Inflammation-related genes up-regulated in schizophrenia brains

BackgroundMultiple studies have shown that brain gene expression is disturbed in subjects suffering from schizophrenia. However, disentangling disease effects from alterations caused by medication is a challenging task. The main goal of this study is to find transcriptional alterations in schizophrenia that are independent of neuroleptic treatment.MethodsWe compared the transcriptional profiles in brain autopsy samples from 55 control individuals with that from 55 schizophrenic subjects, subdivided according to the type of antipsychotic medication received.ResultsUsing global and high-resolution mRNA quantification techniques, we show that genes involved in immune response (GO:0006955) are up regulated in all groups of patients, including those not treated at the time of death. In particular, IFITM2, IFITM3, SERPINA3, and GBP1 showed increased mRNA levels in schizophrenia (p-values from qPCR ≤ 0.01). These four genes were co-expressed in both schizophrenic subjects and controls. In-vitro experiments suggest that these genes are expressed in both oligodendrocyte and endothelial cells, where transcription is inducible by the inflammatory cytokines TNF-α, IFN-α and IFN-γ.ConclusionAlthough the modified genes are not classical indicators of chronic or acute inflammation, our results indicate alterations of inflammation-related pathways in schizophrenia. In addition, the observation in oligodendrocyte cells suggests that alterations in inflammatory-related genes may have consequences for myelination. Our findings encourage future research to explore whether anti-inflammatory agents can be used in combination with traditional antipsychotics for a more efficient treatment of schizophrenia.

• Publication year

  2007

• Venue

  BMC Psychiatry

• Publication date

  2007-09-06

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/1471-244X-7-46PMID 17822540PMCID 2080573
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The injury response of oligodendrocyte precursor cells is induced by platelets, macrophages and inflammation-associated cytokines.

  2006cited by this paper
• Myelin-associated mRNA and protein expression deficits in the anterior cingulate cortex and hippocampus in elderly schizophrenia patients.

  2006cited by this paper
• RNA metabolism and dysmyelination in schizophrenia.

  2006cited by this paper
• Critical appraisal of DNA microarrays in psychiatric genomics.

  2006cited by this paper
• Human QKI, a new candidate gene for schizophrenia involved in myelination

  2006cited by this paper
• Human QKI, a potential regulator of mRNA expression of human oligodendrocyte-related genes involved in schizophrenia.

  2006influential reference
• Prenatal and postnatal maternal contributions in the infection model of schizophrenia

  2006cited by this paper
• Inflammation stimulates myelination by transplanted oligodendrocyte precursor cells

  2006cited by this paper
• See no evil, hear no evil, do no evil: the lessons of immune privilege

  2006cited by this paper
• Review: The Guanylate-Binding Proteins (GBPs): Proinflammatory Cytokine-Induced Members of the Dynamin Superfamily with Unique GTPase Activity

  2005cited by this paper
• Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

  2005influential reference
• The Murine Orthologue of Human Antichymotrypsin

  2005cited by this paper
• THE MURINE ORTHOLOGUE OF HUMAN ANTICHYMOTRYPSIN: A STRUCTURAL PARADIGM FOR CLADE A3 SERPINS

  2005cited by this paper
• Impact of haloperidol and risperidone on gene expression profile in the rat cortex.

  2005cited by this paper
• IFITM/Mil/fragilis family proteins IFITM1 and IFITM3 play distinct roles in mouse primordial germ cell homing and repulsion.

  2005cited by this paper
• Statistical modeling in case-control real-time RT-PCR assays, for identification of differentially expressed genes in schizophrenia.

  2005cited by this paper
• Human guanylate binding protein-1 (hGBP-1) characterizes and establishes a non-angiogenic endothelial cell activation phenotype in inflammatory diseases.

  2005cited by this paper
• GOstat: find statistically overrepresented Gene Ontologies within a group of genes.

  2004cited by this paper
• Prefrontal Abnormality of Schizophrenia Revealed by DNA Microarray: Impact on Glial and Neurotrophic Gene Expression

  2004cited by this paper
• Perinatal inflammatory cytokine challenge results in distinct neurobehavioral alterations in rats: implication in psychiatric disorders of developmental origin.

  2004cited by this paper
• Microarray analysis of postmortem temporal cortex from patients with schizophrenia

  2004cited by this paper
• Improvement in negative symptoms of schizophrenia with antibodies to tumor necrosis factor-alpha and to interferon-gamma: a case report.

  2003cited by this paper
• Season of birth and inflammatory response system in schizophrenia.

  2003cited by this paper
• Inflammatory disorders of the central nervous system.

  2003cited by this paper
• Oligodendrocyte dysfunction in schizophrenia and bipolar disorder.

  2003cited by this paper
• Induction of tubulogenesis in telomerase-immortalized human microvascular endothelial cells by glioblastoma cells.

  2002cited by this paper
• Maternal infection: window on neuroimmune interactions in fetal brain development and mental illness.

  2002cited by this paper
• Guanylate-binding protein-1 expression is selectively induced by inflammatory cytokines and is an activation marker of endothelial cells during inflammatory diseases.

  2002cited by this paper
• Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia

  2001cited by this paper
• Review of immunological and immunopathological findings in schizophrenia.

  2001cited by this paper
• High-resolution quantification of specific mRNA levels in human brain autopsies and biopsies.

  2000cited by this paper
• Alternative splicing prevents transferrin secretion during differentiation of a human oligodendrocyte cell line

  2000influential reference
• The neuropathology of schizophrenia. A critical review of the data and their interpretation.

  1999cited by this paper
• Seasonality and infectious disease in schizophrenia: the birth hypothesis revisited.

  1999cited by this paper
• The inflammatory response system in treatment-resistant schizophrenia: increased serum interleukin-6.

  1998cited by this paper
• Nonsteroidal Anti-Inflammatory Drugs and Severe Psychiatric Side Effects

  1996cited by this paper
• Treatment of schizophrenic disorder, paranoid type, with intramuscular recombinant alpha-2b interferon.

  1993cited by this paper
• Schizophrenia following pre-natal exposure to influenza epidemics between 1939 and 1960.

  1992cited by this paper
• [37] α1-antitrypsin

  1988cited by this paper
• Protease inhibitors of human plasma. Alpha 1-antitrypsin.

  1985cited by this paper
• Neuropathology of schizophrenia.

  1982cited by this paper
• Proteinase Inhibitors of Human Plasma

  1971cited by this paper

• Discovery of novel blood-brain barrier neuropathology in schizophrenia and bipolar disorder midbrain.

  2026cites this paper
• Effects of Exercise on Behavior and Hippocampal Neuroinflammation in Rat Model of Autism Spectrum Disorder

  2026cites this paper
• Metabolic shifts, a consequence of hyperosmolarity, are a hallmark of mental disorders.

  2026cites this paper
• Psychiatric Implications of Genetic Variations in Oligodendrocytes: Insights from hiPSC Models

  2025cites this paper
• Therapeutic modulation of unfolded protein response by biochemic tissue salts in alcohol- and acetaminophen-induced liver cirrhosis

  2025cites this paper
• Small for gestational age children at risk: Identifying placenta-brain axis genes as biomarkers for early prediction of neurodevelopmental delay.

  2025cites this paper
• Functional Genomic Profiling of Schizophrenia-Associated Genes Reveals Key Microglial Regulators

  2025cites this paper
• Canonical and non-canonical roles of oligodendrocyte precursor cells in mental disorders

  2025cites this paper
• Synaptic Pruning in Schizophrenia: Manifestations and Antecedents

  2025cites this paper
• Aging in Schizophrenia: Perspectives on Molecular Mechanisms and a Mini-review.

  2025cites this paper
• Acute systemic immune challenge induces cognitive impairments and anhedonia through interferon-induced transmembrane protein 3 in adult male mice.

  2025cites this paper
• Comparative Analysis of Serum BAFF and IL-17 Levels Pre- and Post-Antipsychotic Treatment for Acute Schizophrenia

  2025cites this paper
• Research Progress into the Biological Functions of IFITM3

  2024cites this paper
• Schizophrenia endothelial cells exhibit higher permeability and altered angiogenesis patterns in patient-derived organoids

  2024cites this paper
• Molecular Evidence for Altered Angiogenesis in Neuroinflammation-Associated Schizophrenia and Bipolar Disorder Implicate an Abnormal Midbrain Blood-Brain Barrier.

  2024cites this paper
• Changes in IL-6, IL-12, IL-5, IL-10 and TGF-β1 Concentration in Patients with Treatment-Resistant Schizophrenia (TRS) Following Electroconvulsive Therapy (ECT)—A Pilot Study

  2024cites this paper
• A Systematic Review on the Potential of Aspirin to Reduce Cardiovascular Risk in Schizophrenia

  2023cites this paper
• Brain microvascular endothelial cells and blood-brain barrier dysfunction in psychotic disorders

  2023cites this paper
• Brain Inflammatory Marker Abnormalities in Major Psychiatric Diseases: a Systematic Review of Postmortem Brain Studies

  2023cites this paper
• Increased prefrontal cortical cells positive for macrophage/microglial marker CD163 along blood vessels characterizes a neuropathology of neuroinflammatory schizophrenia.

  2023cites this paper
• The Relationship between Oral Health and Schizophrenia in Advanced Age—A Narrative Review in the Context of the Current Literature

  2023cites this paper
• The neuroimmune changes captured by transcriptome in brains of psychiatric and neurological disorders

  2022cites this paper
• Distinct Phenotypes of Inflammation Associated Macrophages and Microglia in the Prefrontal Cortex Schizophrenia Compared to Controls

  2022cites this paper
• Quetiapine Ameliorates MIA-Induced Impairment of Sensorimotor Gating: Focus on Neuron-Microglia Communication and the Inflammatory Response in the Frontal Cortex of Adult Offspring of Wistar Rats

  2022cites this paper
• Identification and analysis of circRNAs in the prefrontal cortices of wild boar and domestic pig

  2022cites this paper
• Altered purinergic receptor expression in the frontal cortex in schizophrenia

  2022cites this paper
• Cytokines as Potential Biomarkers of Clinical Characteristics of Schizophrenia

  2022influential citation
• Sex Differences in Neurodevelopmental Disorders: A Key Role for the Immune System.

  2022cites this paper
• Neuroimmune transcriptome changes in patient brains of psychiatric and neurological disorders

  2022cites this paper
• Amplitudes of resting-state functional networks – investigation into their correlates and biophysical properties

  2022cites this paper
• Inflammatory monocyte gene signature predicts beneficial within group effect of simvastatin in patients with schizophrenia spectrum disorders in a secondary analysis of a randomized controlled trial

  2022cites this paper
• Induced pluripotent stem cell-derived astrocytes from patients with schizophrenia exhibit an inflammatory phenotype that affects vascularization

  2022cites this paper
• Immune-Related Genomic Schizophrenic Subtyping Identified in DLPFC Transcriptome

  2022cites this paper
• Peripheral NF-κB dysregulation in people with schizophrenia drives inflammation: putative anti-inflammatory functions of NF-κB kinases

  2022cites this paper
• Composite immune marker scores associated with severe mental disorders and illness course

  2022cites this paper
• Psycho-immunologie

  2022cites this paper
• Neuroinflammation in schizophrenia: the role of nuclear factor kappa B

  2021cites this paper
• [Oxidative stress in schizophrenia as a promising target for psychopharmacotherapy].

  2021cites this paper
• Schizophrenia is defined by cell-specific neuropathology and multiple neurodevelopmental mechanisms in patient-derived cerebral organoids

  2021cites this paper
• Transcriptome Analysis of Post-Mortem Brain Tissue Reveals Up-Regulation of the Complement Cascade in a Subgroup of Schizophrenia Patients

  2021cites this paper
• Transcriptomic Data Analysis Reveals a Down-Expression of Galectin-8 in Schizophrenia Hippocampus

  2021cites this paper
• Serum proteomics reveals disorder of lipoprotein metabolism in sepsis

  2021cites this paper
• Core genes involved in the regulation of acute lung injury and their association with COVID-19 and tumor progression: A bioinformatics and experimental study

  2021cites this paper
• The emerging tale of microglia in psychiatric disorders.

  2021cites this paper
• Brain-immune interactions in neuropsychiatric disorders: lessons from transcriptome studies for molecular targeting.

  2021cites this paper
• Polymorphic SERPINA3 prolongs oligomeric state of amyloid beta

  2021cites this paper
• Metabolic Shifts as the Hallmark of Most Common Diseases: The Quest for the Underlying Unity

  2021cites this paper
• Concordance of Immune-Related Markers in Lymphocytes and Prefrontal Cortex in Schizophrenia

  2021cites this paper
• BRN2 and PTN unveil multiple neurodevelopmental mechanisms in Schizophrenia patient-derived cerebral organoids

  2021cites this paper
• Involvement of the nuclear factor-κB transcriptional complex in prefrontal cortex immune activation in bipolar disorder

  2021cites this paper
• Decreased serum apolipoprotein A4 as a potential peripheral biomarker for patients with schizophrenia.

  2021cites this paper
• IL-17A Contributes to the Angiotensin II-induced Neurovascular Coupling impairment through Oxidative Stress

  2021cites this paper
• Association between schizophrenia and periodontal disease in relation to cortisol levels: an ELISA-based descriptive analysis

  2021cites this paper
• A schizophrenia subgroup with elevated inflammation displays reduced microglia, increased peripheral immune cell and altered neurogenesis marker gene expression in the subependymal zone

  2021cites this paper
• Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment

  2021cites this paper
• The Effects of Paracetamol on the Liver and Kidney Functions of a Rat Model Following Prolonged Alcohol Administration

  2021cites this paper
• Dystrophy of Oligodendrocytes and Adjacent Microglia in Prefrontal Gray Matter in Schizophrenia

  2020cites this paper
• Perinatal Psychiatry: Ready for Prime Time?

  2020cites this paper
• Regional, cellular and species difference of two key neuroinflammatory genes implicated in schizophrenia.

  2020cites this paper
• Prenatal exposure to environmental insults and enhanced risk of developing Schizophrenia and Autism Spectrum Disorder: focus on biological pathways and epigenetic mechanisms.

  2020cites this paper
• O papel do sistema imune na neurogênese da esquizofrenia com enfoque na neuroinflamação/ The role of the immune system in the neurogenesis of schizophrenia with a focus on neuroinflammation

  2020cites this paper
• Key role for lipids in cognitive symptoms of schizophrenia

  2020cites this paper
• C-Reactive Protein/Albumin and Neutrophil/Albumin Ratios as Novel Inflammatory Markers in Patients with Schizophrenia

  2020cites this paper
• Integrating genome-wide association study and methylation functional annotation data identified candidate genes and pathways for schizophrenia.

  2020cites this paper
• Altered structural connectivity and cytokine levels in Schizophrenia and Genetic high-risk individuals: Associations with disease states and vulnerability.

  2020cites this paper
• Exosomal secretion of a psychosis-altered miRNA that regulates glutamate receptor expression is affected by antipsychotics

  2019cites this paper
• The Role of the Nuclear Factor-κB Transcriptional Complex in Cortical Immune Activation in Schizophrenia.

  2019cites this paper
• Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs

  2019cites this paper
• Over-expression of TGF-β1 gene in medication free Schizophrenia.

  2019cites this paper
• Serum PGE2, 15d-PGJ, PPARγ and CRP levels in patients with schizophrenia.

  2019cites this paper
• Microglial Activation and Psychotic Disorders: Evidence from Pre-clinical and Clinical Studies.

  2019cites this paper
• Neuroinflammation and Staging

  2019cites this paper
• Shared co-expression networks in frontal cortex of the normal aged brain and schizophrenia.

  2019cites this paper
• Postmortem transcriptional profiling reveals widespread increase in inflammation in schizophrenia: a comparison of prefrontal cortex, striatum, and hippocampus among matched tetrads of controls with subjects diagnosed with schizophrenia, bipolar or major depressive disorder

  2019cites this paper
• Target Genes of Autism Risk Loci in Brain Frontal Cortex

  2019cites this paper
• Role of Infection, Autoimmunity, Atopic Disorders, and the Immune System in Schizophrenia: Evidence from Epidemiological and Genetic Studies.

  2019cites this paper
• Assessing causal links between metabolic traits, inflammation and schizophrenia: a univariable and multivariable, bidirectional Mendelian-randomization study

  2019cites this paper
• Chapter 2 The Application of Multiplex Biomarker Techniques for Improved Stratifi cation and Treatment of Schizophrenia Patients

  2018cites this paper
• Investigating the neuroimmunogenic architecture of schizophrenia

  2018cites this paper
• SAP97 regulates behavior and expression of schizophrenia risk enriched gene sets in mouse hippocampus

  2018cites this paper
• Increased circulating regulatory T cells in medicated people with schizophrenia.

  2018cites this paper
• Schizophrenia Aetiology and Drug Therapy: A Tale of Progressive Demystification and Strides in Management

  2018cites this paper
• Maternal immune activation in neurodevelopmental disorders

  2018cites this paper
• The Long Noncoding RNA Landscape in Amygdala Tissues from Schizophrenia Patients

  2018cites this paper
• Abdominal Vagal Afferents Modulate the Brain Transcriptome and Behaviors Relevant to Schizophrenia

  2018cites this paper
• Haplotypes of TNFα/β Genes Associated with Sex-Specific Paranoid Schizophrenic Risk in Tunisian Population

  2018cites this paper
• Innate immune activation of astrocytes impairs neurodevelopment via upregulation of follistatin-like 1 and interferon-induced transmembrane protein 3

  2018cites this paper
• Altered hippocampal gene expression and structure in transgenic mice overexpressing neuregulin 1 (Nrg1) type I

  2018cites this paper
• Neuroimmunomodulation in Major Depressive Disorder: Focus on Caspase 1, Inducible Nitric Oxide Synthase, and Interferon-Gamma

  2018cites this paper
• A Potential Role For Sap97 In Psychiatric Disorders

  2018cites this paper
• The association of serum nesfatin-1 and ghrelin levels with metabolic syndrome in patients with schizophrenia.

  2018cites this paper
• Plasma levels of IL‐1Ra are associated with schizophrenia

  2018influential citation
• Increased macrophages and changed brain endothelial cell gene expression in the frontal cortex of people with schizophrenia displaying inflammation

  2018cites this paper
• Reverse Engineering of Trascriptional Networks Uncovers Candidate Master Regulators Governing Neuropathology of Schizophrenia

  2017cites this paper
• Clinically proven drug targets differentially expressed in the prefrontal cortex of schizophrenia patients.

  2017cites this paper
• The Application of Multiplex Biomarker Techniques for Improved Stratification and Treatment of Schizophrenia Patients.

  2017cites this paper
• Inflammatory, cardio-metabolic and diabetic profiling of chronic schizophrenia

  2017cites this paper
• Tibolone Preserves Mitochondrial Functionality and Cell Morphology in Astrocytic Cells Treated with Palmitic Acid

  2017cites this paper
• Application of Proteomic Techniques for Improved Stratification and Treatment of Schizophrenia Patients.

  2017cites this paper
• Transcriptome sequencing study implicates immune-related genes differentially expressed in schizophrenia: new data and a meta-analysis

  2017cites this paper