Inflammation-related genes up-regulated in schizophrenia brains

Background: Multiple studies have shown that brain gene expression is disturbed in subjects suffering from schizophrenia. However, disentangling disease effects from alterations caused by medication is a challenging task. The main goal of this study is to find transcriptional alterations in schizophrenia that are independent of neuroleptic treatment. Methods: We compared the transcriptional profiles in brain autopsy samples from 55 control individuals with that from 55 schizophrenic subjects, subdivided according to the type of antipsychotic medication received. Results: Using global and high- resolution mRNA quantification techniques, we show that genes involved in immune response ( GO: 0006955) are up regulated in all groups of patients, including those not treated at the time of death. In particular, IFITM2, IFITM3, SERPINA3, and GBP1 showed increased mRNA levels in schizophrenia ( p- values from qPCR = 0.01). These four genes were coexpressed in both schizophrenic subjects and controls. In- vitro experiments suggest that these genes are expressed in both oligodendrocyte and endothelial cells, where transcription is inducible by the inflammatory cytokines TNF-alpha, IFN-alpha and IFN-gamma. Conclusion: Although the modified genes are not classical indicators of chronic or acute inflammation, our results indicate alterations of inflammation- related pathways in schizophrenia. In addition, the observation in oligodendrocyte cells suggests that alterations in inflammatory- related genes may have consequences for myelination. Our findings encourage future research to explore whether anti- inflammatory agents can be used in combination with traditional antipsychotics for a more efficient treatment of schizophrenia.