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Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers
A significant proportion of the personal and economic burden of schizophrenia can be attributed to the late diagnosis or misdiagnosis of the disorder. A novel, objective diagnostic approaches could facilitate the early detection and treatment of schizophrenia and improve patient outcomes. In the pre...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618570/ https://www.ncbi.nlm.nih.gov/pubmed/36310155 http://dx.doi.org/10.1038/s41398-022-02229-w |
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author | Zaki, Jihan K. Lago, Santiago G. Rustogi, Nitin Gangadin, Shiral S. Benacek, Jiri van Rees, Geertje F. Haenisch, Frieder Broek, Jantine A. Suarez-Pinilla, Paula Ruland, Tillmann Auyeung, Bonnie Mikova, Olya Kabacs, Nikolett Arolt, Volker Baron-Cohen, Simon Crespo-Facorro, Benedicto Drexhage, Hemmo A. de Witte, Lot D. Kahn, René S. Sommer, Iris E. Bahn, Sabine Tomasik, Jakub |
author_facet | Zaki, Jihan K. Lago, Santiago G. Rustogi, Nitin Gangadin, Shiral S. Benacek, Jiri van Rees, Geertje F. Haenisch, Frieder Broek, Jantine A. Suarez-Pinilla, Paula Ruland, Tillmann Auyeung, Bonnie Mikova, Olya Kabacs, Nikolett Arolt, Volker Baron-Cohen, Simon Crespo-Facorro, Benedicto Drexhage, Hemmo A. de Witte, Lot D. Kahn, René S. Sommer, Iris E. Bahn, Sabine Tomasik, Jakub |
author_sort | Zaki, Jihan K. |
collection | PubMed |
description | A significant proportion of the personal and economic burden of schizophrenia can be attributed to the late diagnosis or misdiagnosis of the disorder. A novel, objective diagnostic approaches could facilitate the early detection and treatment of schizophrenia and improve patient outcomes. In the present study, we aimed to identify robust schizophrenia-specific blood biomarkers, with the goal of developing an accurate diagnostic model. The levels of selected serum and peripheral blood mononuclear cell (PBMC) markers relevant to metabolic and immune function were measured in healthy controls (n = 26) and recent-onset schizophrenia patients (n = 36) using multiplexed immunoassays and flow cytometry. Analysis of covariance revealed significant upregulation of insulin receptor (IR) and fatty acid translocase (CD36) levels in T helper cells (F = 10.75, P = 0.002, Q = 0.024 and F = 21.58, P = 2.8 × 10(−5), Q = 0.0004, respectively), as well as downregulation of glucose transporter 1 (GLUT1) expression in monocytes (F = 21.46, P = 2.9 × 10(−5), Q = 0.0004). The most robust predictors, monocyte GLUT1 and T helper cell CD36, were used to develop a diagnostic model, which showed a leave-one-out cross-validated area under the receiver operating characteristic curve (AUC) of 0.78 (95% CI: 0.66–0.92). The diagnostic model was validated in two independent datasets. The model was able to distinguish first-onset, drug-naïve schizophrenia patients (n = 34) from healthy controls (n = 39) with an AUC of 0.75 (95% CI: 0.64–0.86), and also differentiated schizophrenia patients (n = 22) from patients with other neuropsychiatric conditions, including bipolar disorder, major depressive disorder and autism spectrum disorder (n = 68), with an AUC of 0.83 (95% CI: 0.75–0.92). These findings indicate that PBMC-derived biomarkers have the potential to support an accurate and objective differential diagnosis of schizophrenia. |
format | Online Article Text |
id | pubmed-9618570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96185702022-11-01 Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers Zaki, Jihan K. Lago, Santiago G. Rustogi, Nitin Gangadin, Shiral S. Benacek, Jiri van Rees, Geertje F. Haenisch, Frieder Broek, Jantine A. Suarez-Pinilla, Paula Ruland, Tillmann Auyeung, Bonnie Mikova, Olya Kabacs, Nikolett Arolt, Volker Baron-Cohen, Simon Crespo-Facorro, Benedicto Drexhage, Hemmo A. de Witte, Lot D. Kahn, René S. Sommer, Iris E. Bahn, Sabine Tomasik, Jakub Transl Psychiatry Article A significant proportion of the personal and economic burden of schizophrenia can be attributed to the late diagnosis or misdiagnosis of the disorder. A novel, objective diagnostic approaches could facilitate the early detection and treatment of schizophrenia and improve patient outcomes. In the present study, we aimed to identify robust schizophrenia-specific blood biomarkers, with the goal of developing an accurate diagnostic model. The levels of selected serum and peripheral blood mononuclear cell (PBMC) markers relevant to metabolic and immune function were measured in healthy controls (n = 26) and recent-onset schizophrenia patients (n = 36) using multiplexed immunoassays and flow cytometry. Analysis of covariance revealed significant upregulation of insulin receptor (IR) and fatty acid translocase (CD36) levels in T helper cells (F = 10.75, P = 0.002, Q = 0.024 and F = 21.58, P = 2.8 × 10(−5), Q = 0.0004, respectively), as well as downregulation of glucose transporter 1 (GLUT1) expression in monocytes (F = 21.46, P = 2.9 × 10(−5), Q = 0.0004). The most robust predictors, monocyte GLUT1 and T helper cell CD36, were used to develop a diagnostic model, which showed a leave-one-out cross-validated area under the receiver operating characteristic curve (AUC) of 0.78 (95% CI: 0.66–0.92). The diagnostic model was validated in two independent datasets. The model was able to distinguish first-onset, drug-naïve schizophrenia patients (n = 34) from healthy controls (n = 39) with an AUC of 0.75 (95% CI: 0.64–0.86), and also differentiated schizophrenia patients (n = 22) from patients with other neuropsychiatric conditions, including bipolar disorder, major depressive disorder and autism spectrum disorder (n = 68), with an AUC of 0.83 (95% CI: 0.75–0.92). These findings indicate that PBMC-derived biomarkers have the potential to support an accurate and objective differential diagnosis of schizophrenia. Nature Publishing Group UK 2022-10-30 /pmc/articles/PMC9618570/ /pubmed/36310155 http://dx.doi.org/10.1038/s41398-022-02229-w Text en © The Author(s) 2022 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 Zaki, Jihan K. Lago, Santiago G. Rustogi, Nitin Gangadin, Shiral S. Benacek, Jiri van Rees, Geertje F. Haenisch, Frieder Broek, Jantine A. Suarez-Pinilla, Paula Ruland, Tillmann Auyeung, Bonnie Mikova, Olya Kabacs, Nikolett Arolt, Volker Baron-Cohen, Simon Crespo-Facorro, Benedicto Drexhage, Hemmo A. de Witte, Lot D. Kahn, René S. Sommer, Iris E. Bahn, Sabine Tomasik, Jakub Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers |
title | Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers |
title_full | Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers |
title_fullStr | Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers |
title_full_unstemmed | Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers |
title_short | Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers |
title_sort | diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618570/ https://www.ncbi.nlm.nih.gov/pubmed/36310155 http://dx.doi.org/10.1038/s41398-022-02229-w |
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