Maternal immune activation induces methylation changes in schizophrenia genes

Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Infection driven maternal immune activation (MIA) during pregnancy is a key environmental risk factor. However, little is known about how MIA during pregnancy could contribute to adult-onset schizophrenia. In this study, we investigated if maternal immune activation induces changes in methylation of genes linked to schizophrenia. We found that differentially expressed genes in schizophrenia brain were significantly enriched among MIA induced differentially methylated genes in the foetal brain in a cell-type-specific manner. Upregulated genes in layer V pyramidal neurons were enriched among hypomethylated genes at gestational day 9 (fold change = 1.57, FDR = 0.049) and gestational day 17 (fold change = 1.97, FDR = 0.0006). A linear regression analysis, which showed a decrease in gene expression with an increase in methylation in gestational day 17, supported findings from our enrichment analysis. Collectively, our results highlight a connection between MIA driven methylation changes during gestation and schizophrenia gene expression signatures in the adult brain. These findings carry important implications for early preventative strategies in schizophrenia.