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DNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive Therapy

BACKGROUND: Major depressive disorder (MDD) represents a tremendous health threat to the world’s population. Electroconvulsive therapy (ECT) is the most effective treatment option for refractory MDD patients. Ample evidence suggests brain-derived neurotrophic factor (BDNF) to play a crucial role in...

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Autores principales: Moschny, Nicole, Jahn, Kirsten, Bajbouj, Malek, Maier, Hannah Benedictine, Ballmaier, Matthias, Khan, Abdul Qayyum, Pollak, Christoph, Bleich, Stefan, Frieling, Helge, Neyazi, Alexandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319092/
https://www.ncbi.nlm.nih.gov/pubmed/32636772
http://dx.doi.org/10.3389/fpsyt.2020.00571
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author Moschny, Nicole
Jahn, Kirsten
Bajbouj, Malek
Maier, Hannah Benedictine
Ballmaier, Matthias
Khan, Abdul Qayyum
Pollak, Christoph
Bleich, Stefan
Frieling, Helge
Neyazi, Alexandra
author_facet Moschny, Nicole
Jahn, Kirsten
Bajbouj, Malek
Maier, Hannah Benedictine
Ballmaier, Matthias
Khan, Abdul Qayyum
Pollak, Christoph
Bleich, Stefan
Frieling, Helge
Neyazi, Alexandra
author_sort Moschny, Nicole
collection PubMed
description BACKGROUND: Major depressive disorder (MDD) represents a tremendous health threat to the world’s population. Electroconvulsive therapy (ECT) is the most effective treatment option for refractory MDD patients. Ample evidence suggests brain-derived neurotrophic factor (BDNF) to play a crucial role in ECT’s mode of action. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) are involved in BDNF production. HYPOTHESIS: The DNA methylation of gene regions encoding for t-PA and PAI-1 might be a suitable biomarker for ECT response prediction. METHODS: We withdrew blood from two cohorts of treatment-resistant MDD patients receiving ECT. In the first cohort (n = 59), blood was collected at baseline only. To evaluate DNA methylation changes throughout the treatment course, we acquired a second group (n = 28) and took blood samples at multiple time points. DNA isolated from whole blood and defined immune cell subtypes (B cells, monocytes, natural killer cells, and T cells) served for epigenetic analyses. RESULTS: Mixed linear models (corrected for multiple testing by Sidak’s post-hoc test) revealed (1) no detectable baseline blood DNA methylation differences between ECT remitters (n = 33) and non-remitters (n = 53) in the regions analyzed, but (2) a significant difference in t-PA’s DNA methylation between the investigated immune cell subtypes instead (p < 0.00001). This difference remained stable throughout the treatment course, showed no acute changes after ECT, and was independent of clinical remission. CONCLUSION: DNA methylation of both proteins seems to play a minor role in ECT’s mechanisms. Generally, we recommend using defined immune cell subtypes (instead of whole blood only) for DNA methylation analyses.
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spelling pubmed-73190922020-07-06 DNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive Therapy Moschny, Nicole Jahn, Kirsten Bajbouj, Malek Maier, Hannah Benedictine Ballmaier, Matthias Khan, Abdul Qayyum Pollak, Christoph Bleich, Stefan Frieling, Helge Neyazi, Alexandra Front Psychiatry Psychiatry BACKGROUND: Major depressive disorder (MDD) represents a tremendous health threat to the world’s population. Electroconvulsive therapy (ECT) is the most effective treatment option for refractory MDD patients. Ample evidence suggests brain-derived neurotrophic factor (BDNF) to play a crucial role in ECT’s mode of action. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) are involved in BDNF production. HYPOTHESIS: The DNA methylation of gene regions encoding for t-PA and PAI-1 might be a suitable biomarker for ECT response prediction. METHODS: We withdrew blood from two cohorts of treatment-resistant MDD patients receiving ECT. In the first cohort (n = 59), blood was collected at baseline only. To evaluate DNA methylation changes throughout the treatment course, we acquired a second group (n = 28) and took blood samples at multiple time points. DNA isolated from whole blood and defined immune cell subtypes (B cells, monocytes, natural killer cells, and T cells) served for epigenetic analyses. RESULTS: Mixed linear models (corrected for multiple testing by Sidak’s post-hoc test) revealed (1) no detectable baseline blood DNA methylation differences between ECT remitters (n = 33) and non-remitters (n = 53) in the regions analyzed, but (2) a significant difference in t-PA’s DNA methylation between the investigated immune cell subtypes instead (p < 0.00001). This difference remained stable throughout the treatment course, showed no acute changes after ECT, and was independent of clinical remission. CONCLUSION: DNA methylation of both proteins seems to play a minor role in ECT’s mechanisms. Generally, we recommend using defined immune cell subtypes (instead of whole blood only) for DNA methylation analyses. Frontiers Media S.A. 2020-06-19 /pmc/articles/PMC7319092/ /pubmed/32636772 http://dx.doi.org/10.3389/fpsyt.2020.00571 Text en Copyright © 2020 Moschny, Jahn, Bajbouj, Maier, Ballmaier, Khan, Pollak, Bleich, Frieling and Neyazi http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Moschny, Nicole
Jahn, Kirsten
Bajbouj, Malek
Maier, Hannah Benedictine
Ballmaier, Matthias
Khan, Abdul Qayyum
Pollak, Christoph
Bleich, Stefan
Frieling, Helge
Neyazi, Alexandra
DNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive Therapy
title DNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive Therapy
title_full DNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive Therapy
title_fullStr DNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive Therapy
title_full_unstemmed DNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive Therapy
title_short DNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive Therapy
title_sort dna methylation of the t-pa gene differs between various immune cell subtypes isolated from depressed patients receiving electroconvulsive therapy
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319092/
https://www.ncbi.nlm.nih.gov/pubmed/32636772
http://dx.doi.org/10.3389/fpsyt.2020.00571
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