Evidence map›Paper›PMID 39471484›Full record

ArticleSchizophrenia bulletin2025

Molecular Evidence for Altered Angiogenesis in Neuroinflammation-Associated Schizophrenia and Bipolar Disorder Implicate an Abnormal Midbrain Blood-Brain Barrier.

Yunting Zhu, Maree J Webster, Gerardo Mendez Victoriano, Frank A Middleton, Paul T Massa, Cynthia Shannon Weickert

Abstract read
In one paragraph

Article in Schizophrenia bulletin, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Short-Term Impacts of PMGeoHealth · 2026
    Article
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  6. Article
  7. Review
  8. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Yunting ZhuDepartment of Neuroscience and Physiology, Upstate Medical University, Syracuse, NY 13210, United States.ORCID 0000-0002-2072-209X
Maree J WebsterStanley Medical Research Institute, 9800 Medical Center Drive, Rockville, MD, United States.
Gerardo Mendez VictorianoSchizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW 2031, Australia.
Frank A MiddletonDepartment of Neuroscience and Physiology, Upstate Medical University, Syracuse, NY 13210, United States.
Paul T MassaDepartment of Neurology, Upstate Medical University, Syracuse, NY 13210, United States.
Cynthia Shannon WeickertDepartment of Neuroscience and Physiology, Upstate Medical University, Syracuse, NY 13210, United States.

Funding

National Health and Medical Research Council 2009237The NSW Ministry of Health, Office of Health and Medical Research
6 · The paper itself

Abstract

background and hypothesisAngiogenesis triggered by inflammation increases BBB permeability and facilitates macrophage transmigration. In the midbrain, we have discovered molecular alterations related to the blood-brain barrier (BBB), including endothelial cell changes associated with macrophage diapedesis, in neuroinflammatory schizophrenia and bipolar disorder, but changes in angiogenesis are yet to be reported. Hypothesis: We expected to discover molecular evidence of altered angiogenesis in the midbrain in individuals with schizophrenia and bipolar disorder compared to controls, with these changes more evident in "high" inflammation schizophrenia as compared to "low" inflammation. STUDY

designIn a case-control post-mortem cohort including schizophrenia (n = 35), bipolar disorder (n = 35), and controls (n = 33), we measured mRNA (RT-PCR) and protein (multiplex immunoassays) and performed immunohistochemistry to determine levels and anatomical distribution of angiogenesis-related molecules in the ventral midbrain. STUDY

resultsWe found large changes in angiogenesis factors in bipolar disorder high inflammatory subgroup (increased angiopoietin-2 and SERPINE1 mRNAs, but decreased angiopoietin-1, angiopoietin-2, and TEK receptor proteins). In schizophrenia high inflammatory subgroup, we found a robust increase in SERPINE1 mRNA and protein levels. However, we found no significant changes in angiopoietins in schizophrenia. We found that VEGFA mRNA level was increased in high inflammation schizophrenia, but only reached statistical significance compared to one low inflammatory subgroup.

conclusionsThus, angiogenesis signaling pathways appeared to be involved in the BBB alterations when inflammation is also present in the midbrain of schizophrenia and bipolar disorder, with increased levels of SERPINE1 in schizophrenia high inflammatory subgroup and with a putative suppression of angiopoietin signaling in bipolar disorder high inflammatory subgroup.

Indexed as

Bipolar DisorderBlood-Brain BarrierInflammationMesencephalonNeovascularization, PathologicNeuroinflammatory DiseasesSchizophreniaAdultAgedAngiogenesisAngiopoietin-1Angiopoietin-2Case-Control StudiesFemaleHumansMaleAngiopoietin-1Angiopoietin-2ANGPT1 protein, humanANGPT2 protein, humanPlasminogen Activator Inhibitor 1SERPINE1 protein, humanVascular Endothelial Growth Factor Aangiogenesisangiopoietinbipolar disorderblood-brain barrierinflammationschizophrenia

Identifiers

PMID39471484
PMCPMC12236309

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Registered trials

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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.