Longitudinal multi-omics alterations response to 8-week risperidone monotherapy: Evidence linking cortical thickness, transcriptomics and epigenetics
BackgroundAntipsychotic treatment-related alterations of cortical thickness (CT) and clinical symptoms have been previously corroborated, but less is known about whether the changes are driven by gene expression and epigenetic modifications.MethodsUtilizing a prospective design, we recruited 42 trea...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1127353/full |
| _version_ | 1811161607652245504 |
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| author | Xiaofen Zong Gaohua Wang Zhaowen Nie Simeng Ma Lijun Kang Nan Zhang Shenhong Weng Qing Tan Qing Tan Junjie Zheng Junjie Zheng Maolin Hu Maolin Hu Maolin Hu |
| author_facet | Xiaofen Zong Gaohua Wang Zhaowen Nie Simeng Ma Lijun Kang Nan Zhang Shenhong Weng Qing Tan Qing Tan Junjie Zheng Junjie Zheng Maolin Hu Maolin Hu Maolin Hu |
| author_sort | Xiaofen Zong |
| collection | DOAJ |
| description | BackgroundAntipsychotic treatment-related alterations of cortical thickness (CT) and clinical symptoms have been previously corroborated, but less is known about whether the changes are driven by gene expression and epigenetic modifications.MethodsUtilizing a prospective design, we recruited 42 treatment-naive first-episode schizophrenia patients (FESP) and 38 healthy controls. Patients were scanned by TI weighted imaging before and after 8-week risperidone monotherapy. CT estimation was automatically performed with the FreeSurfer software package. Participants' peripheral blood genomic DNA methylation (DNAm) status, quantified by using Infinium® Human Methylation 450K BeadChip, was examined in parallel with T1 scanning. In total, CT measures from 118 subjects and genomic DNAm status from 114 subjects were finally collected. Partial least squares (PLS) regression was used to detect the spatial associations between longitudinal CT variations after treatment and cortical transcriptomic data acquired from the Allen Human Brain Atlas. Canonical correlation analysis (CCA) was then performed to identify multivariate associations between DNAm of PLS1 genes and patients' clinical improvement.ResultsWe detected the significant PLS1 component (2,098 genes) related to longitudinal alterations of CT, and the PLS1 genes were significantly enriched in neurobiological processes, and dopaminergic- and cancer-related pathways. Combining Laplacian score and CCA analysis, we further linked DNAm of 33 representative genes from the 2,098 PLS1 genes with patients' reduction rate of clinical symptoms.ConclusionsThis study firstly revealed that changes of CT and clinical behaviors after treatment may be transcriptionally and epigenetically underlied. We define a “three-step” roadmap which represents a vital step toward the exploration of treatment- and treatment response-related biomarkers on the basis of multiple omics rather than a single omics type as a strategy for advancing precise care. |
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| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-04-10T06:17:08Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Psychiatry |
| spelling | doaj.art-3e71da3e047147d7a1ca5165accd3c5c2023-03-02T06:25:45ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402023-03-011410.3389/fpsyt.2023.11273531127353Longitudinal multi-omics alterations response to 8-week risperidone monotherapy: Evidence linking cortical thickness, transcriptomics and epigeneticsXiaofen Zong0Gaohua Wang1Zhaowen Nie2Simeng Ma3Lijun Kang4Nan Zhang5Shenhong Weng6Qing Tan7Qing Tan8Junjie Zheng9Junjie Zheng10Maolin Hu11Maolin Hu12Maolin Hu13Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaSchool of Mathematics and Statistics, Wuhan University, Wuhan, Hubei, ChinaHubei Key Laboratory of Computational Science, Wuhan University, Wuhan, Hubei, ChinaThe Early Intervention Unit, Department of Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, ChinaThe Functional Brain Imaging Institute, Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, ChinaDepartment of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, ChinaBackgroundAntipsychotic treatment-related alterations of cortical thickness (CT) and clinical symptoms have been previously corroborated, but less is known about whether the changes are driven by gene expression and epigenetic modifications.MethodsUtilizing a prospective design, we recruited 42 treatment-naive first-episode schizophrenia patients (FESP) and 38 healthy controls. Patients were scanned by TI weighted imaging before and after 8-week risperidone monotherapy. CT estimation was automatically performed with the FreeSurfer software package. Participants' peripheral blood genomic DNA methylation (DNAm) status, quantified by using Infinium® Human Methylation 450K BeadChip, was examined in parallel with T1 scanning. In total, CT measures from 118 subjects and genomic DNAm status from 114 subjects were finally collected. Partial least squares (PLS) regression was used to detect the spatial associations between longitudinal CT variations after treatment and cortical transcriptomic data acquired from the Allen Human Brain Atlas. Canonical correlation analysis (CCA) was then performed to identify multivariate associations between DNAm of PLS1 genes and patients' clinical improvement.ResultsWe detected the significant PLS1 component (2,098 genes) related to longitudinal alterations of CT, and the PLS1 genes were significantly enriched in neurobiological processes, and dopaminergic- and cancer-related pathways. Combining Laplacian score and CCA analysis, we further linked DNAm of 33 representative genes from the 2,098 PLS1 genes with patients' reduction rate of clinical symptoms.ConclusionsThis study firstly revealed that changes of CT and clinical behaviors after treatment may be transcriptionally and epigenetically underlied. We define a “three-step” roadmap which represents a vital step toward the exploration of treatment- and treatment response-related biomarkers on the basis of multiple omics rather than a single omics type as a strategy for advancing precise care.https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1127353/fullAllen Human Brain Atlasrisperidoneschizophreniamagnetic resonance imagingcortical thicknessDNA methylation |
| spellingShingle | Xiaofen Zong Gaohua Wang Zhaowen Nie Simeng Ma Lijun Kang Nan Zhang Shenhong Weng Qing Tan Qing Tan Junjie Zheng Junjie Zheng Maolin Hu Maolin Hu Maolin Hu Longitudinal multi-omics alterations response to 8-week risperidone monotherapy: Evidence linking cortical thickness, transcriptomics and epigenetics Frontiers in Psychiatry Allen Human Brain Atlas risperidone schizophrenia magnetic resonance imaging cortical thickness DNA methylation |
| title | Longitudinal multi-omics alterations response to 8-week risperidone monotherapy: Evidence linking cortical thickness, transcriptomics and epigenetics |
| title_full | Longitudinal multi-omics alterations response to 8-week risperidone monotherapy: Evidence linking cortical thickness, transcriptomics and epigenetics |
| title_fullStr | Longitudinal multi-omics alterations response to 8-week risperidone monotherapy: Evidence linking cortical thickness, transcriptomics and epigenetics |
| title_full_unstemmed | Longitudinal multi-omics alterations response to 8-week risperidone monotherapy: Evidence linking cortical thickness, transcriptomics and epigenetics |
| title_short | Longitudinal multi-omics alterations response to 8-week risperidone monotherapy: Evidence linking cortical thickness, transcriptomics and epigenetics |
| title_sort | longitudinal multi omics alterations response to 8 week risperidone monotherapy evidence linking cortical thickness transcriptomics and epigenetics |
| topic | Allen Human Brain Atlas risperidone schizophrenia magnetic resonance imaging cortical thickness DNA methylation |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1127353/full |
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