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Upregulation of sICAM-1 and sVCAM-1 Levels in the Cerebrospinal Fluid of Patients with Schizophrenia Spectrum Disorders

Immunological explanatory approaches are becoming increasingly important in schizophrenia research. In this context, the function of the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) plays an essential role. Different adhesion molecules, such as intercellular adhe...

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Autores principales: Meixensberger, Sophie, Kuzior, Hanna, Fiebich, Bernd L., Süß, Patrick, Runge, Kimon, Berger, Benjamin, Nickel, Kathrin, Denzel, Dominik, Schiele, Miriam A., Michel, Maike, Maier, Simon, Bechter, Karl, Domschke, Katharina, Tebartz van Elst, Ludger, Endres, Dominique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307568/
https://www.ncbi.nlm.nih.gov/pubmed/34206599
http://dx.doi.org/10.3390/diagnostics11071134
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author Meixensberger, Sophie
Kuzior, Hanna
Fiebich, Bernd L.
Süß, Patrick
Runge, Kimon
Berger, Benjamin
Nickel, Kathrin
Denzel, Dominik
Schiele, Miriam A.
Michel, Maike
Maier, Simon
Bechter, Karl
Domschke, Katharina
Tebartz van Elst, Ludger
Endres, Dominique
author_facet Meixensberger, Sophie
Kuzior, Hanna
Fiebich, Bernd L.
Süß, Patrick
Runge, Kimon
Berger, Benjamin
Nickel, Kathrin
Denzel, Dominik
Schiele, Miriam A.
Michel, Maike
Maier, Simon
Bechter, Karl
Domschke, Katharina
Tebartz van Elst, Ludger
Endres, Dominique
author_sort Meixensberger, Sophie
collection PubMed
description Immunological explanatory approaches are becoming increasingly important in schizophrenia research. In this context, the function of the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) plays an essential role. Different adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), are key elements in sustaining the integrity of the BBB and BCSFB. The objectives of this study were to (1) compare the levels of different cell adhesion molecules in the CSF of patients with schizophrenia spectrum disorders to those of patients with unipolar depression and (2) analyze their association with the established markers of the BBB/BCSFB function (CSF total protein and albumin quotient (AQ)). Therefore, a total of 40 patients with schizophrenia spectrum disorder and 39 age- and sex-matched control patients with unipolar depression were analyzed. The levels of soluble ICAM-1 (s-ICAM-1), soluble VCAM-1 (s-VCAM-1), and plasminogen activator inhibitor 1 (PAI-1) in the CSF were measured using a magnetic bead multiplexing immunoassay. The levels of sICAM-1 (p < 0.001), sVCAM-1 (p < 0.001), and PAI-1 (p < 0.001) in the CSF were significantly higher in patients with schizophrenia spectrum disorder than in patients with unipolar depression. In addition, a significant correlation of sVCAM-1 levels with total protein concentrations (r = 0.454, p = 0.003) and AQ levels (r = 0.512, p = 0.001) in patients with schizophrenia spectrum disorders was observed. The results revealed that sICAM-1 and sVCAM-1 levels in the CSF were higher in patients with schizophrenia spectrum disorder than in those with depression. These circulating signaling molecules may indicate endothelial dysfunction causing impaired BBB/BCSFB function in patients with schizophrenia spectrum disorders. Consistent with this view, a highly significant correlation of sVCAM-1 with CSF protein and AQs was detected. Upregulation of these cell adhesion molecules might be indicative of a proinflammatory immune response underlying the BBB/BCSFB disturbance in a subgroup of patients with schizophrenia spectrum disorders. The significance of the study is limited by its retrospective research design and by the absence of a healthy control group. The assay used was not previously established for the measurement of CSF. Further translational and controlled studies of the role of different cell adhesion molecules in schizophrenia are needed.
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spelling pubmed-83075682021-07-25 Upregulation of sICAM-1 and sVCAM-1 Levels in the Cerebrospinal Fluid of Patients with Schizophrenia Spectrum Disorders Meixensberger, Sophie Kuzior, Hanna Fiebich, Bernd L. Süß, Patrick Runge, Kimon Berger, Benjamin Nickel, Kathrin Denzel, Dominik Schiele, Miriam A. Michel, Maike Maier, Simon Bechter, Karl Domschke, Katharina Tebartz van Elst, Ludger Endres, Dominique Diagnostics (Basel) Article Immunological explanatory approaches are becoming increasingly important in schizophrenia research. In this context, the function of the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) plays an essential role. Different adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), are key elements in sustaining the integrity of the BBB and BCSFB. The objectives of this study were to (1) compare the levels of different cell adhesion molecules in the CSF of patients with schizophrenia spectrum disorders to those of patients with unipolar depression and (2) analyze their association with the established markers of the BBB/BCSFB function (CSF total protein and albumin quotient (AQ)). Therefore, a total of 40 patients with schizophrenia spectrum disorder and 39 age- and sex-matched control patients with unipolar depression were analyzed. The levels of soluble ICAM-1 (s-ICAM-1), soluble VCAM-1 (s-VCAM-1), and plasminogen activator inhibitor 1 (PAI-1) in the CSF were measured using a magnetic bead multiplexing immunoassay. The levels of sICAM-1 (p < 0.001), sVCAM-1 (p < 0.001), and PAI-1 (p < 0.001) in the CSF were significantly higher in patients with schizophrenia spectrum disorder than in patients with unipolar depression. In addition, a significant correlation of sVCAM-1 levels with total protein concentrations (r = 0.454, p = 0.003) and AQ levels (r = 0.512, p = 0.001) in patients with schizophrenia spectrum disorders was observed. The results revealed that sICAM-1 and sVCAM-1 levels in the CSF were higher in patients with schizophrenia spectrum disorder than in those with depression. These circulating signaling molecules may indicate endothelial dysfunction causing impaired BBB/BCSFB function in patients with schizophrenia spectrum disorders. Consistent with this view, a highly significant correlation of sVCAM-1 with CSF protein and AQs was detected. Upregulation of these cell adhesion molecules might be indicative of a proinflammatory immune response underlying the BBB/BCSFB disturbance in a subgroup of patients with schizophrenia spectrum disorders. The significance of the study is limited by its retrospective research design and by the absence of a healthy control group. The assay used was not previously established for the measurement of CSF. Further translational and controlled studies of the role of different cell adhesion molecules in schizophrenia are needed. MDPI 2021-06-22 /pmc/articles/PMC8307568/ /pubmed/34206599 http://dx.doi.org/10.3390/diagnostics11071134 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Meixensberger, Sophie
Kuzior, Hanna
Fiebich, Bernd L.
Süß, Patrick
Runge, Kimon
Berger, Benjamin
Nickel, Kathrin
Denzel, Dominik
Schiele, Miriam A.
Michel, Maike
Maier, Simon
Bechter, Karl
Domschke, Katharina
Tebartz van Elst, Ludger
Endres, Dominique
Upregulation of sICAM-1 and sVCAM-1 Levels in the Cerebrospinal Fluid of Patients with Schizophrenia Spectrum Disorders
title Upregulation of sICAM-1 and sVCAM-1 Levels in the Cerebrospinal Fluid of Patients with Schizophrenia Spectrum Disorders
title_full Upregulation of sICAM-1 and sVCAM-1 Levels in the Cerebrospinal Fluid of Patients with Schizophrenia Spectrum Disorders
title_fullStr Upregulation of sICAM-1 and sVCAM-1 Levels in the Cerebrospinal Fluid of Patients with Schizophrenia Spectrum Disorders
title_full_unstemmed Upregulation of sICAM-1 and sVCAM-1 Levels in the Cerebrospinal Fluid of Patients with Schizophrenia Spectrum Disorders
title_short Upregulation of sICAM-1 and sVCAM-1 Levels in the Cerebrospinal Fluid of Patients with Schizophrenia Spectrum Disorders
title_sort upregulation of sicam-1 and svcam-1 levels in the cerebrospinal fluid of patients with schizophrenia spectrum disorders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307568/
https://www.ncbi.nlm.nih.gov/pubmed/34206599
http://dx.doi.org/10.3390/diagnostics11071134
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