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Increased GFAP concentrations in the cerebrospinal fluid of patients with unipolar depression

Inflammatory processes involving altered microglial activity may play a relevant role in the pathophysiology of depressive disorders. Glial fibrillary acidic protein (GFAP) and calcium-binding protein S100B are considered microglial markers. To date, their role has been studied in the serum and tiss...

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Autores principales: Michel, Maike, Fiebich, Bernd L., Kuzior, Hanna, Meixensberger, Sophie, Berger, Benjamin, Maier, Simon, Nickel, Kathrin, Runge, Kimon, Denzel, Dominik, Pankratz, Benjamin, Schiele, Miriam A., Domschke, Katharina, van Elst, Ludger Tebartz, Endres, Dominique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139962/
https://www.ncbi.nlm.nih.gov/pubmed/34021122
http://dx.doi.org/10.1038/s41398-021-01423-6
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author Michel, Maike
Fiebich, Bernd L.
Kuzior, Hanna
Meixensberger, Sophie
Berger, Benjamin
Maier, Simon
Nickel, Kathrin
Runge, Kimon
Denzel, Dominik
Pankratz, Benjamin
Schiele, Miriam A.
Domschke, Katharina
van Elst, Ludger Tebartz
Endres, Dominique
author_facet Michel, Maike
Fiebich, Bernd L.
Kuzior, Hanna
Meixensberger, Sophie
Berger, Benjamin
Maier, Simon
Nickel, Kathrin
Runge, Kimon
Denzel, Dominik
Pankratz, Benjamin
Schiele, Miriam A.
Domschke, Katharina
van Elst, Ludger Tebartz
Endres, Dominique
author_sort Michel, Maike
collection PubMed
description Inflammatory processes involving altered microglial activity may play a relevant role in the pathophysiology of depressive disorders. Glial fibrillary acidic protein (GFAP) and calcium-binding protein S100B are considered microglial markers. To date, their role has been studied in the serum and tissue material of patients with unipolar depression but not in the cerebrospinal fluid (CSF). Therefore, the aim of the current study was to examine GFAP and S100B levels in the CSF of patients with major depression to better understand their role in affective disorders. In this retrospective study, 102 patients with unipolar depression and 39 mentally healthy controls with idiopathic intracranial hypertension were investigated. GFAP and S100B levels were measured using commercially available ELISA kits. CSF routine parameters were collected during routine clinical care. The mean values of GFAP and S100B were compared using age (and sex) corrected ANOVAs. Matched subgroups were analyzed by using an independent sample t-test. In addition, correlation analyses between GFAP/S100B levels and CSF routine parameters were performed within the patient group. Patients with unipolar depression had significantly higher levels of GFAP than controls (733.22 pg/ml vs. 245.56 pg/ml, p < 0.001). These results remained significant in a sub-analysis in which all controls were compared with patients suffering from depression matched 1:1 by age and sex (632.26 pg/ml vs. 245.56 pg/ml, p < 0.001). Levels of S100B did not differ significantly between patients and controls (1.06 ng/ml vs. 1.17 ng/ml, p = 0.385). GFAP levels correlated positively with albumin quotients (p < 0.050), S100B levels correlated positively with white blood cell counts (p = 0.001), total protein concentrations (p < 0.001), and albumin quotients (p = 0.001) in the CSF. The significance of the study is limited by its retrospective and open design, methodological aspects, and the control group with idiopathic intracranial hypertension. In conclusion, higher GFAP levels in patients with depression may be indicative of altered microglia activity, especially in astrocytes, in patients with unipolar depression. In addition, correlation analyses support the idea that S100B levels could be related to the integrity of the blood–brain/CSF barrier. Further multimodal and longitudinal studies are necessary to validate these findings and clarify the underlying biological processes.
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spelling pubmed-81399622021-06-03 Increased GFAP concentrations in the cerebrospinal fluid of patients with unipolar depression Michel, Maike Fiebich, Bernd L. Kuzior, Hanna Meixensberger, Sophie Berger, Benjamin Maier, Simon Nickel, Kathrin Runge, Kimon Denzel, Dominik Pankratz, Benjamin Schiele, Miriam A. Domschke, Katharina van Elst, Ludger Tebartz Endres, Dominique Transl Psychiatry Article Inflammatory processes involving altered microglial activity may play a relevant role in the pathophysiology of depressive disorders. Glial fibrillary acidic protein (GFAP) and calcium-binding protein S100B are considered microglial markers. To date, their role has been studied in the serum and tissue material of patients with unipolar depression but not in the cerebrospinal fluid (CSF). Therefore, the aim of the current study was to examine GFAP and S100B levels in the CSF of patients with major depression to better understand their role in affective disorders. In this retrospective study, 102 patients with unipolar depression and 39 mentally healthy controls with idiopathic intracranial hypertension were investigated. GFAP and S100B levels were measured using commercially available ELISA kits. CSF routine parameters were collected during routine clinical care. The mean values of GFAP and S100B were compared using age (and sex) corrected ANOVAs. Matched subgroups were analyzed by using an independent sample t-test. In addition, correlation analyses between GFAP/S100B levels and CSF routine parameters were performed within the patient group. Patients with unipolar depression had significantly higher levels of GFAP than controls (733.22 pg/ml vs. 245.56 pg/ml, p < 0.001). These results remained significant in a sub-analysis in which all controls were compared with patients suffering from depression matched 1:1 by age and sex (632.26 pg/ml vs. 245.56 pg/ml, p < 0.001). Levels of S100B did not differ significantly between patients and controls (1.06 ng/ml vs. 1.17 ng/ml, p = 0.385). GFAP levels correlated positively with albumin quotients (p < 0.050), S100B levels correlated positively with white blood cell counts (p = 0.001), total protein concentrations (p < 0.001), and albumin quotients (p = 0.001) in the CSF. The significance of the study is limited by its retrospective and open design, methodological aspects, and the control group with idiopathic intracranial hypertension. In conclusion, higher GFAP levels in patients with depression may be indicative of altered microglia activity, especially in astrocytes, in patients with unipolar depression. In addition, correlation analyses support the idea that S100B levels could be related to the integrity of the blood–brain/CSF barrier. Further multimodal and longitudinal studies are necessary to validate these findings and clarify the underlying biological processes. Nature Publishing Group UK 2021-05-21 /pmc/articles/PMC8139962/ /pubmed/34021122 http://dx.doi.org/10.1038/s41398-021-01423-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Michel, Maike
Fiebich, Bernd L.
Kuzior, Hanna
Meixensberger, Sophie
Berger, Benjamin
Maier, Simon
Nickel, Kathrin
Runge, Kimon
Denzel, Dominik
Pankratz, Benjamin
Schiele, Miriam A.
Domschke, Katharina
van Elst, Ludger Tebartz
Endres, Dominique
Increased GFAP concentrations in the cerebrospinal fluid of patients with unipolar depression
title Increased GFAP concentrations in the cerebrospinal fluid of patients with unipolar depression
title_full Increased GFAP concentrations in the cerebrospinal fluid of patients with unipolar depression
title_fullStr Increased GFAP concentrations in the cerebrospinal fluid of patients with unipolar depression
title_full_unstemmed Increased GFAP concentrations in the cerebrospinal fluid of patients with unipolar depression
title_short Increased GFAP concentrations in the cerebrospinal fluid of patients with unipolar depression
title_sort increased gfap concentrations in the cerebrospinal fluid of patients with unipolar depression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139962/
https://www.ncbi.nlm.nih.gov/pubmed/34021122
http://dx.doi.org/10.1038/s41398-021-01423-6
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