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CC BY-NC-ND 4.0 · Pharmacopsychiatry 2023; 56(02): 64-72
DOI: 10.1055/a-2034-6536
Original Paper

DNA Methylation of POMC and NR3C1-1F and Its Implication in Major Depressive Disorder and Electroconvulsive Therapy

Hannah B. Maier   *   *
1   Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Hannover, Germany
,
Nicole Moschny   *
2   Laboratory for Molecular Neuroscience, Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Hannover, Germany
,
Franziska Eberle
1   Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Hannover, Germany
,
Kirsten Jahn
2   Laboratory for Molecular Neuroscience, Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Hannover, Germany
,
Thorsten Folsche
1   Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Hannover, Germany
,
Rasmus Schülke
1   Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Hannover, Germany
,
Stefan Bleich
1   Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Hannover, Germany
2   Laboratory for Molecular Neuroscience, Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Hannover, Germany
,
Helge Frieling
1   Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Hannover, Germany
2   Laboratory for Molecular Neuroscience, Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Hannover, Germany
,
Alexandra Neyazi
2   Laboratory for Molecular Neuroscience, Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Hannover, Germany
3   Department of Psychiatry and Psychotherapy, Otto von Guericke University Magdeburg (OVGU), Germany
› Author Affiliations Funding Information This project was supported by PRACTIS-Clinician Scientist Program of Hannover Medical School, funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, ME3696/3-1) – Project- ID 413617135 and in-house funding from Hannover Medical School.
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Abstract

Introduction Precision medicine in psychiatry is still in its infancy. To establish patient-tailored treatment, adequate indicators predicting treatment response are required. Electroconvulsive therapy (ECT) is considered one of the most effective options for pharmacoresistant major depressive disorder (MDD), yet remission rates were reported to be below 50%.

Methods Since epigenetics of the stress response system seem to play a role in MDD, we analyzed the DNA methylation (DNAm) of genes encoding the glucocorticoid receptor (NR3C1) and proopiomelanocortin (POMC) through Sanger Sequencing. For analysis, blood was taken before and after the first and last ECT from MDD patients (n=31), unmedicated depressed controls (UDC; n=19, baseline), and healthy controls (HC; n=20, baseline).

Results Baseline DNAm in NR3C1 was significantly lower in UDCs compared to both other groups (UDC: 0.014(±0.002), ECT: 0.031(±0.001), HC: 0.024(±0.002); p<0.001), whereas regarding POMC, ECT patients had the highest DNAm levels (ECT: 0.252(±0.013), UDC: 0.156(±0.015), HC: 0.162(±0.014); p<0.001). NR3C1m and POMCm decreased after the first ECT (NR3C1: p<0.001; POMC: p=0.001), and responders were less methylated compared to non-responders in NR3C1(p<0.001).

Discussion Our findings indicate that both genes might play a role in the chronification of depression and NR3C1 may be relevant for ECT response prediction.

Key words

electroconvulsive therapy - epigenetics - DNA methylation - proopiomelanocortin - NR3C1 - hypothalamic-pituitary-adrenal axis

* These authors share the first authorship


Supplementary Material



Publication History

Received: 13 June 2022
Received: 27 December 2022

Accepted: 06 February 2023

Article published online:
21 March 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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