DNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive Therapy.
DNA methylation
brain-derived neurotrophic factor
depression
electroconvulsive therapy remission
immunology
tissue-type plasminogen activator
Journal
Frontiers in psychiatry
ISSN: 1664-0640
Titre abrégé: Front Psychiatry
Pays: Switzerland
ID NLM: 101545006
Informations de publication
Date de publication:
2020
2020
Historique:
received:
14
11
2019
accepted:
03
06
2020
entrez:
9
7
2020
pubmed:
9
7
2020
medline:
9
7
2020
Statut:
epublish
Résumé
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. The DNA methylation of gene regions encoding for t-PA and PAI-1 might be a suitable biomarker for ECT response prediction. 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. 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. 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
The DNA methylation of gene regions encoding for t-PA and PAI-1 might be a suitable biomarker for ECT response prediction.
METHODS
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 32636772
doi: 10.3389/fpsyt.2020.00571
pmc: PMC7319092
doi:
Types de publication
Journal Article
Langues
eng
Pagination
571Informations de copyright
Copyright © 2020 Moschny, Jahn, Bajbouj, Maier, Ballmaier, Khan, Pollak, Bleich, Frieling and Neyazi.
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