ArticleMolecular psychiatry2022
Schizophrenia-derived hiPSC brain microvascular endothelial-like cells show impairments in angiogenesis and blood-brain barrier function.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Altered Vascular and Angiogenic Transcripts in the Neurogenic Niche in Neuroinflammatory-Type Schizophrenia.Schizophrenia bulletin · 2026Article
- Nitric Oxide-S-Nitrosylation and Its Role in Neuroinflammation Associated with Neuropsychiatric Conditions.International journal of molecular sciences · 2026Review
- The Eph-ephrin system in neuropsychiatric and neurodevelopmental disorders.Journal of psychiatry & neuroscience : JPN · 2026Review
- Patient-derived stem cell models of brain endothelial-neuron interactions in early course psychosis.Frontiers in psychiatry · 2026Article
- The intersection of circadian rhythms and the blood-brain barrier with drug efficacy and delivery in neurological disorders.Advanced drug delivery reviews · 2025Review
- Association between endogenous lactate accumulation and dysregulated activation of the NLRP3 inflammasome pathway in schizophrenia.Scientific reports · 2025Observational
- A Systematic Review and Meta-Analysis of Arterial Spin Labeling Magnetic Resonance Imaging Studies in Psychosis Spectrum Disorders.Noro psikiyatri arsivi · 2025Review
- Integrative metabolomics-genomics analysis identifies key networks in a stem cell-based model of schizophrenia.Molecular psychiatry · 2024Article
- Saxitoxin potentiates human neuronal cell death induced by Zika virus while sparing neural progenitors and astrocytes.Scientific reports · 2024Article
- Multimorbidity in Severe Mental Illness as Part of the Neurodevelopmental Continuum: Physical Health-Related Endophenotypes of Schizophrenia-A Narrative Review.Brain sciences · 2024Review
- A network of transcriptomic signatures identifies novel comorbidity mechanisms between schizophrenia and somatic disorders.Discover mental health · 2024Article
- Schizophrenia endothelial cells exhibit higher permeability and altered angiogenesis patterns in patient-derived organoids.Translational psychiatry · 2024Article
- Article
- Involvement of an Aberrant Vascular System in Neurodevelopmental, Neuropsychiatric, and Neuro-Degenerative Diseases.Life (Basel, Switzerland) · 2023Review
- Formulating treatment of major psychiatric disorders: algorithm targets the dominantly affected brain cell-types.Discover mental health · 2023Review
- Single-nucleus RNA sequencing of midbrain blood-brain barrier cells in schizophrenia reveals subtle transcriptional changes with overall preservation of cellular proportions and phenotypes.Molecular psychiatry · 2022Article
- Article
- It takes two to tango: Widening our understanding of the onset of schizophrenia from a neuro-angiogenic perspective.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Schizophrenia (SZ) is a complex neuropsychiatric disorder, affecting 1% of the world population. Long-standing clinical observations and molecular data have pointed to a possible vascular deficiency that could be acting synergistically with neuronal dysfunction in SZ. As SZ is a neurodevelopmental disease, the use of human-induced pluripotent stem cells (hiPSC) allows disease biology modeling while retaining the patient's unique genetic signature. Previously, we reported a VEGFA signaling impairment in SZ-hiPSC-derived neural lineages leading to decreased angiogenesis. Here, we present a functional characterization of SZ-derived brain microvascular endothelial-like cells (BEC), the counterpart of the neurovascular crosstalk, revealing an intrinsically defective blood-brain barrier (BBB) phenotype. Transcriptomic assessment of genes related to endothelial function among three control (Ctrl BEC) and five schizophrenia patients derived BEC (SZP BEC), revealed that SZP BEC have a distinctive expression pattern of angiogenic and BBB-associated genes. Functionally, SZP BEC showed a decreased angiogenic response in vitro and higher transpermeability than Ctrl BEC. Immunofluorescence staining revealed less expression and altered distribution of tight junction proteins in SZP BEC. Moreover, SZP BEC's conditioned media reduced barrier capacities in the brain microvascular endothelial cell line HCMEC/D3 and in an in vivo permeability assay in mice. Overall, our results describe an intrinsic failure of SZP BEC for proper barrier function. These findings are consistent with the hypothesis tracing schizophrenia origins to brain development and BBB dysfunction.
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