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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Autores principales:	Michael Maes, Kitiporn Plaimas, Apichat Suratanee, Cristiano Noto, Buranee Kanchanatawan
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	schizophrenia neuro-immune inflammation physiological stress bacterial translocation psychiatry Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/83878290006e4b4aa0d24367b59a2dca
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spelling	oai:doaj.org-article:83878290006e4b4aa0d24367b59a2dca2021-11-25T17:09:05ZFirst Episode Psychosis and Schizophrenia Are Systemic Neuro-Immune Disorders Triggered by a Biotic Stimulus in Individuals with Reduced Immune Regulation and Neuroprotection10.3390/cells101129292073-4409https://doaj.org/article/83878290006e4b4aa0d24367b59a2dca2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2929https://doaj.org/toc/2073-4409There 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.Michael MaesKitiporn PlaimasApichat SurataneeCristiano NotoBuranee KanchanatawanMDPI AGarticleschizophrenianeuro-immuneinflammationphysiological stressbacterial translocationpsychiatryBiology (General)QH301-705.5ENCells, Vol 10, Iss 2929, p 2929 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	schizophrenia neuro-immune inflammation physiological stress bacterial translocation psychiatry Biology (General) QH301-705.5
spellingShingle	schizophrenia neuro-immune inflammation physiological stress bacterial translocation psychiatry Biology (General) QH301-705.5 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
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.
format	article
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
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_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_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_sort	first episode psychosis and schizophrenia are systemic neuro-immune disorders triggered by a biotic stimulus in individuals with reduced immune regulation and neuroprotection
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/83878290006e4b4aa0d24367b59a2dca
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First Episode Psychosis and Schizophrenia Are Systemic Neuro-Immune Disorders Triggered by a Biotic Stimulus in Individuals with Reduced Immune Regulation and Neuroprotection

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