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A case-control study assessed associations between mRNA expression levels and schizophrenia, screening neural signaling pathway genes by RNA sequencing in a small cohort and validating findings in 217 cases and 217 controls. Differential expression and restricted cubic spline regression informed gene expression score construction and evaluation of diagnostic performance, including risk correlations and model discrimination improvements.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/differentially-expressed-mrnas-of-neural-signaling-pathway-genes-in-peripheral-blood-leukocytes-as-biomarkers-for-schizophrenia/450268/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/differentially-expressed-mrnas-of-neural-signaling-pathway-genes-in-peripheral-blood-leukocytes-as-biomarkers-for-schizophrenia/450268.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-05","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why are neural signaling pathway mRNAs investigated as biomarkers for schizophrenia?","Question",{"text":112,"@type":113},"The study links schizophrenia biology to abnormal neurotransmitter regulation and neural signaling pathway dysfunction. It also argues that peripheral blood leukocytes can reflect aspects of central nervous system molecular changes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were the candidate mRNAs identified and validated?",{"text":117,"@type":113},"Differentially expressed neural signaling pathway mRNAs were screened by RNA sequencing in a small set of schizophrenia patients and controls. A larger validation case-control cohort (217 cases and 217 controls) then verified the differential expression findings.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the gene expression score (GES) contribute to diagnostic evaluation?",{"text":121,"@type":113},"GES aggregates expression information from differentially expressed genes to quantify diagnostic signal. Incorporating seven genes into the GES improved model discrimination, reported as a higher area under the curve.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},450268,1790870334,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":34,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","ARTICLE OPEN   \nDifferentially expressed mRNAs of neural signaling pathway genes in peripheral blood leukocytes as biomarkers for schizophrenia  \nYuan Zhou 1,4, Mengya Zhu 2,4, Yao Fan 3, Feifan Wang 1, Siqing Mi 1, Chong Shen 1 ✉ and Yong Xue 2 ✉  \n|  |  |  |\n| --- | --- | --- |\n|  | Abnormal neurotransmitter regulation plays a role in the pathogenesis of Schizophrenia (SCZ), and the presence of brain tissue-like aberrant expression in the partial transcriptome of peripheral blood leukocytes from patients with SCZ suggests that these aberrantly expressed genes could be potential diagnostic markers. We designed a case-control study to analyze the association between the expression levels of mRNAs and SCZ in peripheral blood leukocytes and to explore their potential value as diagnostic biomarkers for SCZ. Differentially expressed mRNAs associated with neural signaling pathways were screened by RNA sequencing in a small set, comprising 9 patients with SCZ and 20 controls. A case-control study that included 217 cases and 217 controls was further conducted to verify these mRNAs. The differential expression analysis between cases and controls was performed, followed by restricted cubic spline regression analysis. Gene expression score (GES) was constructed for differentially expressed genes to assess their diagnostic value as biomarkers. In SCZ patients, there were higher expression levels of CREB5, PPP3R1 and PPP1CB (P \u003C 0.05) than in controls. Furthermore, DUSP1 and MAPK13 downregulated in undifferentiated SCZ and acute schizophrenia-like psychotic disorder (P \u003C 0.05), PPP3R1 expression upregulated in paranoid SCZ, undifferentiated SCZ and acute schizophrenia-like psychotic disorder (P \u003C 0.01), and CREB5 exclusively upregulated in paranoid SCZ (P = 0.001), respectively. The risk of SCZ was nonlinearly correlated with DUSP1, GNG10, GNG7, PRKACA, CREB5, PPP3R1 and PPP1CB (Poverall \u003C 0.05, Pnonlinear \u003C 0.05) . Meanwhile, incorporating these 7 genes into the GES improved the model’s area under curve to 0 743, significantly enhancing the diagnostic |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| .\u003Cbr>discriminatory ability for SCZ. |  |  |\n|  |  |  |\n|  | Schizophrenia (2026)12:6; [https://doi.org/10.1038/s41537-025-00709-8](https://doi.org/10.1038/s41537-025-00709-8) |  |\n|  |  |  |\n\nINTRODUCTION  \nSchizophrenia (SCZ) is a neurological disorder that frequently manifests as both positive and negative symptoms in addition to aberrant cognitive functioning. SCZ usually develops in late adolescence or early adulthood, and males are more likely to develop SCZ than females1–3. For patients with SCZ, early diagnosis and treatment can help improve clinical symptoms, reduce illness suffering, improve quality of life, and extend life expectancy4. However, the current diagnosis of SCZ relies primarily on clinical assessment, which is subjective and may lead to misdiagnosis or delayed intervention. Given these limitations, there is an urgent need to identify objective biomarkers to improve diagnostic accuracy and facilitate treatment.  \nAlthough the precise cause of SCZ remains unknown, abnormalities in neural signaling pathways, such as abnormal dopamine system, have been accepted as a major contribution to SCZ symptoms5–7. Mood, cognition, sleep and other physiological and behavioral features are influenced by the 5-hydroxytryptamine (5-HT) regulation in the central nervous system8–10. The glutamate hypothesis proposes that SCZ may be linked to abnormal function of the glutamate system, a key neurotransmitter involved in learning, emotion regulation and cognitive processes 11–13.  \nSCZ is a central nervous system disorder and brain tissue samples are not easily available. Therefore, peripheral blood mononuclear cells (PBMCs) can be a useful research vehicle for SCZ because they are easily available and can reveal some  \nmolecular changes in the ","cbCaid55yJhjP3kU","https://ap.wps.com/l/cbCaid55yJhjP3kU","pdf",920578,"English","# Introduction\n## Background and unmet diagnostic needs\n## Rationale for peripheral blood and neural signaling pathways\n# Methods\n## Subjects","[{\"question\":\"Why are neural signaling pathway mRNAs investigated as biomarkers for schizophrenia?\",\"answer\":\"The study links schizophrenia biology to abnormal neurotransmitter regulation and neural signaling pathway dysfunction. It also argues that peripheral blood leukocytes can reflect aspects of central nervous system molecular changes.\"},{\"question\":\"How were the candidate mRNAs identified and validated?\",\"answer\":\"Differentially expressed neural signaling pathway mRNAs were screened by RNA sequencing in a small set of schizophrenia patients and controls. A larger validation case-control cohort (217 cases and 217 controls) then verified the differential expression findings.\"},{\"question\":\"How does the gene expression score (GES) contribute to diagnostic evaluation?\",\"answer\":\"GES aggregates expression information from differentially expressed genes to quantify diagnostic signal. Incorporating seven genes into the GES improved model discrimination, reported as a higher area under the curve.\"}]","Differentially expressed mRNAs of neural signaling pathway genes in peripheral blood leukocytes as biomarkers for schizophrenia | PDF",1790732676,18]