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Network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial

Attempts to delineate an immune subtype of schizophrenia have not yet led to the clear identification of potential treatment targets. An unbiased informatic approach at the level of individual immune cytokines and symptoms may reveal organisational structures underlying heterogeneity in schizophreni...

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Autores principales: Herniman, Sarah E., Wood, Stephen J., Khandaker, Golam, Dazzan, Paola, Pariante, Carmine M., Barnes, Nicholas M., Krynicki, Carl R., Nikkheslat, Naghmeh, Vincent, Rachel C., Roberts, Alex, Giordano, Annalisa, Watson, Andrew, Suckling, John, Barnes, Thomas R. E., Husain, Nusrat, Jones, Peter B., Joyce, Eileen, Lawrie, Stephen M., Lewis, Shôn, Deakin, Bill, Upthegrove, Rachel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10507090/
https://www.ncbi.nlm.nih.gov/pubmed/37723153
http://dx.doi.org/10.1038/s41398-023-02570-8
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author Herniman, Sarah E.
Wood, Stephen J.
Khandaker, Golam
Dazzan, Paola
Pariante, Carmine M.
Barnes, Nicholas M.
Krynicki, Carl R.
Nikkheslat, Naghmeh
Vincent, Rachel C.
Roberts, Alex
Giordano, Annalisa
Watson, Andrew
Suckling, John
Barnes, Thomas R. E.
Husain, Nusrat
Jones, Peter B.
Joyce, Eileen
Lawrie, Stephen M.
Lewis, Shôn
Deakin, Bill
Upthegrove, Rachel
author_facet Herniman, Sarah E.
Wood, Stephen J.
Khandaker, Golam
Dazzan, Paola
Pariante, Carmine M.
Barnes, Nicholas M.
Krynicki, Carl R.
Nikkheslat, Naghmeh
Vincent, Rachel C.
Roberts, Alex
Giordano, Annalisa
Watson, Andrew
Suckling, John
Barnes, Thomas R. E.
Husain, Nusrat
Jones, Peter B.
Joyce, Eileen
Lawrie, Stephen M.
Lewis, Shôn
Deakin, Bill
Upthegrove, Rachel
author_sort Herniman, Sarah E.
collection PubMed
description Attempts to delineate an immune subtype of schizophrenia have not yet led to the clear identification of potential treatment targets. An unbiased informatic approach at the level of individual immune cytokines and symptoms may reveal organisational structures underlying heterogeneity in schizophrenia, and potential for future therapies. The aim was to determine the network and relative influence of pro- and anti-inflammatory cytokines on depressive, positive, and negative symptoms. We further aimed to determine the effect of exposure to minocycline or placebo for 6 months on cytokine-symptom network connectivity and structure. Network analysis was applied to baseline and 6-month data from the large multi-center BeneMin trial of minocycline (N = 207) in schizophrenia. Pro-inflammatory cytokines IL-6, TNF-α, and IFN-γ had the greatest influence in the inflammatory network and were associated with depressive symptoms and suspiciousness at baseline. At 6 months, the placebo group network connectivity was 57% stronger than the minocycline group, due to significantly greater influence of TNF-α, early wakening, and pathological guilt. IL-6 and its downstream impact on TNF-α, and IFN-γ, could offer novel targets for treatment if offered at the relevant phenotypic profile including those with depression. Future targeted experimental studies of immune-based therapies are now needed.
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spelling pubmed-105070902023-09-20 Network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial Herniman, Sarah E. Wood, Stephen J. Khandaker, Golam Dazzan, Paola Pariante, Carmine M. Barnes, Nicholas M. Krynicki, Carl R. Nikkheslat, Naghmeh Vincent, Rachel C. Roberts, Alex Giordano, Annalisa Watson, Andrew Suckling, John Barnes, Thomas R. E. Husain, Nusrat Jones, Peter B. Joyce, Eileen Lawrie, Stephen M. Lewis, Shôn Deakin, Bill Upthegrove, Rachel Transl Psychiatry Article Attempts to delineate an immune subtype of schizophrenia have not yet led to the clear identification of potential treatment targets. An unbiased informatic approach at the level of individual immune cytokines and symptoms may reveal organisational structures underlying heterogeneity in schizophrenia, and potential for future therapies. The aim was to determine the network and relative influence of pro- and anti-inflammatory cytokines on depressive, positive, and negative symptoms. We further aimed to determine the effect of exposure to minocycline or placebo for 6 months on cytokine-symptom network connectivity and structure. Network analysis was applied to baseline and 6-month data from the large multi-center BeneMin trial of minocycline (N = 207) in schizophrenia. Pro-inflammatory cytokines IL-6, TNF-α, and IFN-γ had the greatest influence in the inflammatory network and were associated with depressive symptoms and suspiciousness at baseline. At 6 months, the placebo group network connectivity was 57% stronger than the minocycline group, due to significantly greater influence of TNF-α, early wakening, and pathological guilt. IL-6 and its downstream impact on TNF-α, and IFN-γ, could offer novel targets for treatment if offered at the relevant phenotypic profile including those with depression. Future targeted experimental studies of immune-based therapies are now needed. Nature Publishing Group UK 2023-09-18 /pmc/articles/PMC10507090/ /pubmed/37723153 http://dx.doi.org/10.1038/s41398-023-02570-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Herniman, Sarah E.
Wood, Stephen J.
Khandaker, Golam
Dazzan, Paola
Pariante, Carmine M.
Barnes, Nicholas M.
Krynicki, Carl R.
Nikkheslat, Naghmeh
Vincent, Rachel C.
Roberts, Alex
Giordano, Annalisa
Watson, Andrew
Suckling, John
Barnes, Thomas R. E.
Husain, Nusrat
Jones, Peter B.
Joyce, Eileen
Lawrie, Stephen M.
Lewis, Shôn
Deakin, Bill
Upthegrove, Rachel
Network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial
title Network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial
title_full Network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial
title_fullStr Network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial
title_full_unstemmed Network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial
title_short Network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial
title_sort network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10507090/
https://www.ncbi.nlm.nih.gov/pubmed/37723153
http://dx.doi.org/10.1038/s41398-023-02570-8
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