First Episode Psychosis and Schizophrenia Are Systemic Neuro-Immune Disorders Triggered by a Biotic Stimulus in Individuals with Reduced Immune Regulation and Neuroprotection
There is evidence that schizophrenia is characterized by activation of the immune-inflammatory response (IRS) and compensatory immune-regulatory systems (CIRS) and lowered neuroprotection. Studies performed on antipsychotic-naïve first episode psychosis (AN-FEP) and schizophrenia (FES) patients are...
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| Format: | Article |
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MDPI AG
2021-10-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/11/2929 |
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| author | Michael Maes Kitiporn Plaimas Apichat Suratanee Cristiano Noto Buranee Kanchanatawan |
| author_facet | Michael Maes Kitiporn Plaimas Apichat Suratanee Cristiano Noto Buranee Kanchanatawan |
| author_sort | Michael Maes |
| collection | DOAJ |
| description | There is evidence that schizophrenia is characterized by activation of the immune-inflammatory response (IRS) and compensatory immune-regulatory systems (CIRS) and lowered neuroprotection. Studies performed on antipsychotic-naïve first episode psychosis (AN-FEP) and schizophrenia (FES) patients are important as they may disclose the pathogenesis of FES. However, the protein–protein interaction (PPI) network of FEP/FES is not established. The aim of the current study was to delineate a) the characteristics of the PPI network of AN-FEP and its transition to FES; and b) the biological functions, pathways, and molecular patterns, which are over-represented in FEP/FES. Toward this end, we used PPI network, enrichment, and annotation analyses. FEP and FEP/FES are strongly associated with a response to a bacterium, alterations in Toll-Like Receptor-4 and nuclear factor-κB signaling, and the Janus kinases/signal transducer and activator of the transcription proteins pathway. Specific molecular complexes of the peripheral immune response are associated with microglial activation, neuroinflammation, and gliogenesis. FEP/FES is accompanied by lowered protection against inflammation, in part attributable to dysfunctional miRNA maturation, deficits in neurotrophin and Wnt/catenin signaling, and adherens junction organization. Multiple interactions between reduced brain derived neurotrophic factor, E-cadherin, and β-catenin and disrupted schizophrenia-1 (DISC1) expression increase the vulnerability to the neurotoxic effects of immune molecules, including cytokines and complement factors. In summary: FEP and FES are systemic neuro-immune disorders that are probably triggered by a bacterial stimulus which induces neuro-immune toxicity cascades that are overexpressed in people with reduced anti-inflammatory and miRNA protections, cell–cell junction organization, and neurotrophin and Wnt/catenin signaling. |
| first_indexed | 2024-03-10T05:37:28Z |
| format | Article |
| id | doaj.art-83878290006e4b4aa0d24367b59a2dca |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T05:37:28Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-83878290006e4b4aa0d24367b59a2dca2023-11-22T22:48:49ZengMDPI AGCells2073-44092021-10-011011292910.3390/cells10112929First Episode Psychosis and Schizophrenia Are Systemic Neuro-Immune Disorders Triggered by a Biotic Stimulus in Individuals with Reduced Immune Regulation and NeuroprotectionMichael Maes0Kitiporn Plaimas1Apichat Suratanee2Cristiano Noto3Buranee Kanchanatawan4Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandAdvanced Virtual and Intelligent Computing (AVIC) Center, Department of Mathematics and Computer Science, Faculty of Science, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Mathematics, Faculty of Applied Science, King Mongkut’s University of Technology North Bangkok, Bangkok 10800, ThailandGAPi (Early Psychosis Group), Universidade Federal de São Paulo (UNIFESP), São Paulo 04021-001, BrazilDepartment of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandThere is evidence that schizophrenia is characterized by activation of the immune-inflammatory response (IRS) and compensatory immune-regulatory systems (CIRS) and lowered neuroprotection. Studies performed on antipsychotic-naïve first episode psychosis (AN-FEP) and schizophrenia (FES) patients are important as they may disclose the pathogenesis of FES. However, the protein–protein interaction (PPI) network of FEP/FES is not established. The aim of the current study was to delineate a) the characteristics of the PPI network of AN-FEP and its transition to FES; and b) the biological functions, pathways, and molecular patterns, which are over-represented in FEP/FES. Toward this end, we used PPI network, enrichment, and annotation analyses. FEP and FEP/FES are strongly associated with a response to a bacterium, alterations in Toll-Like Receptor-4 and nuclear factor-κB signaling, and the Janus kinases/signal transducer and activator of the transcription proteins pathway. Specific molecular complexes of the peripheral immune response are associated with microglial activation, neuroinflammation, and gliogenesis. FEP/FES is accompanied by lowered protection against inflammation, in part attributable to dysfunctional miRNA maturation, deficits in neurotrophin and Wnt/catenin signaling, and adherens junction organization. Multiple interactions between reduced brain derived neurotrophic factor, E-cadherin, and β-catenin and disrupted schizophrenia-1 (DISC1) expression increase the vulnerability to the neurotoxic effects of immune molecules, including cytokines and complement factors. In summary: FEP and FES are systemic neuro-immune disorders that are probably triggered by a bacterial stimulus which induces neuro-immune toxicity cascades that are overexpressed in people with reduced anti-inflammatory and miRNA protections, cell–cell junction organization, and neurotrophin and Wnt/catenin signaling.https://www.mdpi.com/2073-4409/10/11/2929schizophrenianeuro-immuneinflammationphysiological stressbacterial translocationpsychiatry |
| spellingShingle | Michael Maes Kitiporn Plaimas Apichat Suratanee Cristiano Noto Buranee Kanchanatawan First Episode Psychosis and Schizophrenia Are Systemic Neuro-Immune Disorders Triggered by a Biotic Stimulus in Individuals with Reduced Immune Regulation and Neuroprotection Cells schizophrenia neuro-immune inflammation physiological stress bacterial translocation psychiatry |
| title | First Episode Psychosis and Schizophrenia Are Systemic Neuro-Immune Disorders Triggered by a Biotic Stimulus in Individuals with Reduced Immune Regulation and Neuroprotection |
| title_full | First Episode Psychosis and Schizophrenia Are Systemic Neuro-Immune Disorders Triggered by a Biotic Stimulus in Individuals with Reduced Immune Regulation and Neuroprotection |
| title_fullStr | First Episode Psychosis and Schizophrenia Are Systemic Neuro-Immune Disorders Triggered by a Biotic Stimulus in Individuals with Reduced Immune Regulation and Neuroprotection |
| title_full_unstemmed | First Episode Psychosis and Schizophrenia Are Systemic Neuro-Immune Disorders Triggered by a Biotic Stimulus in Individuals with Reduced Immune Regulation and Neuroprotection |
| title_short | First Episode Psychosis and Schizophrenia Are Systemic Neuro-Immune Disorders Triggered by a Biotic Stimulus in Individuals with Reduced Immune Regulation and Neuroprotection |
| title_sort | first episode psychosis and schizophrenia are systemic neuro immune disorders triggered by a biotic stimulus in individuals with reduced immune regulation and neuroprotection |
| topic | schizophrenia neuro-immune inflammation physiological stress bacterial translocation psychiatry |
| url | https://www.mdpi.com/2073-4409/10/11/2929 |
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