Methylation Analysis in Treatment-Resistant Schizophrenia
Kikuchi, Masataka Osaka University
Nakazawa, Takanobu Tokyo University of Agriculture
Kinoshita, Makoto Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Yamamori, Hidenaga National Institute of Mental Health|Osaka University|Japan Community Health Care Organization Osaka Hospital
Yasuda, Yuka National Institute of Mental Health|Medical Corporation Foster
Fujimoto, Michiko National Institute of Mental Health|Osaka University
Hashimoto, Ryota National Institute of Mental Health
Schizophrenia is a mental illness that involves both genetic and environmental factors. Clozapine, an atypical antipsychotic, is a well-established therapy for treatment-resistant schizophrenia. In this study, we focused on a set of monozygotic twins with treatment-resistant schizophrenia in which one twin effectively responded to clozapine treatment and the other did not. Our previous study generated neurons from induced pluripotent stem (iPS) cells derived from these patients and compared the transcriptome profiles between mock- and clozapine-treated neurons. In this study, we performed genome-wide DNA methylation profiling to investigate the mechanisms underlying gene expression changes. First, we extracted the differentially methylated sites from each twin based on statistical analysis. Then, we combined the DNA methylation profiling with transcriptome profiling from our previous RNA-seq data. Among the genes with altered methylation and expression, we found the different proportions of the genes related to neuronal and synaptic functions between the clozapine responder and non-responder (35.7 and 6.7%, respectively). This trend was observed even when the basal differences between the responder and non-responder was excluded. These results suggest that effective clozapine action may correct the abnormalities of neuronal and synapse functions in schizophrenia via changes in methylation.
Frontiers in Psychiatry
Frontiers Media S.A.
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