AUTHOR=Yao Gaolei , Zeng Jingchun , Huang Yuan , Lu Huipeng , Ping Junjiao , Wan Jing , Jiang Tingyun , Deng Fuyuan , Li Chenyun , Liu Xinxia , Tang Chunzhi , Lu Liming 

TITLE=Discovery of biological markers for schizophrenia based on metabolomics: a systematic review

JOURNAL=Frontiers in Psychiatry

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1540260

DOI=10.3389/fpsyt.2025.1540260

ISSN=1664-0640

ABSTRACT=Introduction and methodsTo discover biomarkers for schizophrenia (SCZ) at the metabolomics level, we registered this systematic review (CRD42024572133 (https://www.crd.york.ac.uk/PROSPERO/home)) including 56 qualified articles, and we identified the characteristics of metabolites, metabolite combinations, and metabolic pathways associated with SCZ.ResultsOur findings showed that decreased arachidonic acid, arginine, and aspartate levels, and the increased levels of glucose 6-phosphate and glycylglycine were associated with the onset of SCZ. Metabolites such as carnitine and methionine sulfoxide not only helped to identify SCZ in Miao patients, but also were different between Miao patients and Han patients. The decrease in benzoic acid and betaine and the increase in creatine were the notable metabolic characteristics of first-episode schizophrenia (FESCZ). The metabolite combination formed by metabolites such as methylamine, dimethylamine and other metabolites had the best diagnostic effect. Arginine and proline metabolism and arginine biosynthesis had a clear advantage in identifying SCZ and acute SCZ. Butanoate metabolism played an important role in identifying SCZ, toxoplasma infection and SCZ comorbidity. Biosynthesis of unsaturated fatty acids was also significantly enriched in the diagnosis and treatment of SCZ.DiscussionThis study summarizes the current progress in clinical metabolomic research related to SCZ, deepens  understanding of the pathogenesis of SCZ, and lays a foundation for subsequent research on SCZ-related metabolites.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/home, identifier CRD42024572133.