title: Epigenetic modification of the glucocorticoid receptor gene is linked to traumatic memory and post-traumatic stress disorder risk in genocide survivors.
abstract: 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.
authors: Department of Psychology, Division of Molecular Neuroscience, University of Basel, CH-4055 Basel, Switzerland, Department Biozentrum, Life Sciences Training Facility, University of Basel, CH-4056 Basel, Switzerland, vanja.vukojevic@unibas.ch dominique.dequervain@unibas.ch.
authors: Vanja
authors: V
authors: Vukojevic
authors: Clinical & Biological Psychology, Institute of Psychology and Education, University of Ulm, D-89069 Ulm, Germany.
authors: Iris-T
authors: IT
authors: Kolassa
authors: Department of Psychology, Division of Molecular Neuroscience, University of Basel, CH-4055 Basel, Switzerland, Department of Psychology, Division of Cognitive Neuroscience, University of Basel, CH-4055 Basel, Switzerland.
authors: Matthias
authors: M
authors: Fastenrath
authors: Department of Psychology, Division of Molecular Neuroscience, University of Basel, CH-4055 Basel, Switzerland, Department of Psychology, Division of Cognitive Neuroscience, University of Basel, CH-4055 Basel, Switzerland.
authors: Leo
authors: L
authors: Gschwind
authors: Department of Psychology, Division of Molecular Neuroscience, University of Basel, CH-4055 Basel, Switzerland, Department of Psychology, Division of Cognitive Neuroscience, University of Basel, CH-4055 Basel, Switzerland.
authors: Klara
authors: K
authors: Spalek
authors: Department of Psychology, Division of Molecular Neuroscience, University of Basel, CH-4055 Basel, Switzerland, Psychiatric University Clinics, University of Basel, CH-4012 Basel, Switzerland.
authors: Annette
authors: A
authors: Milnik
authors: Department of Psychology, Division of Molecular Neuroscience, University of Basel, CH-4055 Basel, Switzerland, Psychiatric University Clinics, University of Basel, CH-4012 Basel, Switzerland, Transfacultary Research Platform, University of Basel, CH-4055 Basel, Switzerland.
authors: Angela
authors: A
authors: Heck
authors: Department of Psychology, Division of Molecular Neuroscience, University of Basel, CH-4055 Basel, Switzerland, Psychiatric University Clinics, University of Basel, CH-4012 Basel, Switzerland, Transfacultary Research Platform, University of Basel, CH-4055 Basel, Switzerland.
authors: Christian
authors: C
authors: Vogler
authors: Clinical & Biological Psychology, Institute of Psychology and Education, University of Ulm, D-89069 Ulm, Germany.
authors: Sarah
authors: http://orcid.org/0000-0002-0887-4672
authors: S
authors: Wilker
authors: Department of Psychology, Division of Molecular Neuroscience, University of Basel, CH-4055 Basel, Switzerland, Department Biozentrum, Life Sciences Training Facility, University of Basel, CH-4056 Basel, Switzerland.
authors: Philippe
authors: P
authors: Demougin
authors: Department of Psychology, Division of Molecular Neuroscience, University of Basel, CH-4055 Basel, Switzerland, Department Biozentrum, Life Sciences Training Facility, University of Basel, CH-4056 Basel, Switzerland.
authors: Fabian
authors: F
authors: Peter
authors: Department of Cognitive Neuroscience and Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, 6525 EZ Nijmegen, Netherlands, and.
authors: Erika
authors: E
authors: Atucha
authors: Department of Psychology, Division of Molecular Neuroscience, University of Basel, CH-4055 Basel, Switzerland, Department Biozentrum, Life Sciences Training Facility, University of Basel, CH-4056 Basel, Switzerland, Psychiatric University Clinics, University of Basel, CH-4012 Basel, Switzerland.
authors: Attila
authors: A
authors: Stetak
authors: Department of Cognitive Neuroscience and Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, 6525 EZ Nijmegen, Netherlands, and.
authors: Benno
authors: B
authors: Roozendaal
authors: Clinical Psychology and Neuropsychology, University of Konstanz, D-78464 Konstanz, Germany.
authors: Thomas
authors: http://orcid.org/0000-0003-1332-4939
authors: T
authors: Elbert
authors: Department of Psychology, Division of Molecular Neuroscience, University of Basel, CH-4055 Basel, Switzerland, Department Biozentrum, Life Sciences Training Facility, University of Basel, CH-4056 Basel, Switzerland, Psychiatric University Clinics, University of Basel, CH-4012 Basel, Switzerland, Transfacultary Research Platform, University of Basel, CH-4055 Basel, Switzerland.
authors: Andreas
authors: A
authors: Papassotiropoulos
authors: Department of Psychology, Division of Cognitive Neuroscience, University of Basel, CH-4055 Basel, Switzerland, Psychiatric University Clinics, University of Basel, CH-4012 Basel, Switzerland, Transfacultary Research Platform, University of Basel, CH-4055 Basel, Switzerland, vanja.vukojevic@unibas.ch dominique.dequervain@unibas.ch.
authors: Dominique J-F
authors: DJ
authors: de Quervain
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000098:blood supply / Q000473:pathology; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D063365:Genocide / Q000523:psychology*; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008568:Memory; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011401:Promoter Regions, Genetic / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012306:Risk; D012432:Rwanda; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics / Q000473:pathology / Q000523:psychology; D017741:Survivors / Q000523:psychology*; D013557:Switzerland; D055815:Young Adult
chemical_list: C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D010100:Oxygen
keywords: DNA methylation; GR; PTSD; memory