ArticleMolecular psychiatry2026
Extracellular matrix dysfunction and synaptic alterations in schizophrenia.
Article in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- Proteomic health archetypes identified in disease-free adults enable risk assessment for diverse chronic diseases.Genome medicine · 2026Article
- The extracellular matrix as a dynamic regulator of brain function and plasticity.Neurobiology of disease · 2026Review
- Human-Derived Cellular Models in Psychiatry: A Focus on the Olfactory Neuroepithelium.Brain sciences · 2026Review
- Whole-Exome Sequencing Identifies Novel Genetic Variants Associated with Unexplained Neurodevelopmental Disorders in Children.International journal of molecular sciences · 2026Article
- Olfactory models as a platform for neuroscience research.Frontiers in cellular neuroscience · 2026Review
- MiR-7 in neurological disorders: beyond metabolic dysregulation.Frontiers in neuroscience · 2026Review
- The Etiological Role of Impaired Neurogenesis in Schizophrenia: Interactions with Inflammatory, Microbiome and Hormonal Signaling.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Schizophrenia is a complex disorder with strong evidence implicating neurodevelopmental abnormalities in its pathophysiology. Olfactory neuroepithelial cells from patients provide a unique platform for studying neurodevelopmental processes. These cells can be cultured into neurospheres and differentiated into neurons, allowing the study of patient-specific alterations related to the disorder. In this study, we utilized olfactory neuroepithelial cells from patients with schizophrenia and controls to explore putative neurodevelopmental dysregulations. RNA-sequencing of neurospheres transcriptome revealed significant alterations in extracellular matrix-related gene expression, suggesting extracellular matrix dysregulation as an underlying contributor to schizophrenia etiopathogenesis. Upon differentiation of olfactory neuroepithelial cells into neurons, transcriptomic analysis identified a significant downregulation of genes involved in synaptic organization and extracellular matrix interactions. To validate these findings, we quantified the protein levels of these genes in olfactory neuroepithelium-derived neurons and in postmortem dorsolateral prefrontal cortex tissue from schizophrenia patients and matched controls. Consistent with our transcriptomic data, schizophrenia subjects exhibited decreased levels of L1CAM, SCG2, and NPTXR proteins. Furthermore, we identified a correlation between the protein levels of L1CAM and NPTXR in the brains of individuals with schizophrenia, a relationship that was absent in control subjects. Our findings provide robust evidence for extracellular matrix and synaptic dysregulation in schizophrenia, linking neurodevelopmental disruptions to molecular alterations in both patient-derived cellular models and postmortem brain. These results underscore the utility of olfactory neuroepithelium cells as a model for studying the neurodevelopmental basis of schizophrenia. They also highlight extracellular matrix-related pathways as potential targets for future search of biomarkers and therapeutic development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.