精神分裂症患者白质微结构异常相关基因

Genes associated with white matter microstructure abnormality in schizophrenia

目的:探究精神分裂症患者平均峰度值(MK)改变,分析基因表达水平与精神分裂症患者脑白质MK改变的相关性,从而探索精神分裂症患者脑白质纤维异常改变的相关基因。方法:本研究共纳入94例精神分裂症患者及91例健康对照者,对所有的受试者进行DKI图像采集,经指标解算获得MK参数图,利用基于全脑体素分析(VBA)方法比较MK的病例-对照组间差异。采用艾伦脑图谱(AHBA)提供的6例捐献者脑组织基因表达数据,提取每个脑组织采样点中精神分裂症风险基因的表达数据。跨脑采样点对MK病例-对照组间差异图和每个基因的表达水平进行空间相关分析,以确定与精神分裂症患者MK显著相关的基因。结果:与健康对照组相比,精神分裂症患者的MK减低主要发生于双侧前额叶白质、放射冠、内囊和胼胝体。发现与MK差异显著相关的基因16个,这些基因主要与钙离子稳态及跨膜转运、三磷酸肌醇代谢过程、细胞间连接有关。结论:本研究提供了一组可能与精神分裂症白质复杂程度改变相关的基因,可作为精神分裂症白质微结构改变的生物学机制研究的候选基因。

Objective: To investigate the mean kurtosis(MK) changes in patients with schizophrenia and to analyze correla-tion of gene expression level with MK in order to explore genes associated with white matter microstructure abnormality in schizophrenia. Methods: Ninety-four schizophrenia patients and 91 healthy controls were recruited to undergo a diffusion kurtosis imaging(DKI). Subsequently, quantitative map of MK for each subject was calculated. MK difference between patients with schizophrenia and healthy controls was compared using voxel-based analysis(VBA). For each brain tissue sample, expression profiles of 196 schizophrenia risk genes were extracted from six donated brains of the Allen Human Brain Atlas(AHBA).Genes associated with MK change in schizophrenia were identified by performing sample-wise spatial correlations between ex-pression levels of each gene and case-control MK difference. Results: Relative to healthy controls, patients with schizophrenia had decreased MK mainly in the white matter of prefrontal lobe, corona radiata, internal capsule and corpus callosum. We found that expression levels of 16 genes had showed significant sample-wise spatial correlations with MK changes in schizophrenia. These genes were functionally enriched for calcium ion homeostasis and transmembrane transport, inositol trisphosphate metabolic process and cell-cell junction. Conclusion: This study provides a set of genes possibly associated with MK change in schizophrenia, which could be used as candidate genes to explore biological mechanisms underlying the struc-tural impairments of white matter in schizophrenia.