ArticleMolecular psychiatry2018
Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 2 of them syntheses that pooled it.
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Who cites it
134 citing papers in PubMed, 2 syntheses or guidelines pooled it, 238 citations in OpenAlex.
- Convergent blood-brain barrier breakdown in schizophrenia and autism spectrum disorders: a systematic review of preclinical animal models.Fluids and barriers of the CNS · 2026Pooled it
- Zonulin-Dependent Intestinal Permeability in Children Diagnosed with Mental Disorders: A Systematic Review and Meta-Analysis.Nutrients · 2020Pooled it
- Developmental Brain Network Trajectories Differentiate Resilience and Vulnerability to Psychosis in 22q11.2 Deletion Syndrome.Biological psychiatry global open science · 2026Article
- Altered Vascular and Angiogenic Transcripts in the Neurogenic Niche in Neuroinflammatory-Type Schizophrenia.Schizophrenia bulletin · 2026Article
- Vascular Endothelial Barrier in Salivary Glands: From Physiological Regulation to Pathological Impairment of Secretion.International journal of molecular sciences · 2026Review
- Comprehensive analysis of interactions between brain aging and late-onset psychoses using heuristic mapping models.Communications medicine · 2026Article
- Dysregulation of neurovascular unit in the retina after optic nerve injury.BMC ophthalmology · 2026Article
- Investigation of Tight Junction Protein Alterations in ADHD: The Role of Claudin-5, β-Catenin and Paxillin.Journal of attention disorders · 2026Article
- Cerebrovascular claudin-5 isoform expression correlates with worsened stroke outcomes following thromboembolic stroke.Fluids and barriers of the CNS · 2026Article
- EHD4 and ASAP2 are critical negative regulators of the claudin-5-based endothelial barrier.The FEBS journal · 2026Article
- Trauma exposure, PTSD, and methylation of the blood brain barrier claudin-5 gene.Psychoneuroendocrinology · 2026Article
- The role of tight junction proteins in the pathogenesis of schizophrenia.European archives of psychiatry and clinical neuroscience · 2026Review
- The stroke risk gene Foxf2 maintains brain endothelial cell function via Tie2 signaling.Nature neuroscience · 2026Article
- Investigation of <italic>CLDN5</italic> Gene 3' Untranslated Region rs10314 Polymorphism and Protein Levels in Children and Adolescents with Attention-Deficit Hyperactivity Disorder: A Molecular and Clinical Correlation Study.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2026Article
- Krüppel-Like Factors Modulate Susceptibility To Neuropsychiatric Disorders.Molecular neurobiology · 2025Review
- Chronic Stress and Astrocyte Dysfunction in Depression: Molecular Mechanisms and Gene Expression Changes.Antioxidants (Basel, Switzerland) · 2025Review
- Dynamic Inner Blood Retina Barrier Disruption in Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2025Article
- Reviewing vascular influences on neuronal migration, cortical development, and neurodevelopmental disorders: focus on autism, ADHD and schizophrenia.Molecular psychiatry · 2025Review
- Early-life gut microbiome maturity regulates blood-brain barrier and cognitive development.Gut microbes · 2025Article
- Trauma Exposure, PTSD, and Methylation of the Blood Brain Barrier Claudin-5 Gene.medRxiv : the preprint server for health sciences · 2025Article
74 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 9 institutions in 3 countries.
Funding
Abstract
Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells. We also show that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized BBB disruption and behavioural changes. Using an inducible 'knockdown' mouse model, we further link claudin-5 suppression with psychosis through a distinct behavioural phenotype showing impairments in learning and memory, anxiety-like behaviour and sensorimotor gating. In addition, these animals develop seizures and die after 3-4 weeks of claudin-5 suppression, reinforcing the crucial role of claudin-5 in normal neurological function. Finally, we show that anti-psychotic medications dose-dependently increase claudin-5 expression in vitro and in vivo while aberrant, discontinuous expression of claudin-5 in the brains of schizophrenic patients post mortem was observed compared to age-matched controls. Together, these data suggest that BBB disruption may be a modifying factor in the development of schizophrenia and that drugs directly targeting the BBB may offer new therapeutic opportunities for treating this disorder.
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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.