Muscarinic receptors downregulation is associated with increased IL6 expression in brain samples of individuals with schizophrenia

Muscarinic receptors downregulation is associated with increased IL6 expression in brain samples of individuals with schizophrenia | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 16 May 2025 V1 Latest version Share on Muscarinic receptors downregulation is associated with increased IL6 expression in brain samples of individuals with schizophrenia Authors : Hadar Sharabi Goldenberg 0009-0006-6940-0688 , Assif Yitzhaky , and Libi Hertzberg 0000-0002-7895-8089 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174736650.05448372/v1 222 views 122 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Acetylcholine plays a role in the immune system with notable anti-inflammatory properties. Xanomeline, a muscarinic acetylcholine receptor agonist, was recently approved for schizophrenia, marking the first therapy of its kind. Evidence suggests two molecular subtypes of schizophrenia: one characterized by reduced muscarinic receptor expression (muscarinic receptor-deficit schizophrenia, MRDS), and another marked by elevated immune markers, such as Interleukin-6 (IL-6), indicating immune activation. While IL-6 was consistently found to be upregulated in schizophrenia, findings on muscarinic receptor expression have been inconsistent.To explore the relationship between muscarinic receptor genes and IL6 expression, we conducted a systematic meta-analysis of CHRM1-5 and IL6 in postmortem brain samples of patients with schizophrenia. Following PRISMA guidelines, seven independent datasets met our inclusion criteria, comprising 295 samples (151 schizophrenia,144 controls). Our analysis revealed overall CHRM1-5 genes downregulation, with significant downregulation of CHRM1 and CHRM2, alongside upregulation of IL6. Notably, CHRM1 expression showed significant negative correlations with IL6 and its receptors, suggesting an overlap between MRDS and the immune-activated schizophrenia subgroup. This subgroup may benefit from personalized therapies, including Xanomeline or immune system modulators. Further research is required to confirm these findings and investigate targeted treatments. Supplementary Material File (28.04 final version.docx) Download 1.06 MB Information & Authors Information Version history V1 Version 1 16 May 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords chrm gene expression immune system muscarinic receptor-deficit schizophrenia Authors Affiliations Hadar Sharabi Goldenberg 0009-0006-6940-0688 Tel Aviv University View all articles by this author Assif Yitzhaky Weizmann Institute of Science View all articles by this author Libi Hertzberg 0000-0002-7895-8089 [email protected] Tel Aviv University Sackler Faculty of Medicine View all articles by this author Metrics & Citations Metrics Article Usage 222 views 122 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Hadar Sharabi Goldenberg, Assif Yitzhaky, Libi Hertzberg. Muscarinic receptors downregulation is associated with increased IL6 expression in brain samples of individuals with schizophrenia. Authorea . 16 May 2025. DOI: https://doi.org/10.22541/au.174736650.05448372/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. 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