ArticleFrontiers in immunology2020
Increased Macrophages and C1qA, C3, C4 Transcripts in the Midbrain of People With Schizophrenia.
Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 3 of them syntheses that pooled it.
What it found
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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.
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Who cites it
46 citing papers in PubMed, 3 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- The impact of sex on gene expression in the brain of schizophrenic patients: a systematic review and meta-analysis of transcriptomic studies.Biology of sex differences · 2024Pooled it
- Brain Inflammatory Marker Abnormalities in Major Psychiatric Diseases: a Systematic Review of Postmortem Brain Studies.Molecular neurobiology · 2023Pooled it
- Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives.Frontiers in psychiatry · 2022Pooled it
- Altered Vascular and Angiogenic Transcripts in the Neurogenic Niche in Neuroinflammatory-Type Schizophrenia.Schizophrenia bulletin · 2026Article
- TLR7 alters the maternal immune landscape during influenza A infection to increase maternal and fetal morbidity.Science advances · 2026Article
- Peripheral lncRNA-IL1RAP Dysregulation in Schizophrenia: A Multi-Omics Bridge Between Immunity and Diagnosis.Brain and behavior · 2026Article
- Increased Tumor Necrosis Factor Superfamily Members in Neuroinflammatory Schizophrenia and Bipolar Disorder Midbrains.Biological psychiatry global open science · 2026Article
- The Role of Amphiregulin and Epidermal Growth Factor Receptor in First-Episode Psychosis: Exploring Links to Schizophrenia Pathophysiology.Noro psikiyatri arsivi · 2026Article
- The tango of immune and neural cells: orchestrating neuroinflammation mediated brain disorders.Frontiers in immunology · 2026Review
- Molecular Evidence for Altered Angiogenesis in Neuroinflammation-Associated Schizophrenia and Bipolar Disorder Implicate an Abnormal Midbrain Blood-Brain Barrier.Schizophrenia bulletin · 2025Article
- The Role of Astrocytes in the Molecular Pathophysiology of Schizophrenia: Between Neurodevelopment and Neurodegeneration.Biomolecules · 2025Review
- Involvement of virus infections and antiviral agents in schizophrenia.Psychological medicine · 2025Review
- Article
- Blood-Brain Barrier Disruption in Schizophrenia: Insights, Mechanisms, and Future Directions.International journal of molecular sciences · 2025Review
- The role of the microbiota-gut-brain axis in schizophrenia: an immunological perspective.Frontiers in immunology · 2025Review
- Investigating the Relationship of Serum CD163, YKL40 and VILIP-1 Levels with Autism Severity and Language-cognitive Development in Preschool Children with Autism.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2024Article
- Bioenergetic and Inflammatory Alterations in Regressed and Non-Regressed Patients with Autism Spectrum Disorder.International journal of molecular sciences · 2024Article
- The potential role of the p75 receptor in schizophrenia: neuroimmunomodulation and making life or death decisions.Brain, behavior, & immunity - health · 2024Article
- Article
- Association study of the complement component C4 gene and suicide risk in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Increased cytokine and inflammatory-related transcripts are found in the ventral midbrain, a dopamine neuron-rich region associated with schizophrenia symptoms. In fact, half of schizophrenia cases can be defined as having a "high inflammatory/immune biotype." Recent studies implicate both complement and macrophages in cortical neuroinflammation in schizophrenia. Our aim was to determine whether measures of transcripts related to phagocytosis/macrophages (CD163, CD64, and FN1), or related to macrophage adhesion [intercellular adhesion molecule 1 (ICAM1)], or whether CD163+ cell density, as well as protein and/or gene expression of complement pathway activators (C1qA) and mediators (C3 or C4), are increased in the midbrain in schizophrenia, especially in those with a high inflammatory biotype. We investigated whether complement mRNA levels correlate with macrophage and/or microglia and/or astrocyte markers. We found CD163+ cells around blood vessels and in the parenchyma and increases in ICAM1, CD163, CD64, and FN1 mRNAs as well as increases in all complement transcripts in the midbrain of schizophrenia cases with high inflammation. While we found positive correlations between complement transcripts (C1qA and C3) and microglia or astrocyte markers across diagnostic and inflammatory subgroups, the only unique strong positive correlation was between CD163 and C1qA mRNAs in schizophrenia cases with high inflammation. Our study is the first to suggest that more circulating macrophages may be attracted to the midbrain in schizophrenia, and that increased macrophages are linked to increased complement pathway activation in tissue and may contribute to dopamine dysregulation in schizophrenia. Single-cell transcriptomic studies and mechanistic preclinical studies are required to test these possibilities.
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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.