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Methylation Analysis in Monozygotic Twins With Treatment-Resistant Schizophrenia and Discordant Responses to Clozapine

Bibliographic Data

ID15526775
AuthorsMasataka Kikuchi (0000-0002-9562-841X, The University of Osaka), Takanobu Nakazawa (0000-0003-4863-1277, Tokyo University of Agriculture), Makoto Kinoshita (0000-0003-2780-5776, Tokushima University), Hidenaga Yamamori (0000-0003-2100-1881, The University of Osaka), Yuka Yasuda (0000-0002-2746-1590, National Institute of Mental Health), Michiko Fujimoto (0000-0002-9482-2456, The University of Osaka), Ryota Hashimoto (0000-0002-5941-4238, National Institute of Mental Health), Shusuke Numata (0009-0009-0697-8871, Tokushima University, corresponding author)
Year2021
Volume12
Pages734606-734606
Publication date2021-09-20
Open AccessYes
TypeARTICLE
VenueFrontiers in Psychiatry (JOURNAL)
Journal identifiersISSN: 1664-0640 • E-ISSN: 1664-0640
PublisherFrontiers Media (PUBLISHER • CH)
DOI10.3389/fpsyt.2021.734606
PMID34616320
OpenAlexW3200101885
LanguageEN
Citations received1
References cited35

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

Bioinformatics · Biology · Clozapine · DNA methylation · Gene · Gene expression · Gene expression profiling · Methylation · Psychiatry · Schizophrenia (object-oriented programming · Transcriptome · Congenital heart defects research · Epigenetics and DNA Methylation · Genetics and Neurodevelopmental Disorders · Medicine · Genetics

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Citations per year1
Citation span2026 - 2026 (1)
Highly citedNo

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