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Blood‑brain barrier dysfunction in schizophrenia: Mechanisms and implications (Review)

  • Authors:
    • Shuang Lv
    • Chunxia Luo
  • View Affiliations / Copyright

    Affiliations: Department of Psychiatry, The Psychiatric Hospital of Guangzhou Civil Administration Bureau, Guangzhou, Guangdong 510430, P.R. China
    Copyright: © Lv et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 153
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    Published online on: July 22, 2025
       https://doi.org/10.3892/ijmm.2025.5594
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Abstract

The present review explored the emerging role of blood‑brain barrier (BBB) dysfunction in schizophrenia. Findings from biochemical markers, neuroimaging, genetic studies and experimental models are integrated to examine the impact of BBB dysfunction on the development and progression of schizophrenia. Additionally, the mechanisms by which BBB dysfunction exacerbates the schizophrenia were examined, including disruptions in cerebral blood flow, the facilitation of neuroinflammation and alterations in neurotransmitter systems. Finally, the potential for integrating BBB‑targeted interventions into broader therapeutic strategies for schizophrenia were discussed, with the goal of improving drug efficacy and minimizing side effects in clinical practice.
View Figures

Figure 1

BBB structure. The BBB is composed of
endothelial cells that form the vessel wall and are surrounded by
astrocyte end-foot processes and embedded pericytes. These
endothelial cells contain P-glycoproteins and mitochondria, which
regulate metabolic processes and substances entering the brain. The
central lumen contains blood flow. Endothelial tight junctions are
formed of components such as JAM proteins, occludin and claudins.
ZO proteins and the actin vinculin-based cytoskeleton provide
structural support. BBB, blood-brain barrier; JAM, junctional
adhesion molecules; ZO, zona occludens.

Figure 2

Mechanisms linking BBB breakdown to
schizophrenia. The disruption of the BBB in schizophrenia serves a
key role in disease progression through several mechanisms: i)
Impairment of cerebral blood flow, which limits nutrient and oxygen
delivery to brain tissue; ii) facilitation of neuroinflammation,
where BBB breakdown allows peripheral immune cells and inflammatory
cytokines to enter the central nervous system; and iii) alteration
of neurotransmitter systems, including NMDAR autoantibody and
dysregulation in neurotransmitter synthesis. BBB, blood-brain
barrier; NMDAR, N-methyl-D-aspartate receptor.
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Copy and paste a formatted citation
Spandidos Publications style
Lv S and Luo C: Blood‑brain barrier dysfunction in schizophrenia: Mechanisms and implications (Review). Int J Mol Med 56: 153, 2025.
APA
Lv, S., & Luo, C. (2025). Blood‑brain barrier dysfunction in schizophrenia: Mechanisms and implications (Review). International Journal of Molecular Medicine, 56, 153. https://doi.org/10.3892/ijmm.2025.5594
MLA
Lv, S., Luo, C."Blood‑brain barrier dysfunction in schizophrenia: Mechanisms and implications (Review)". International Journal of Molecular Medicine 56.4 (2025): 153.
Chicago
Lv, S., Luo, C."Blood‑brain barrier dysfunction in schizophrenia: Mechanisms and implications (Review)". International Journal of Molecular Medicine 56, no. 4 (2025): 153. https://doi.org/10.3892/ijmm.2025.5594
Copy and paste a formatted citation
x
Spandidos Publications style
Lv S and Luo C: Blood‑brain barrier dysfunction in schizophrenia: Mechanisms and implications (Review). Int J Mol Med 56: 153, 2025.
APA
Lv, S., & Luo, C. (2025). Blood‑brain barrier dysfunction in schizophrenia: Mechanisms and implications (Review). International Journal of Molecular Medicine, 56, 153. https://doi.org/10.3892/ijmm.2025.5594
MLA
Lv, S., Luo, C."Blood‑brain barrier dysfunction in schizophrenia: Mechanisms and implications (Review)". International Journal of Molecular Medicine 56.4 (2025): 153.
Chicago
Lv, S., Luo, C."Blood‑brain barrier dysfunction in schizophrenia: Mechanisms and implications (Review)". International Journal of Molecular Medicine 56, no. 4 (2025): 153. https://doi.org/10.3892/ijmm.2025.5594
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