Schizophrenia Pathophysiology: Neurotransmitter Dysfunctions and Biomarker Frontiers

Schizophrenia Pathophysiology: Neurotransmitter Dysfunctions and Biomarker Frontiers | 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 Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed.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. 30 October 2025 V2 Latest version Share on Schizophrenia Pathophysiology: Neurotransmitter Dysfunctions and Biomarker Frontiers Authors : Acharya Balkrishna , Sumit Kumar Singh 0000-0001-5941-111X , Sonam Verma 0000-0002-6323-9284 [email protected] , Pratha Bora , Vidhi Dobhal , and Vedpriya Arya Authors Info & Affiliations https://doi.org/10.22541/au.169296182.23817881/v2 Published Current Topics in Medicinal Chemistry Version of record Peer review timeline 485 views 139 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Schizophrenia is a heterogeneous chronic brain disorder driven by multiple pathophysiological processes. While dopaminergic theories dominate current therapies, emerging evidence highlights glutamatergic dysregulation, particularly N-methyl-D-aspartate receptor (NMDAR) hypofunction, as a key mechanism alongside dopaminergic, serotonergic, and neurodevelopmental pathways. This article synthesizes mechanistic insights, focusing on neurotransmitter disruptions, oxidative stress, neuroinflammation, and Wnt signaling, to elucidate the clinical diversity of schizophrenia and identify biomarkers for precise diagnostics and therapeutics. Methods: A comprehensive literature search was conducted using Web of Science, Scopus, Google Scholar, and PubMed, with keywords including “schizophrenia,” “psychosis,” “pathophysiology,” “mechanism,” and “biomarker.” Studies were selected to explore NMDAR hypofunction, glutamatergic dysregulation, and associated signaling pathways, integrating preclinical and human data to map circuit-based interactions and biomarker profiles. Results: We present a novel circuit-based model of schizophrenia pathophysiology, centered on NMDAR hypofunction and glutamatergic dysregulation, integrating dopaminergic, GABAergic, and inflammatory pathways. Key biomarkers, including inflammatory (e.g., high-sensitivity Creactive protein [hs-CRP], interleukin-6 [IL-6]), neurochemical (e.g., brain-derived neurotrophic factor [BDNF]), and functional (e.g., mismatch negativity [MMN]), are categorized by symptomatic domains and clinical stages, providing diagnostic and prognostic insights. Discussions: The findings underscore NMDAR hypofunction’s role in driving schizophrenia’s symptomatic spectrum, though its interplay with other pathways highlights the disorder’s complexity. Neuronal loss, although not universal, is context-specific (e.g., hippocampal interneurons), complementing functional biomarkers such as MMN. Limitations include the need for robust human validation of biomarkers and broader exploration of non-glutamatergic mechanisms. Conclusion: Considering the multifaceted nature of the disorder, our emphasis on the NMDAR hypofunction model can help explain many of the synergies involved among the seemingly independent dysregulated events. This is a caption Information & Authors Information Version history V1 Version 1 25 August 2023 V2 Version 2 30 October 2025 Peer review timeline Published Current Topics in Medicinal Chemistry Version of Record 28 Oct 2025 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords biomarkers cns interactive mechanism schizophrenia signaling dysregulations Authors Affiliations Acharya Balkrishna University of Patanjali Patanjali Research Foundation View all articles by this author Sumit Kumar Singh 0000-0001-5941-111X Patanjali Research Institute View all articles by this author Sonam Verma 0000-0002-6323-9284 [email protected] Patanjali Research Institute View all articles by this author Pratha Bora Patanjali Research Institute View all articles by this author Vidhi Dobhal Patanjali Research Institute View all articles by this author Vedpriya Arya Patanjali Research Foundation University of Patanjali View all articles by this author Metrics & Citations Metrics Article Usage 485 views 139 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Acharya Balkrishna, Sumit Kumar Singh, Sonam Verma, et al. Schizophrenia Pathophysiology: Neurotransmitter Dysfunctions and Biomarker Frontiers. Authorea . 30 October 2025. DOI: https://doi.org/10.22541/au.169296182.23817881/v2 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. 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