Methylation Analysis in Monozygotic Twins With Treatment-Resistant Schizophrenia and Discordant Responses to Clozapine
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 o...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2021.734606/full |
| _version_ | 1818649988760076288 |
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| author | Masataka Kikuchi Takanobu Nakazawa Makoto Kinoshita Hidenaga Yamamori Hidenaga Yamamori Hidenaga Yamamori Yuka Yasuda Yuka Yasuda Michiko Fujimoto Michiko Fujimoto Ryota Hashimoto Shusuke Numata |
| author_facet | Masataka Kikuchi Takanobu Nakazawa Makoto Kinoshita Hidenaga Yamamori Hidenaga Yamamori Hidenaga Yamamori Yuka Yasuda Yuka Yasuda Michiko Fujimoto Michiko Fujimoto Ryota Hashimoto Shusuke Numata |
| author_sort | Masataka Kikuchi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T01:43:04Z |
| format | Article |
| id | doaj.art-51fb3191b48c4303872bde8b31600046 |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-17T01:43:04Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-51fb3191b48c4303872bde8b316000462022-12-21T22:08:15ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402021-09-011210.3389/fpsyt.2021.734606734606Methylation Analysis in Monozygotic Twins With Treatment-Resistant Schizophrenia and Discordant Responses to ClozapineMasataka Kikuchi0Takanobu Nakazawa1Makoto Kinoshita2Hidenaga Yamamori3Hidenaga Yamamori4Hidenaga Yamamori5Yuka Yasuda6Yuka Yasuda7Michiko Fujimoto8Michiko Fujimoto9Ryota Hashimoto10Shusuke Numata11Department of Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, JapanDepartment of Bioscience, Tokyo University of Agriculture, Tokyo, JapanDepartment of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, JapanDepartment of Pathology of Mental Diseases, National Center of Neurology and Psychiatry, National Institute of Mental Health, Tokyo, JapanDepartment of Psychiatry, Graduate School of Medicine, Osaka University, Osaka, JapanJapan Community Health Care Organization Osaka Hospital, Osaka, JapanDepartment of Pathology of Mental Diseases, National Center of Neurology and Psychiatry, National Institute of Mental Health, Tokyo, JapanMedical Corporation Foster, Osaka, JapanDepartment of Pathology of Mental Diseases, National Center of Neurology and Psychiatry, National Institute of Mental Health, Tokyo, JapanDepartment of Psychiatry, Graduate School of Medicine, Osaka University, Osaka, JapanDepartment of Pathology of Mental Diseases, National Center of Neurology and Psychiatry, National Institute of Mental Health, Tokyo, JapanDepartment of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, JapanSchizophrenia 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.https://www.frontiersin.org/articles/10.3389/fpsyt.2021.734606/fullschizophreniaclozapineDNA methylationmonozygotic twinsiPS cells |
| spellingShingle | Masataka Kikuchi Takanobu Nakazawa Makoto Kinoshita Hidenaga Yamamori Hidenaga Yamamori Hidenaga Yamamori Yuka Yasuda Yuka Yasuda Michiko Fujimoto Michiko Fujimoto Ryota Hashimoto Shusuke Numata Methylation Analysis in Monozygotic Twins With Treatment-Resistant Schizophrenia and Discordant Responses to Clozapine Frontiers in Psychiatry schizophrenia clozapine DNA methylation monozygotic twins iPS cells |
| title | Methylation Analysis in Monozygotic Twins With Treatment-Resistant Schizophrenia and Discordant Responses to Clozapine |
| title_full | Methylation Analysis in Monozygotic Twins With Treatment-Resistant Schizophrenia and Discordant Responses to Clozapine |
| title_fullStr | Methylation Analysis in Monozygotic Twins With Treatment-Resistant Schizophrenia and Discordant Responses to Clozapine |
| title_full_unstemmed | Methylation Analysis in Monozygotic Twins With Treatment-Resistant Schizophrenia and Discordant Responses to Clozapine |
| title_short | Methylation Analysis in Monozygotic Twins With Treatment-Resistant Schizophrenia and Discordant Responses to Clozapine |
| title_sort | methylation analysis in monozygotic twins with treatment resistant schizophrenia and discordant responses to clozapine |
| topic | schizophrenia clozapine DNA methylation monozygotic twins iPS cells |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2021.734606/full |
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