ArticleTranslational psychiatry2019
Dysregulation of a specific immune-related network of genes biologically defines a subset of schizophrenia.
Article in Translational psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.
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Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- Changes in peripheral blood compounds following psychopharmacological treatment in drug-naïve first-episode patients with either schizophrenia or major depressive disorder: a meta-analysis.Psychological medicine · 2021Pooled it
- Peripheral Blood-Based Gene Expression Studies in Schizophrenia: A Systematic Review.Frontiers in genetics · 2021Pooled it
- A double-blind, randomized controlled study of the effects of celecoxib on clinical symptoms and cognitive impairment in patients with drug-naïve first episode schizophrenia: pharmacogenetic impact of cyclooxygenase-2 functional polymorphisms.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Trial
- Effect of Chronic Stress on Whole Blood Transcriptome: A Meta-Analysis of Publicly Available Datasets from Rodent Models.bioRxiv : the preprint server for biology · 2025Article
- The future of diagnosis in clinical neurosciences: Comparing multiple sclerosis and schizophrenia.European psychiatry : the journal of the Association of European Psychiatrists · 2023Review
- Cognitive and functional deficits are associated with white matter abnormalities in two independent cohorts of patients with schizophrenia.European archives of psychiatry and clinical neuroscience · 2022Article
- Synapse-specific roles for microglia in development: New horizons in the prefrontal cortex.Frontiers in molecular neuroscience · 2022Review
- Schizophrenia Hypothesis: Autonomic Nervous System Dysregulation of Fetal and Adult Immune Tolerance.Frontiers in systems neuroscience · 2022Article
- Pharmaco-Magnetic Resonance as a Tool for Monitoring the Medication-Related Effects in the Brain May Provide Potential Biomarkers for Psychotic Disorders.International journal of molecular sciences · 2021Review
- Inflammatory processes linked to major depression and schizophrenic disorders and the effects of polypharmacy in psychiatry: evidence from a longitudinal study of 279 patients under therapy.European archives of psychiatry and clinical neuroscience · 2021Observational
- Translational Application of a Neuro-Scientific Multi-Modal Approach Into Forensic Psychiatric Evaluation: Why and How?Frontiers in psychiatry · 2021Article
- From sequence to information.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Review
- Cocaine Administration and Its Abstinence Conditions Modulate Neuroglia.International journal of molecular sciences · 2020Article
- The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation.Frontiers in cellular neuroscience · 2020Review
- Loci Associated With Antibody Response in Feral Swine (Frontiers in veterinary science · 2020Article
- Heterogeneous trajectories in schizophrenia: insights from neurodevelopment and neuroprogression models.Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)Review
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently, the clinical diagnosis of schizophrenia relies solely on self-reporting and clinical interview, and likely comprises heterogeneous biological subsets. Such subsets may be defined by an underlying biology leading to solid biomarkers. A transgenic rat model modestly overexpressing the full-length, non-mutant Disrupted-in-Schizophrenia 1 (DISC1) protein (tgDISC1 rat) was generated that defines such a subset, inspired by our previous identification of insoluble DISC1 protein in post mortem brains from patients with chronic mental illness. Besides specific phenotypes such as DISC1 protein pathology, abnormal dopamine homeostasis, and changes in neuroanatomy and behavior, this animal model also shows subtle disturbances in overarching signaling pathways relevant for schizophrenia. In a reverse-translational approach, assuming that both the animal model and a patient subset share common disturbed signaling pathways, we identified differentially expressed transcripts from peripheral blood mononuclear cells of tgDISC1 rats that revealed an interconnected set of dysregulated genes, led by decreased expression of regulator of G-protein signaling 1 (RGS1), chemokine (C-C) ligand 4 (CCL4), and other immune-related transcripts enriched in T-cell and macrophage signaling and converging in one module after weighted gene correlation network analysis. Testing expression of this gene network in two independent cohorts of patients with schizophrenia versus healthy controls (n = 16/50 and n = 54/45) demonstrated similar expression changes. The two top markers RGS1 and CCL4 defined a subset of 27% of patients with 97% specificity. Thus, analogous aberrant signaling pathways can be identified by a blood test in an animal model and a corresponding schizophrenia patient subset, suggesting that in this animal model tailored pharmacotherapies for this patient subset could be achieved.
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