DNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive Therapy
BackgroundMajor 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 EC...
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fpsyt.2020.00571/full |
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| author | Nicole Moschny Nicole Moschny Kirsten Jahn Malek Bajbouj Hannah Benedictine Maier Matthias Ballmaier Abdul Qayyum Khan Christoph Pollak Stefan Bleich Stefan Bleich Helge Frieling Helge Frieling Helge Frieling Alexandra Neyazi Alexandra Neyazi |
| author_facet | Nicole Moschny Nicole Moschny Kirsten Jahn Malek Bajbouj Hannah Benedictine Maier Matthias Ballmaier Abdul Qayyum Khan Christoph Pollak Stefan Bleich Stefan Bleich Helge Frieling Helge Frieling Helge Frieling Alexandra Neyazi Alexandra Neyazi |
| author_sort | Nicole Moschny |
| collection | DOAJ |
| description | BackgroundMajor 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.HypothesisThe DNA methylation of gene regions encoding for t-PA and PAI-1 might be a suitable biomarker for ECT response prediction.MethodsWe 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.ResultsMixed 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.ConclusionDNA 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. |
| first_indexed | 2024-12-11T11:08:33Z |
| format | Article |
| id | doaj.art-02b9033e0f3045738afc458aa153d9e7 |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-11T11:08:33Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Psychiatry |
| spelling | doaj.art-02b9033e0f3045738afc458aa153d9e72022-12-22T01:09:38ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402020-06-011110.3389/fpsyt.2020.00571512202DNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive TherapyNicole Moschny0Nicole Moschny1Kirsten Jahn2Malek Bajbouj3Hannah Benedictine Maier4Matthias Ballmaier5Abdul Qayyum Khan6Christoph Pollak7Stefan Bleich8Stefan Bleich9Helge Frieling10Helge Frieling11Helge Frieling12Alexandra Neyazi13Alexandra Neyazi14Laboratory for Molecular Neurosciences, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyCenter for Systems Neuroscience, Hannover Graduate School for Veterinary Pathobiology, Neuroinfectiology, and Translational Medicine (HGNI), Hannover, GermanyLaboratory for Molecular Neurosciences, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyDepartment of Psychiatry and Psychotherapy, Charité, Berlin, GermanyDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyCell Sorting Core Facility, Hannover Medical School, Hannover, GermanyLaboratory for Molecular Neurosciences, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyCenter for Systems Neuroscience, Hannover Graduate School for Veterinary Pathobiology, Neuroinfectiology, and Translational Medicine (HGNI), Hannover, GermanyDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyLaboratory for Molecular Neurosciences, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyCenter for Systems Neuroscience, Hannover Graduate School for Veterinary Pathobiology, Neuroinfectiology, and Translational Medicine (HGNI), Hannover, GermanyDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyCenter for Systems Neuroscience, Hannover Graduate School for Veterinary Pathobiology, Neuroinfectiology, and Translational Medicine (HGNI), Hannover, GermanyDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyBackgroundMajor 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.HypothesisThe DNA methylation of gene regions encoding for t-PA and PAI-1 might be a suitable biomarker for ECT response prediction.MethodsWe 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.ResultsMixed 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.ConclusionDNA 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.https://www.frontiersin.org/article/10.3389/fpsyt.2020.00571/fullbrain-derived neurotrophic factortissue-type plasminogen activatordepressionimmunologyDNA methylationelectroconvulsive therapy remission |
| spellingShingle | Nicole Moschny Nicole Moschny Kirsten Jahn Malek Bajbouj Hannah Benedictine Maier Matthias Ballmaier Abdul Qayyum Khan Christoph Pollak Stefan Bleich Stefan Bleich Helge Frieling Helge Frieling Helge Frieling Alexandra Neyazi Alexandra Neyazi DNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive Therapy Frontiers in Psychiatry brain-derived neurotrophic factor tissue-type plasminogen activator depression immunology DNA methylation electroconvulsive therapy remission |
| 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 | brain-derived neurotrophic factor tissue-type plasminogen activator depression immunology DNA methylation electroconvulsive therapy remission |
| url | https://www.frontiersin.org/article/10.3389/fpsyt.2020.00571/full |
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