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Up-Regulation of S100 Gene Family in Brain Samples of a Subgroup of Individuals with Schizophrenia: Meta-analysis

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Abstract

The S100 proteins family is known to affect neuroinflammation and astrocyte activation, which have been suggested to be contributors to the pathogenesis of schizophrenia. We conducted a systematic meta-analysis of S100 genes differential expression in postmortem samples of patients with schizophrenia vs. healthy controls, following the commonly used Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Twelve microarray datasets met the inclusion criteria (overall 511 samples, 253 schizophrenia and 258 controls were analyzed). Nine out of 21 genes were significantly up-regulated or with tendency for up-regulation. A per-sample fold change analysis indicated that the S100 genes’ up-regulation was concentrated in a subgroup of the patients. None of the genes have been found to be down-regulated. ANXA3, which encodes Annexin 3 protein and was associated with neuroinflammation, was up-regulated and positively correlated with the S100 genes’ expression pattern. In addition, astrocytes and endothelial cell markers were significantly correlated with S100A8 expression. S100 correlation with ANXA3 and endothelial cell markers suggests that the up-regulation we detected reflects increased inflammation. However, it might also reflect astrocytes abundance or activation. The fact that S100 proteins were shown to be up-regulated in blood samples and other body fluids of patients with schizophrenia suggests a potential role as biomarkers, which might help disease subtyping, and the development of etiological treatments for immune dysregulation in schizophrenia.

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Data Availability

The data in this article were derived from the GEO (http://www.ncbi.nlm.nih.gov/geo/) and the Stanley Medical Research Institute (SMRI) Array Collection (http://www.stanleyresearch.org/brain-research/array-collection/), as described in the methods section and in the Supplementary information file.

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Acknowledgements

We thank Professor Eytan Domany for his help with the infrastructure that enabled the performance of this project.

Funding

The meta-analysis was partially funded by Marguerite Stolz Research Fellowship Fund for Junior Faculty in Medicine and Health Professions in Tel-Aviv University. The funders did not have any role in the performance of this meta-analysis.

Author information

Authors and Affiliations

  1. The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel

    Anat Shamir, Aviv Segev & Libi Hertzberg

  2. Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel

    Assif Yitzhaky & Libi Hertzberg

  3. Shalvata Mental Health Center, 13 Aliat Hanoar St, 45100, Hod Hasharon, Israel

    Aviv Segev & Libi Hertzberg

  4. Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Vahram Haroutunian & Pavel Katsel

  5. Department of Psychiatry (MIRECC), James J Peters VA Medical Center, Bronx, NY, USA

    Vahram Haroutunian

Authors
  1. Anat Shamir
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  2. Assif Yitzhaky
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  3. Aviv Segev
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  4. Vahram Haroutunian
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  5. Pavel Katsel
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  6. Libi Hertzberg
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Contributions

LH and AS designed and planned the project. AY performed the computational analysis. AS, AS, VH, PK, and LH interpreted the biological significance of the results. AS wrote the manuscript and LH and AS edited it.

Corresponding author

Correspondence to Libi Hertzberg.

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All Authors declare that there is no conflict of interest.

Ethical Approval

No Institutional Review Board approvals were required for this study, as all findings were derived from published datasets, as stated below under “Availability of data and materials.”

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No informed consent to participate statements were required for this study, as all findings were derived from datasets, as stated below under “Availability of data and materials.”

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No informed consent for publication statements were required for this study, as all findings were derived from datasets, as stated below under “Availability of data and materials.”

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Shamir, A., Yitzhaky, A., Segev, A. et al. Up-Regulation of S100 Gene Family in Brain Samples of a Subgroup of Individuals with Schizophrenia: Meta-analysis. Neuromol Med 25, 388–401 (2023). https://doi.org/10.1007/s12017-023-08743-4

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  • DOI: https://doi.org/10.1007/s12017-023-08743-4

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