginie, Fastenrath Matthias, Demougin Philippe, Loos Eva, Hartmann Francina, Schicktanz Nathalie, Delarue Bizzini Bernardo, Vogler Christian, Kolassa Iris-Tatjana, Wilker Sarah, Elbert Thomas, Schwede Torsten, Beisel Christian, Beerenwinkel Niko, de Quervain Dominique J.-F., et al. (2017), Exome sequencing of healthy phenotypic extremes links TROVE2 to emotional memory and PTSD, in Nature Human Behaviour, 1(4), 0081-0081.
A peripheral epigenetic signature of immune system genes is linked to neocortical thickness and memory
Freytag Virginie, Carrillo-Roa Tania, Milnik Annette, Sämann Philipp G., Vukojevic Vanja, Coynel David, Demougin Philippe, Egli Tobias, Gschwind Leo, Jessen Frank, Loos Eva, Maier Wolfgang, Riedel-Heller Steffi G., Scherer Martin, Vogler Christian, Wagner Michael, Binder Elisabeth B., de Quervain Dominique J. -F., Papassotiropoulos Andreas (2017), A peripheral epigenetic signature of immune system genes is linked to neocortical thickness and memory, in Nature Communications, 8(1), 15193-15193.

Collaboration

Group / person Country
Types of collaboration
Prof. Andreas Papassotiropoulos/Molekulare Neurowisenschaften, Universität Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. Thomas Elbert/Universität Konstanz Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Iris Kolassa/Universität Ulm Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Communication with the public

Communication Title Media Place Year
Other activities Gründung des stressnetwork.ch German-speaking Switzerland Italian-speaking Switzerland Western Switzerland 2017

Awards

Title Year
Wissenschaftspreis der Stadt Basel für Angela Heck 2018

Associated projects

Number Title Start Funding scheme
191619 Stress 01.06.2020 Agora
147570 Gene-environment interactions in the etiology, symptomatology and treatment of posttraumatic stress disorder 01.07.2013 Project funding

Abstract

Post-traumatic stress disorder (PTSD) is a chronic pathological response to a traumatic event. Aversive memories of such an event are thought to play an important role in the pathogenesis and symptomatology of the disorder. We have previously shown that glucocorticoids play a critical role in regulating aversive memories with potentially important implications for PTSD. Furthermore, we have shown that an epigenetic modification of the glucocorticoid receptor gene promoter is linked to aversive memories and PTSD risk in survivors of the Rwandan genocide. In the current application we propose to extend our previous work by studying epigenetic modifications in genes related to glucocorticoid signalling using gene-set based methods on whole-genome methylation data in survivors of the Rwandan genocide. In addition, we will have the possibility to further explore the findings, in a healthy population with existing genome-wide methylation data regarding aversive memory processing and its underlying neural correlates. The findings of the proposed study will add to the understanding of the mechanisms related to increased PTSD risk after traumatic events.
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