Inflammation and viral infection as disease modifiers in schizophrenia

Numerous studies have now implicated a role for inflammation in schizophrenia. However, many aspects surrounding this aspect of the disease are still controversial. This controversy has been driven by conflicting evidence on the role of both pro-and anti-inflammatory factors and by often contentious...

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Autores principales: Klein, Hans C., Guest, Paul C., Dobrowolny, Henrik, Steiner, Johann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577328/
https://www.ncbi.nlm.nih.gov/pubmed/37850104
http://dx.doi.org/10.3389/fpsyt.2023.1231750
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author Klein, Hans C.
Guest, Paul C.
Dobrowolny, Henrik
Steiner, Johann
author_facet Klein, Hans C.
Guest, Paul C.
Dobrowolny, Henrik
Steiner, Johann
author_sort Klein, Hans C.
collection PubMed
description Numerous studies have now implicated a role for inflammation in schizophrenia. However, many aspects surrounding this aspect of the disease are still controversial. This controversy has been driven by conflicting evidence on the role of both pro-and anti-inflammatory factors and by often contentious findings concerning cytokine and immune cell profiles in the central nervous system and periphery. Current evidence supports the point that interleukin-6 is elevated in CSF, but does not support activation of microglia, resident macrophage-like cells in the brain. Furthermore, the mechanisms involving transit of the peripheral immune system factors across the blood brain barrier to central parenchyma have still not been completely elucidated. This process appears to involve perivascular macrophages and accompanying dendritic cells retained in the parenchyma by the chemokine and cytokine composition of the surrounding milieu. In addition, a number of studies have shown that this can be modulated by infection with viruses such as herpes simplex virus type I which may disrupt antigen presentation in the perivascular space, with long-lasting consequences. In this review article, we discuss the role of inflammation and viral infection as potential disease modifiers in schizophrenia. The primary viral hit may occur in the fetus in utero, transforming the immune response regulatory T-cells or the virus may secondarily remain latent in immune cells or neurons and modify further immune responses in the developing individual. It is hoped that unraveling this pathway further and solidifying our understanding of the pathophysiological mechanisms involved will pave the way for future studies aimed at identification and implementation of new biomarkers and drug targets. This may facilitate the development of more effective personalized therapies for individuals suffering with schizophrenia.
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spelling pubmed-105773282023-10-17 Inflammation and viral infection as disease modifiers in schizophrenia Klein, Hans C. Guest, Paul C. Dobrowolny, Henrik Steiner, Johann Front Psychiatry Psychiatry Numerous studies have now implicated a role for inflammation in schizophrenia. However, many aspects surrounding this aspect of the disease are still controversial. This controversy has been driven by conflicting evidence on the role of both pro-and anti-inflammatory factors and by often contentious findings concerning cytokine and immune cell profiles in the central nervous system and periphery. Current evidence supports the point that interleukin-6 is elevated in CSF, but does not support activation of microglia, resident macrophage-like cells in the brain. Furthermore, the mechanisms involving transit of the peripheral immune system factors across the blood brain barrier to central parenchyma have still not been completely elucidated. This process appears to involve perivascular macrophages and accompanying dendritic cells retained in the parenchyma by the chemokine and cytokine composition of the surrounding milieu. In addition, a number of studies have shown that this can be modulated by infection with viruses such as herpes simplex virus type I which may disrupt antigen presentation in the perivascular space, with long-lasting consequences. In this review article, we discuss the role of inflammation and viral infection as potential disease modifiers in schizophrenia. The primary viral hit may occur in the fetus in utero, transforming the immune response regulatory T-cells or the virus may secondarily remain latent in immune cells or neurons and modify further immune responses in the developing individual. It is hoped that unraveling this pathway further and solidifying our understanding of the pathophysiological mechanisms involved will pave the way for future studies aimed at identification and implementation of new biomarkers and drug targets. This may facilitate the development of more effective personalized therapies for individuals suffering with schizophrenia. Frontiers Media S.A. 2023-10-02 /pmc/articles/PMC10577328/ /pubmed/37850104 http://dx.doi.org/10.3389/fpsyt.2023.1231750 Text en Copyright © 2023 Klein, Guest, Dobrowolny and Steiner. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Klein, Hans C.
Guest, Paul C.
Dobrowolny, Henrik
Steiner, Johann
Inflammation and viral infection as disease modifiers in schizophrenia
title Inflammation and viral infection as disease modifiers in schizophrenia
title_full Inflammation and viral infection as disease modifiers in schizophrenia
title_fullStr Inflammation and viral infection as disease modifiers in schizophrenia
title_full_unstemmed Inflammation and viral infection as disease modifiers in schizophrenia
title_short Inflammation and viral infection as disease modifiers in schizophrenia
title_sort inflammation and viral infection as disease modifiers in schizophrenia
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577328/
https://www.ncbi.nlm.nih.gov/pubmed/37850104
http://dx.doi.org/10.3389/fpsyt.2023.1231750
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