Epigenome-wide DNA methylation in unipolar depression - predictive biomarker of antidepressant treatment response?

Abstract: Background
Despite the well-documented efficacy of antidepressant agents for the treatment of major depressive disorder (MDD), initial treatment nonresponse rates are high. Recent years have seen an increase in research into predictive biomarkers toward improving diagnosis and individualized treatment. Among those, epigenetic mechanisms such as DNA methylation constitute promising candidate markers in predicting antidepressant treatment response in MDD. The present study sought to address epigenome-wide DNA methylation as a predictor of antidepressant treatment response in the largest sample to date of patients with MDD.

Methods
Epigenome-wide DNA methylation was analyzed using the Infinium MethylationEPIC BeadChip in peripheral blood of n = 230 Caucasian patients with MDD receiving 6-week antidepressant treatment in a naturalistic in-patient setting as well as in a subsample of n = 107 patients primarily receiving continuous treatment with serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors. Treatment response was assessed by means of the Hamilton Depression Scale.

Results
No genome-wide significant hits were observed. Suggestive (P < 1E-5) epigenome-wide evidence was discerned for altered DNA methylation at 6 CpG sites (LOC102724467, LOC100506023, RSPO2, SAG, IL16, PRKCI) to predict response to naturalistic antidepressant treatment. In patients treated with serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors, differential DNA methylation at 11 CpGs, for example, mapping to the TIMP2, VDAC1, or SORL1 genes, was suggestively associated with treatment response.

Conclusions
The present results provide preliminary evidence for altered DNA methylation patterns to be associated with antidepressant treatment response in MDD. Provided significant replication in independent and larger samples, the present findings might in the future aid in clinical decision-making toward more individualized and thus more efficacious treatments of MDD

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
The international journal of neuropsychopharmacology. - 27, 11 (2024) , pyae045, ISSN: 1469-5111

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2024
Urheber

DOI
10.1093/ijnp/pyae045
URN
urn:nbn:de:bsz:25-freidok-2575718
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:37 MESZ

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Beteiligte

Entstanden

  • 2024

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