Risperidone-induced changes in DNA methylation in peripheral blood from first-episode schizophrenia patients parallel changes in neuroimaging and cognitive phenotypes
Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved..
BACKGROUND: Second generation antipsychotics such as risperidone are first-line pharmacotherapy treatment choices for schizophrenia. However, our ability to reliably predict and monitor treatment reaction is impeded by the lack of relevant biomarkers. As a biomarker for the susceptibility of schizophrenia and clozapine treatment response, DNA methylation (DNAm) has been studied, but the impact of antipsychotics on DNAm has not been explored in drug-naïve patients.
OBJECTIVE: The aim of the present study was to examine changes of DNAm after short-term antipsychotic therapy in first-episode drug-naïve schizophrenia (FES) to identify the beneficial and adverse effect of risperidone on DNAm and their relation to treatment outcome.
METHODS: Thirty-eight never treated schizophrenia patients and 38 demographically matched individuals (healthy controls) were assessed at baseline and at 8-week follow-up with symptom ratings, and cognitive and functional imaging procedures, at which time a blood draw for DNAm studies was performed. During the 8-week period, patients received treatment with risperidone monotherapy. An independent data set was used as replication.
RESULTS: We identified brain related pathways enriched in 4,888 FES-associated CpG sites relative to controls. Risperidone administration in patients altered DNAm in 5,979 CpG sites relative to baseline. Significant group differences in DNAm at follow-up were seen in FES patients at 6,760 CpG sites versus healthy controls. Through comparison of effect size, we found 87.54% out of the risperidone-associated changes in DNAm showed possible beneficial effect, while only 12.46% showed potential adverse effect. There were 580 DNAm sites in which changes shifted methylation levels to be indistinguishable from controls after risperidone treatment. The DNAm changes of some sites that normalized after treatment were correlated with treatment-related changes in symptom severity, spontaneous neurophysiological activity, and cognition. We replicated our results in an independent data set.
CONCLUSION: The normalizing effect of risperidone monotherapy on gene DNAm, and its correlation with clinically relevant phenotypes, indicates that risperidone therapy is associated with DNAm changes that are related to changes in brain physiology, cognition and symptom severity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:317 |
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| Enthalten in: |
Psychiatry research - 317(2022) vom: 30. Nov., Seite 114789 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hu, Maolin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.11.2022 Date Revised 17.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.psychres.2022.114789 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Hu, Maolin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Risperidone-induced changes in DNA methylation in peripheral blood from first-episode schizophrenia patients parallel changes in neuroimaging and cognitive phenotypes |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 16.11.2022 | ||
| 500 | |a Date Revised 17.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Second generation antipsychotics such as risperidone are first-line pharmacotherapy treatment choices for schizophrenia. However, our ability to reliably predict and monitor treatment reaction is impeded by the lack of relevant biomarkers. As a biomarker for the susceptibility of schizophrenia and clozapine treatment response, DNA methylation (DNAm) has been studied, but the impact of antipsychotics on DNAm has not been explored in drug-naïve patients | ||
| 520 | |a OBJECTIVE: The aim of the present study was to examine changes of DNAm after short-term antipsychotic therapy in first-episode drug-naïve schizophrenia (FES) to identify the beneficial and adverse effect of risperidone on DNAm and their relation to treatment outcome | ||
| 520 | |a METHODS: Thirty-eight never treated schizophrenia patients and 38 demographically matched individuals (healthy controls) were assessed at baseline and at 8-week follow-up with symptom ratings, and cognitive and functional imaging procedures, at which time a blood draw for DNAm studies was performed. During the 8-week period, patients received treatment with risperidone monotherapy. An independent data set was used as replication | ||
| 520 | |a RESULTS: We identified brain related pathways enriched in 4,888 FES-associated CpG sites relative to controls. Risperidone administration in patients altered DNAm in 5,979 CpG sites relative to baseline. Significant group differences in DNAm at follow-up were seen in FES patients at 6,760 CpG sites versus healthy controls. Through comparison of effect size, we found 87.54% out of the risperidone-associated changes in DNAm showed possible beneficial effect, while only 12.46% showed potential adverse effect. There were 580 DNAm sites in which changes shifted methylation levels to be indistinguishable from controls after risperidone treatment. The DNAm changes of some sites that normalized after treatment were correlated with treatment-related changes in symptom severity, spontaneous neurophysiological activity, and cognition. We replicated our results in an independent data set | ||
| 520 | |a CONCLUSION: The normalizing effect of risperidone monotherapy on gene DNAm, and its correlation with clinically relevant phenotypes, indicates that risperidone therapy is associated with DNAm changes that are related to changes in brain physiology, cognition and symptom severity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Biomarker | |
| 650 | 4 | |a DNA methylation | |
| 650 | 4 | |a First-episode schizophrenia | |
| 650 | 4 | |a Risperidone treatment | |
| 650 | 7 | |a Risperidone |2 NLM | |
| 650 | 7 | |a L6UH7ZF8HC |2 NLM | |
| 650 | 7 | |a Antipsychotic Agents |2 NLM | |
| 700 | 1 | |a Xia, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Zong, Xiaofen |e verfasserin |4 aut | |
| 700 | 1 | |a Sweeney, John A |e verfasserin |4 aut | |
| 700 | 1 | |a Bishop, Jeffrey R |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Yanhui |e verfasserin |4 aut | |
| 700 | 1 | |a Giase, Gina |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Bingshan |e verfasserin |4 aut | |
| 700 | 1 | |a Rubin, Leah H |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yunpeng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zongchang |e verfasserin |4 aut | |
| 700 | 1 | |a He, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiaogang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Chunyu |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Jinsong |e verfasserin |4 aut | |
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