Relation of promoter methylation of the structural oxytocin gene to critical life events in major depression: A case control study.
DNA methylation
Epigenetics
Major depression
Oxytocin
Stressful life events
Journal
Journal of affective disorders
ISSN: 1573-2517
Titre abrégé: J Affect Disord
Pays: Netherlands
ID NLM: 7906073
Informations de publication
Date de publication:
01 11 2020
01 11 2020
Historique:
received:
31
01
2020
revised:
02
06
2020
accepted:
05
07
2020
pubmed:
2
8
2020
medline:
16
2
2021
entrez:
2
8
2020
Statut:
ppublish
Résumé
Stressful life events (SLEs) are associated with hyper(re-)activity of the HPA-axis. HPA-axis hyper(re-)activity is thought to be a major risk factor for depression development. SLEs may induce changes in an organism's stress system via epigenetic mechanisms. The neuropeptide oxytocin (OT) is able to attenuate the stress response, and OT pathways are dysregulated in individuals suffering from Major Depressive Disorder (MDD). Therefore, the gene coding for oxytocin (OXT) is a possible target for the investigation of depression development. We collected data on SLEs, OXT promoter methylation (Sequenom Epityper MassArray) and depression severity from 90 MDD inpatients and 90 matched healthy controls. We found MDD inpatients to have a significantly lower OXT methylation than healthy controls. Methylation status was significantly negatively associated with SLEs but only in the group of MDD inpatients. There were no associations between methylation status and depression severity. Methylation in blood samples is only a proxy for epigenetic profiles in brain tissue. We did not assess mRNA or protein levels and cannot draw conclusions regarding the functionality or specificity of differences in OXT methylation between groups. SLEs leave their traces in the epigenetic profiles of the OT system of MDD inpatients. Alterations in epigenetic profiles of the OXT system could constitute a vulnerability factor predisposing individuals for depression development. Better understanding of DNA methylation profiles of depression-associated genes could serve as basis for a personalized medicine, in which pharmacological or psychotherapeutic treatment of depression is tailored to the patient's individual characteristics.
Sections du résumé
BACKGROUND
Stressful life events (SLEs) are associated with hyper(re-)activity of the HPA-axis. HPA-axis hyper(re-)activity is thought to be a major risk factor for depression development. SLEs may induce changes in an organism's stress system via epigenetic mechanisms. The neuropeptide oxytocin (OT) is able to attenuate the stress response, and OT pathways are dysregulated in individuals suffering from Major Depressive Disorder (MDD). Therefore, the gene coding for oxytocin (OXT) is a possible target for the investigation of depression development.
METHODS
We collected data on SLEs, OXT promoter methylation (Sequenom Epityper MassArray) and depression severity from 90 MDD inpatients and 90 matched healthy controls.
RESULTS
We found MDD inpatients to have a significantly lower OXT methylation than healthy controls. Methylation status was significantly negatively associated with SLEs but only in the group of MDD inpatients. There were no associations between methylation status and depression severity.
LIMITATIONS
Methylation in blood samples is only a proxy for epigenetic profiles in brain tissue. We did not assess mRNA or protein levels and cannot draw conclusions regarding the functionality or specificity of differences in OXT methylation between groups.
CONCLUSION
SLEs leave their traces in the epigenetic profiles of the OT system of MDD inpatients. Alterations in epigenetic profiles of the OXT system could constitute a vulnerability factor predisposing individuals for depression development. Better understanding of DNA methylation profiles of depression-associated genes could serve as basis for a personalized medicine, in which pharmacological or psychotherapeutic treatment of depression is tailored to the patient's individual characteristics.
Identifiants
pubmed: 32738668
pii: S0165-0327(20)32513-1
doi: 10.1016/j.jad.2020.07.068
pii:
doi:
Substances chimiques
Oxytocin
50-56-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
829-838Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.