Longitudinal multi-omics alterations response to 8-week risperidone monotherapy: Evidence linking cortical thickness, transcriptomics and epigenetics

作者：Xiaofen Zong, Gaohua Wang, Zhaowen Nie, Simeng Ma, Lijun Kang, Nan Zhang, Shenhong Weng, Qing Tan, Junjie Zheng, Maolin Hu · 发表于：Frontiers in Psychiatry · 年份：2023 · DOI：10.3389/fpsyt.2023.1127353 · 被引用次数：8 · 研究领域：Epigenetics and DNA Methylation、Schizophrenia research and treatment、Genetic Associations and Epidemiology

Background Antipsychotic 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. Methods Utilizing 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. Results We 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 linke...