The purpose of this study is to explore the correlation between ferroptosis-related genes and schizophrenia in order to explore the new direction of diagnosis and treatment of schizophrenia. We screened the datasets related to schizophrenia from the Gene Expression Comprehensive Database (GEO) and obtained ferroptosis-related genes from the FerrDB database. Bioinformatics methods were used to analyze differentially expressed genes (DEGs) and genes associated with ferroptosis-related between schizophrenia patients and healthy controls. On this basis, the hub genes were finally screened by enrichment analysis and PPI interaction analysis. Hub genes associated with ferroptosis were validated using other schizophrenia datasets in the GEO database. Finally, the hub gene-microRNA (miRNA), gene-transcription factor interaction network was constructed, and three ferroptosis-related hub genes (TP53, VEGFA and PTGS2) were screened. The validation results of these three genes in other datasets also support this conclusion. A miRNA: hsa-mir-16-5p was found to be related to the three hub genes, and pPHF8, SAP30 and lKDM5B were identified as common regulators of the three hub genes. Our results indicate that TP53, VEGFA and PTGS2 are significantly associated with schizophrenia, and may be ferroptosis-related markers of the disease.

Schizophrenia is a clinical syndrome composed of a group of symptoms involving many obstacles such as perception, thinking, emotion, behavior, and the disharmony of mental activities. Schizophrenia is one of the top ten causes of disability globally, accounting for about 1% of the global population. Previous studies have shown that schizophrenia has solid genetic characteristics. However, the diagnosis of schizophrenia mainly depends on symptomatic manifestations, and no gene can be used as a clear diagnostic marker at present. This study explored the hub genes of schizophrenia by bioinformatics analysis. Three datasets were selected and downloaded from the GEO database (GSE53987, GSE21138, and GSE27383). GEO2R, NCBI’s online analysis tool, is used to screen out significant gene expression differences. The genes were functionally enriched by GO and KEGG enrichment analysis. On this basis, the hub genes were explored through Cytoscape software, and the immune infiltration analysis and diagnostic value of the screened hub genes were judged. Finally, four hub genes (NFKBIA, CDKN1A, BTG2, GADD45B) were screened. There was a significant correlation between two hub genes (NFKBIA, BTG2) and resting memory CD4 T cells. The ROC curve results showed that all four hub genes had diagnostic value.