精神分裂症脑结构和功能特征的双生子磁共振成像研究

精神分裂症(SCH)是一种常见的复杂疾病，由多个微效基因协同并与环境因素共同作用所致。既往研究提示，SCH患者的脑结构和功能特征有较高遗传度，同时也受到环境因素的影响，其发生机制可能分别与遗传多态性和表观遗传修饰有关。本项目计划在扩大现有样本数据的基础上，建立SCH双生子影像资源库，深入分析多模态磁共振成像数据，探索SCH脑结构和功能特征；利用共同患病/单一患病、同卵/异卵双生子数据，建立SCH脑结构和功能特征指标的相关遗传模型和结构方程，量化评估上述影像特征的遗传和环境效应，即加性遗传效应、同胞共享环境效应及个体特殊环境效应；继而通过候选基因多态性和DNA甲基化检测，在分子水平上分别验证SCH脑影像特征的遗传和环境效应。项目预期结果有助于了解遗传和环境效应与SCH脑影像特征之间的关系，为确定SCH内表型、减少疾病异质性，以及SCH从表型到分子机制的研究提供线索依据。

Schizophrenia has a clear genetic predisposition and complex disease clinical phenotype. It is caused by the interaction between multiple genes of minor pathogenic effect and environmental risk factors. Determining effective endophenotypes of schizophrenia will help to reduce the heterogeneity of disease and to improve the statistical power of genetic studies. Given the neurodevelopmental abnormalities of schizophrenia and its potential relationship with genetic and environmental risk factors, it is important to find the genetic and environmental determinants of the schizophrenia associated brain structural and functional features, and determine some effective brain imaging endophenotypes of schizophrenia. Twins are excellent materials to distinguish the difference effects of genetic and environmental factors on human individual traits. The plan of the current project is to 1) build a schizophrenia twins and relatives magnetic resonance imaging (MRI) database, recruiting concordant/disconcordant schizophrenia twins and its co-twins and controls twins (including monozygotic and dizygotic twins); 2) investigate the schizophrenia associated brain structural and functional abnormalities, by using the multi-model MRI data and the latest analysis tools and methods; explore the genetic and environmental determinants of the association between brain abnormalities and schizophrenia, by using the Mx Statistical Modeling for maximum likelihood genetic model fitting to directly estimate model parameters from the concordant/disconcordant monozygotic and dizygotic twins data; 3) examine the correlation of the genetic polymorphism and promoter methylation of the candidate genes with the schizophrenia associated abnormalities due to the genetic or environmental factors. The expected results of this project will help to understand the relationship between genetic and environmental factors and schizophrenia associated brain features, and facilitates the genetic study of schizophrenia by providing effective endophenotypes. And the findings of the pilot study on molecular mechanism of schizophrenia associated abnormalities due to different genetic or environmental factors will provide new clues to the etiology research of schizophrenia.