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Novel candidate genes for ECT response prediction—a pilot study analyzing the DNA methylome of depressed patients receiving electroconvulsive therapy
BACKGROUND: Major depressive disorder (MDD) represents a serious global health concern. The urge for efficient MDD treatment strategies is presently hindered by the incomplete knowledge of its underlying pathomechanism. Despite recent progress (highlighting both genetics and the environment, and thu...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388224/ https://www.ncbi.nlm.nih.gov/pubmed/32727556 http://dx.doi.org/10.1186/s13148-020-00891-9 |
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author | Moschny, Nicole Zindler, Tristan Jahn, Kirsten Dorda, Marie Davenport, Colin F. Wiehlmann, Lutz Maier, Hannah B. Eberle, Franziska Bleich, Stefan Neyazi, Alexandra Frieling, Helge |
author_facet | Moschny, Nicole Zindler, Tristan Jahn, Kirsten Dorda, Marie Davenport, Colin F. Wiehlmann, Lutz Maier, Hannah B. Eberle, Franziska Bleich, Stefan Neyazi, Alexandra Frieling, Helge |
author_sort | Moschny, Nicole |
collection | PubMed |
description | BACKGROUND: Major depressive disorder (MDD) represents a serious global health concern. The urge for efficient MDD treatment strategies is presently hindered by the incomplete knowledge of its underlying pathomechanism. Despite recent progress (highlighting both genetics and the environment, and thus DNA methylation, to be relevant for its development), 30–50% of MDD patients still fail to reach remission with standard treatment approaches. Electroconvulsive therapy (ECT) is one of the most powerful options for the treatment of pharmacoresistant depression; nevertheless, ECT remission rates barely reach 50% in large-scale naturalistic population-based studies. To optimize MDD treatment strategies and enable personalized medicine in the long- term, prospective indicators of ECT response are thus in great need. Because recent target-driven analyses revealed DNA methylation baseline differences between ECT responder groups, we analyzed the DNA methylome of depressed ECT patients using next-generation sequencing. In this pilot study, we did not only aim to find novel targets for ECT response prediction but also to get a deeper insight into its possible mechanism of action. RESULTS: Longitudinal DNA methylation analysis of peripheral blood mononuclear cells isolated from a cohort of treatment-resistant MDD patients (n = 12; time points: before and after 1st and last ECT, respectively) using a TruSeq-Methyl Capture EPIC Kit for library preparation, led to the following results: (1) The global DNA methylation differed neither between the four measured time points nor between ECT responders (n = 8) and non-responders (n = 4). (2) Analyzing the DNA methylation variance for every probe (=1476812 single CpG sites) revealed eight novel candidate genes to be implicated in ECT response (protein-coding genes: RNF175, RNF213, TBC1D14, TMC5, WSCD1; genes encoding for putative long non-coding RNA transcripts: AC018685.2, AC098617.1, CLCN3P1). (3) In addition, DNA methylation of two CpG sites (located within AQP10 and TRERF1) was found to change during the treatment course. CONCLUSIONS: We suggest ten novel candidate genes to be implicated in either ECT response or its possible mechanism. Because of the small sample size of our pilot study, our findings must be regarded as preliminary. |
format | Online Article Text |
id | pubmed-7388224 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-73882242020-07-31 Novel candidate genes for ECT response prediction—a pilot study analyzing the DNA methylome of depressed patients receiving electroconvulsive therapy Moschny, Nicole Zindler, Tristan Jahn, Kirsten Dorda, Marie Davenport, Colin F. Wiehlmann, Lutz Maier, Hannah B. Eberle, Franziska Bleich, Stefan Neyazi, Alexandra Frieling, Helge Clin Epigenetics Research BACKGROUND: Major depressive disorder (MDD) represents a serious global health concern. The urge for efficient MDD treatment strategies is presently hindered by the incomplete knowledge of its underlying pathomechanism. Despite recent progress (highlighting both genetics and the environment, and thus DNA methylation, to be relevant for its development), 30–50% of MDD patients still fail to reach remission with standard treatment approaches. Electroconvulsive therapy (ECT) is one of the most powerful options for the treatment of pharmacoresistant depression; nevertheless, ECT remission rates barely reach 50% in large-scale naturalistic population-based studies. To optimize MDD treatment strategies and enable personalized medicine in the long- term, prospective indicators of ECT response are thus in great need. Because recent target-driven analyses revealed DNA methylation baseline differences between ECT responder groups, we analyzed the DNA methylome of depressed ECT patients using next-generation sequencing. In this pilot study, we did not only aim to find novel targets for ECT response prediction but also to get a deeper insight into its possible mechanism of action. RESULTS: Longitudinal DNA methylation analysis of peripheral blood mononuclear cells isolated from a cohort of treatment-resistant MDD patients (n = 12; time points: before and after 1st and last ECT, respectively) using a TruSeq-Methyl Capture EPIC Kit for library preparation, led to the following results: (1) The global DNA methylation differed neither between the four measured time points nor between ECT responders (n = 8) and non-responders (n = 4). (2) Analyzing the DNA methylation variance for every probe (=1476812 single CpG sites) revealed eight novel candidate genes to be implicated in ECT response (protein-coding genes: RNF175, RNF213, TBC1D14, TMC5, WSCD1; genes encoding for putative long non-coding RNA transcripts: AC018685.2, AC098617.1, CLCN3P1). (3) In addition, DNA methylation of two CpG sites (located within AQP10 and TRERF1) was found to change during the treatment course. CONCLUSIONS: We suggest ten novel candidate genes to be implicated in either ECT response or its possible mechanism. Because of the small sample size of our pilot study, our findings must be regarded as preliminary. BioMed Central 2020-07-29 /pmc/articles/PMC7388224/ /pubmed/32727556 http://dx.doi.org/10.1186/s13148-020-00891-9 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Moschny, Nicole Zindler, Tristan Jahn, Kirsten Dorda, Marie Davenport, Colin F. Wiehlmann, Lutz Maier, Hannah B. Eberle, Franziska Bleich, Stefan Neyazi, Alexandra Frieling, Helge Novel candidate genes for ECT response prediction—a pilot study analyzing the DNA methylome of depressed patients receiving electroconvulsive therapy |
title | Novel candidate genes for ECT response prediction—a pilot study analyzing the DNA methylome of depressed patients receiving electroconvulsive therapy |
title_full | Novel candidate genes for ECT response prediction—a pilot study analyzing the DNA methylome of depressed patients receiving electroconvulsive therapy |
title_fullStr | Novel candidate genes for ECT response prediction—a pilot study analyzing the DNA methylome of depressed patients receiving electroconvulsive therapy |
title_full_unstemmed | Novel candidate genes for ECT response prediction—a pilot study analyzing the DNA methylome of depressed patients receiving electroconvulsive therapy |
title_short | Novel candidate genes for ECT response prediction—a pilot study analyzing the DNA methylome of depressed patients receiving electroconvulsive therapy |
title_sort | novel candidate genes for ect response prediction—a pilot study analyzing the dna methylome of depressed patients receiving electroconvulsive therapy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388224/ https://www.ncbi.nlm.nih.gov/pubmed/32727556 http://dx.doi.org/10.1186/s13148-020-00891-9 |
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