<i>GRIA</i> Gene Expression in Schizophrenia: A Participant-Level Meta-Analysis.

Overview

1. School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, 6997801 Tel Aviv, Israel
2. Department of Physics of Complex Systems, Weizmann Institute of Science, 7610001 Rehovot, Israel
3. Adult Inpatient Ward, Shalvata Mental Health Center, 45100 Hod Hasharon, Israel

Abstract

Background: Schizophrenia is a complex mental disorder with an estimated heritability of 80%, yet its underlying pathophysiology remains poorly understood. Emerging evidence implicates the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor—a key player in fast excitatory synaptic transmission, encoded by Glutamate Ionotropic Receptor AMPA Type Subunits 1-4 (GRIA1-4)—in the disorder's pathophysiology. However, findings from postmortem brain samples regarding GRIA1-4 expression have been inconsistent. This study aimed to systematically evaluate the differential expression of GRIA1-4 genes in schizophrenia by integrating transcriptomic data from postmortem brain tissue and patient-derived cerebral organoids.

Methods: We conducted a participant-level meta-analysis of seven postmortem brain sample datasets (n = 295; 151 schizophrenia, 144 controls) and analyzed an independent organoid dataset (n = 16). Expression differences between schizophrenia and control samples were quantified using Hedges' g under a random-effects model, with heterogeneity assessed using the I2 statistic.

Results: Our analysis revealed significant downregulation of all four GRIA genes (GRIA1-4) in postmortem brain tissue from individuals with schizophrenia, with the effect concentrated in a subgroup of patients. No substantial heterogeneity was attributable to differences in brain regions or measurement platforms. Consistent downregulation of GRIA1-3 was observed in patient-derived cerebral organoids, which model early neurodevelopmental stages.

Conclusions: Our findings highlight AMPA receptor dysfunction as a potential contributor to schizophrenia pathophysiology in a subgroup of patients, consistent with the broader role of glutamatergic signaling disruption in this disorder. The convergent evidence from postmortem brain tissue and developmental models underscores the need for further investigation of GRIA genes as potential biomarkers for patient stratification and as therapeutic targets. While further study is needed to understand the functional consequences of our findings, such insights may inform the development of personalized treatment strategies targeting glutamatergic dysfunction in schizophrenia.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Data links

• ncbi.nlm.nih.gov/geo, NCBI; found in “Availability of Data and Materials”

Availability of Data and Materials

All datasets analyzed in this study were previously published and are publicly accessible through the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 6 keywords, 83 references.

Cite

This paper

Baumel, A., Yitzhaky, A., & Hertzberg, L. (2026). <i>GRIA</i> Gene Expression in Schizophrenia: A Participant-Level Meta-Analysis. Alpha psychiatry, 27(3), 46200. https://doi.org/10.31083/ap46200

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1038/s41386-026-02406-1 [code]

Functional genomic profiling of schizophrenia-associated genes reveals key microglial regulators.

Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

In common: schizophrenia / psychosis, genetics / omics, cellular / molecular, 4 references

[2] doi:10.1126/sciadv.aea0755

Schizophrenia risk gene ZNF804A controls ribosome localization and synaptogenesis in developing human neurons.

Journal: Science advances

In common: schizophrenia / psychosis, genetics / omics, cellular / molecular, 4 references

[3] doi:10.1038/s41588-026-02646-3 [code]

Co-expression-based models improve eQTL predictions for transcriptome-wide association studies and highlight new schizophrenia-associated genes.

Journal: Nature genetics

In common: schizophrenia / psychosis, genetics / omics, cellular / molecular, 4 references

[4] doi:10.3390/nu18172887

Unmetabolized Folic Acid: Biology, Epidemiology, and Clinical Consequences: A Systematic Review.

Journal: Nutrients

In common: 4 references

[5] doi:10.1038/s41380-026-03587-3

Loss of schizophrenia risk gene XPO7 disrupts neuronal excitability and network regularity via altered Na<sup>+</sup> channel dynamics in human neurons.

Journal: Molecular psychiatry

In common: schizophrenia / psychosis, genetics / omics, cellular / molecular, 3 references

[6] doi:10.1038/s41380-026-03574-8

Genome-wide tandem repeat expansions modify schizophrenia risk in the presence of a 22q11.2 deletion.

Journal: Molecular psychiatry

In common: schizophrenia / psychosis, genetics / omics, 3 references

[7] doi:10.1038/s41467-026-71542-5 [code]

Astrocyte fatty acid metabolism as a driver of risk for major depressive disorder.

Journal: Nature communications

In common: genetics / omics, cellular / molecular, 3 references

[8] doi:10.1186/s13041-026-01300-7

Hippocampal transcriptome profiling in a 22q11.2 deletion syndrome mouse model: comparison with human schizophrenia.

Journal: Molecular brain

In common: schizophrenia / psychosis, genetics / omics, cellular / molecular, 2 references

[9] doi:10.3389/fnmol.2026.1844705 [code]

Risperidone regulates the expression of schizophrenia-related genes in the forebrain of adult male mice.

Journal: Frontiers in molecular neuroscience

In common: schizophrenia / psychosis, genetics / omics, cellular / molecular, 2 references

[10] doi:10.3389/fnagi.2026.1806505 [code]

ALDH1A1-dopaminergic gene co-expression in human substantia nigra: meta-analysis of disease-associated correlation changes across seven independent Parkinson's disease datasets.

Journal: Frontiers in aging neuroscience

In common: cellular / molecular, 3 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.