Conclusions

The pursuit of effective diagnostic biomarkers for schizophrenia spectrum disorders (SSD) poses a formidable challenge, given the intricate and interconnected changes occurring throughout the body. This review aimed to scrutinize biomarkers associated with hypotheses regarding the pathophysiology of SSD that underwent ROC curve analysis in the last 12 years (2011–2023). The goal was to pinpoint prevalent biomarkers within developed models, potentially forming a distinctive biomarker signature for SSD. While China led in over 50% of the studies, representation from more than 20 countries, including a substantial cohort of over 10,000 patients diagnosed with SSD, underscores the global scope of this research. Biomarkers linked to neurotrophic, neuroendocrine, and immunoinflammatory processes exhibited moderate performance. The most promising scenarios emerged when models incorporated 3–10 metabolic biomarkers from diverse chemical classes and pathways. Through the analysis of models incorporating human metabolic biomarkers, a list of 19 peripheral metabolites surfaced. In disease-directed enrichment analysis, this metabolite panel secured the second position for SSD with notable significance. Similarly, the compilation of metabolites associated with the gut microbiota derived a list of eight peripheral amino acids that yielded a comparable outcome. This list is suggested for incorporation into future targeted metabolomics studies for diagnosing SSD.