Epigenetics of traumatic stress: The association of NR3C1 methylation and posttraumatic stress disorder symptom changes in response to narrative exposure therapy.


Journal

Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664

Informations de publication

Date de publication:
19 01 2023
Historique:
received: 09 12 2022
accepted: 09 01 2023
revised: 05 01 2023
entrez: 19 1 2023
pubmed: 20 1 2023
medline: 24 1 2023
Statut: epublish

Résumé

Epigenetic processes allow plasticity in gene regulation in response to significant environmental events. Accumulating evidence suggests that effective psychotherapy is accompanied by epigenetic changes, rendering DNA methylation a potential biomarker of therapy success. Due to the central role of glucocorticoid dynamics in stress regulation and the alteration of aversive memories, glucocorticoid receptors are likely involved in the molecular processes that are required to successfully treat Posttraumatic Stress Disorder (PTSD). This study aimed to investigate the relationship between methylation at the glucocorticoid receptor gene (NR3C1) and PTSD treatment success of evidence-based psychotherapy. A sample of N = 153 conflict survivors from Northern Uganda (98 females and 55 males) with PTSD were treated with Narrative Exposure Therapy (NET). Diagnostic interviews and saliva sampling took place at pretreatment and 4 and 10 months after treatment completion. We investigated potential associations between PTSD symptom development and methylation changes at 38 CpG sites spanning NR3C1 over the three times of measurement using the repeated measures correlation. After accounting for multiple comparisons, DNA methylation at CpG site cg25535999 remained negatively associated with PTSD symptoms. These results were followed up by mixed models as well as structural equation modelling. These analyses revealed that treatment responders had a significant cg25535999 methylation increase after treatment with NET. Furthermore, lower methylation at cg25535999 pretreatment predicted a higher symptom improvement. Our results suggest different epigenetic profile dynamics at NR3C1 cg25535999 in therapy responders compared to non-responders and underscore the central role of glucocorticoid signaling in trauma-focused therapy.

Identifiants

pubmed: 36658116
doi: 10.1038/s41398-023-02316-6
pii: 10.1038/s41398-023-02316-6
pmc: PMC9852425
doi:

Substances chimiques

Glucocorticoids 0
Receptors, Glucocorticoid 0
NR3C1 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

14

Informations de copyright

© 2023. The Author(s).

Références

Pharmacol Ther. 2015 May;149:150-90
pubmed: 25550231
Nature. 2013 Aug 22;500(7463):477-81
pubmed: 23925113
J Psychiatr Res. 2016 Dec;83:260-268
pubmed: 27710795
Am J Psychiatry. 2005 Feb;162(2):214-27
pubmed: 15677582
Psychother Res. 2021 Jul;31(6):695-710
pubmed: 33205713
Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6621-5
pubmed: 21444799
Psychoneuroendocrinology. 2015 Jan;51:589-97
pubmed: 25212409
Clin Psychol Rev. 2016 Feb;43:128-41
pubmed: 26574151
Front Psychol. 2015 May 29;6:690
pubmed: 26074844
Psychol Psychother. 2019 Jun;92(2):190-207
pubmed: 30924323
J Neurosci. 2014 Jul 30;34(31):10274-84
pubmed: 25080589
Nat Methods. 2014 Nov;11(11):1138-1140
pubmed: 25262207
Eur J Psychotraumatol. 2020 Sep 15;11(1):1789323
pubmed: 33062203
Neurosci Lett. 2017 May 10;649:156-163
pubmed: 28215878
Curr Genomics. 2018 Dec;19(8):653-664
pubmed: 30532645
Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5585-90
pubmed: 16567641
Transl Psychiatry. 2014 Mar 04;4:e368
pubmed: 24594779
Epigenetics Chromatin. 2019 Dec 5;12(1):71
pubmed: 31805986
Neurosci Biobehav Rev. 2010 Sep;35(1):104-14
pubmed: 20005894
J Trauma Stress. 2020 Apr;33(2):171-180
pubmed: 31951051
Biom J. 2008 Jun;50(3):346-63
pubmed: 18481363
Compr Physiol. 2016 Mar 15;6(2):603-21
pubmed: 27065163
Neurosci Biobehav Rev. 2016 Apr;63:143-57
pubmed: 26872620
Nat Rev Neurosci. 2012 Nov;13(11):769-87
pubmed: 23047775
Genomics. 2011 Oct;98(4):288-95
pubmed: 21839163
Neurosci Biobehav Rev. 2018 Dec;95:85-122
pubmed: 30176278
Clin Psychol Rev. 2010 Dec;30(8):1030-9
pubmed: 20832922
Nat Rev Neurosci. 2017 Jan;18(1):7-19
pubmed: 27881856
BMC Bioinformatics. 2010 Nov 30;11:587
pubmed: 21118553
Psychol Trauma. 2020 Oct;12(7):750-755
pubmed: 32212777
Psychopharmacology (Berl). 2019 Jan;236(1):183-199
pubmed: 30610352
Eur J Psychotraumatol. 2015 Nov 19;6:28306
pubmed: 26589255
Memory. 2018 Mar;26(3):364-376
pubmed: 28625108
J Psychopharmacol. 2021 Jun;35(6):641-651
pubmed: 33908295
J Trauma Stress. 2020 Oct;33(5):688-698
pubmed: 32216170
Depress Anxiety. 2014 May;31(5):429-35
pubmed: 24265104
Front Psychiatry. 2013 Sep 27;4:118
pubmed: 24098286
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 8;89:361-379
pubmed: 30342071
Behav Sci. 1974 Jan;19(1):1-15
pubmed: 4808738
Clin Psychol Rev. 2020 Apr;77:101830
pubmed: 32163803
Transl Psychiatry. 2020 Jul 6;10(1):217
pubmed: 32632143
Eur J Psychotraumatol. 2015 Aug 14;6:28186
pubmed: 26290178
Front Psychol. 2017 Apr 07;8:456
pubmed: 28439244
Bioinformatics. 2007 May 1;23(9):1164-7
pubmed: 17344241
Genome Biol. 2012 Jun 15;13(6):R44
pubmed: 22703947
Biol Psychiatry. 2015 Feb 15;77(4):356-64
pubmed: 24661442
Transl Psychiatry. 2017 Jul 25;7(7):e1181
pubmed: 28742078
JAMA. 2011 Aug 3;306(5):503-12
pubmed: 21813428
Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S186-95
pubmed: 19560279
Depress Anxiety. 2016 Sep;33(9):792-806
pubmed: 27126398

Auteurs

Sarah Wilker (S)

Clinical Psychology and Psychotherapy, Bielefeld University, Universitätsstraße 25, 33615, Bielefeld, Germany. sarah.wilker@uni-bielefeld.de.
vivo international e.V., P.O. box 5108, 78430, Konstanz, Germany. sarah.wilker@uni-bielefeld.de.
Clinical and Biological Psychology, Ulm University, Albert-Einstein-Allee 47, 89081, Ulm, Germany. sarah.wilker@uni-bielefeld.de.

Vanja Vukojevic (V)

Research Platform Molecular and Cognitive Neurosciences (MCN) , Department of Biomedicine, University of Basel, Birmannsgasse 8, 4055, Basel, Switzerland.
Psychiatric University Clinics, University of Basel, CH-4055, Basel, Switzerland.

Anna Schneider (A)

vivo international e.V., P.O. box 5108, 78430, Konstanz, Germany.
Clinical and Biological Psychology, Ulm University, Albert-Einstein-Allee 47, 89081, Ulm, Germany.

Anett Pfeiffer (A)

vivo international e.V., P.O. box 5108, 78430, Konstanz, Germany.

Stefan Inerle (S)

Department of Statistics, TU Dortmund University, Joseph-von-Fraunhofer-Straße 2-4, 44227, Dortmund, Germany.

Markus Pauly (M)

Department of Statistics, TU Dortmund University, Joseph-von-Fraunhofer-Straße 2-4, 44227, Dortmund, Germany.
Research Center Trustworthy Data Science and Security, UA Ruhr, Joseph-von-Fraunhofer-Straße 25, 44227, Dortmund, Germany.

Thomas Elbert (T)

vivo international e.V., P.O. box 5108, 78430, Konstanz, Germany.
Clinical Psychology and Neuropsychology, University of Konstanz, Universitätsstr. 10, 78457, Konstanz, Germany.

Andreas Papassotiropoulos (A)

Research Platform Molecular and Cognitive Neurosciences (MCN) , Department of Biomedicine, University of Basel, Birmannsgasse 8, 4055, Basel, Switzerland.
Psychiatric University Clinics, University of Basel, CH-4055, Basel, Switzerland.

Dominique de Quervain (D)

Research Platform Molecular and Cognitive Neurosciences (MCN) , Department of Biomedicine, University of Basel, Birmannsgasse 8, 4055, Basel, Switzerland.
Psychiatric University Clinics, University of Basel, CH-4055, Basel, Switzerland.

Iris-Tatjana Kolassa (IT)

vivo international e.V., P.O. box 5108, 78430, Konstanz, Germany.
Clinical and Biological Psychology, Ulm University, Albert-Einstein-Allee 47, 89081, Ulm, Germany.

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Classifications MeSH