The study investigates the role of microglia in schizophrenia (SCZ) using human induced pluripotent stem cell-derived microglia from monozygotic twins discordant for SCZ and healthy individuals. Microglia from affected twins showed increased expression of inflammation-related genes but no significant differences in migration or phagocytic activity compared to healthy controls. Ingenuity Pathway Analysis revealed abnormalities in extracellular matrix signaling, with downregulation of extracellular matrix structure constituent Gene Ontology terms and activation of the hepatic fibrosis pathway. Upregulation of major histocompatibility complex (MHC) class II receptors was observed only in affected twin microglia. Microglia from affected twins also had a heterogeneous response to drug treatments such as clozapine, minocycline, and sulfonamide. Despite increased inflammatory gene expression, no clear signs of hyperactivation were observed in microglia from SCZ patients. The study concludes that microglia in SCZ patients exhibit gene expression aberrations related to inflammation and extracellular matrix without contributing to increased microglial activation.The study investigates the role of microglia in schizophrenia (SCZ) using human induced pluripotent stem cell-derived microglia from monozygotic twins discordant for SCZ and healthy individuals. Microglia from affected twins showed increased expression of inflammation-related genes but no significant differences in migration or phagocytic activity compared to healthy controls. Ingenuity Pathway Analysis revealed abnormalities in extracellular matrix signaling, with downregulation of extracellular matrix structure constituent Gene Ontology terms and activation of the hepatic fibrosis pathway. Upregulation of major histocompatibility complex (MHC) class II receptors was observed only in affected twin microglia. Microglia from affected twins also had a heterogeneous response to drug treatments such as clozapine, minocycline, and sulfonamide. Despite increased inflammatory gene expression, no clear signs of hyperactivation were observed in microglia from SCZ patients. The study concludes that microglia in SCZ patients exhibit gene expression aberrations related to inflammation and extracellular matrix without contributing to increased microglial activation.