Altered immune and inflammatory gene expression in prefrontal cortex of antipsychotic-free schizophrenia subjects

Gene expression studies in dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia have repeatedly reported alterations in immune and inflammatory responses as well as neuronal and mitochondrial processes. Whether the findings are due to schizophrenia and/or to the effect of antipsychotic (AP) drug exposure is particularly intriguing. In the present study, we performed a transcriptomic study in DLPFC of 16 schizophrenia subjects with no detectable AP blood levels at the time of death. Each schizophrenia subject was matched to a control subject for sex, age, postmortem interval and storage time of the samples. Weighted co-expression network analysis (WGCNA) of transcriptomic data identified 33 modules of co-expressed genes. One of these modules was significantly associated with schizophrenia diagnosis. Protein-protein interaction networks were built within the genes in the module and submitted to gene set enrichment analysis on biological processes. Results revealed the implication of immune and inflammatory responses, cytoskeleton regulation, neurotrophic factors and protein post-translational modifications. Analysis of the promoter regions of the clustered genes predicted the enrichment of 6 transcription factors, including SP1, previously associated with schizophrenia. Present results in DLPFC of AP-free schizophrenia subjects indicate that the identified biological processes, especially immune and inflammatory response alterations are representative of schizophrenia disorder and not a mere effect of acute AP exposure.