重性精神障碍谷氨酸能系统相关基因的分子遗传学及功能影像学研究
发布时间：2019-01-21 14:21
【摘要】：研究背景： 精神分裂症和重性抑郁障碍(Major Depression, MDD)是两种常见的重性精神障碍。大量的研究表明遗传因素在其发病中起到重要的作用,识别重性精神障碍的易感基因是当前该研究领域的关键问题之一。越来越多的研究表明谷氨酸能系统在重性精神障碍的发生中起到重要的作用。 由于临床症状复杂,存在多个微效基因及基因—环境的相互作用,目前重性精神障碍的遗传学研究普遍存在结果的重复性较差的问题。内表型概念的引入,降低了表型多样性困扰,促进其易感基因的发现。研究表明通过功能磁共振成像(functional Magnetic Resonance Imaging, fMRI)发现的脑影像学改变是重性精神障碍可靠的内表型。 目的： 寻找精神分裂症及MDD特异的脑影像学改变；验证谷氨酸能系统相关基因与精神分裂症及MDD疾病易感性及其脑影像学改变的相关性。 研究内容：本研究主要开展了以下三方面的内容： 1、应用“病例-对照”关联研究的方法分析了14个谷氨酸能系统相关基因的43个SNPs位点与精神分裂症及MDD的相关性。首先在96例对照及96例精神分裂症样本中对所选SNPs位点进行初筛,然后分别在480例对照、454例精神分裂症患者及488例MDD患者中对初筛得到的阳性易感基因进行验证。 2、精神分裂症及MDD的fMRI研究。 分别收集精神分裂症患者、MDD患者及对照被试共三组被试静息及任务态fMRI扫描数据。对静息态数据,研究局部一致性(Regional Homogeneity, ReHo)及默认网络(Default Mode Network, DMN)的差异；在任务态fMRI的研究中,采用n-back范式研究三组被试工作记忆行为学及脑影像学改变的差异。 3、谷氨酸能系统相关基因在精神分裂症及MDD患者脑影像学改变中的作用。 在前两部分工作上的基础上,以关联分析中得到的阳性位点为分组标准,根据基因分型结果将三组被试分为不同的亚组,在不同的亚组之间研究其脑影像学的差异,探索阳性易感基因对患者脑影像学改变的作用及其作用模式。 结果： 1、关联分析表明D-型氨基酸氧化酶激活剂(D-Amino acid Oxidase Activator, DAOA)基因与精神分裂症及MDD相关。其中rs2391191(M15)、rs3918341(M16)、rs778294(M19)三点及M15的基因型分布在MDD患者及对照中出现明显的差异。多个两点及三位点组成的单倍型与精神分裂症及MDD的疾病易感性显著相关。 2、(1)与对照组相比,精神分裂症患者组右侧额上回ReHo升高,左侧颞上回ReHo降低,额上回存在着ReHo值左侧小于右侧的现象； (2)在DMN分析中发现,与对照组相比,精神分裂症患者组在双侧枕中回活动增强,而MDD患者组在左侧额下回、岛叶及右侧额中回活动减弱； (3)精神分裂症患者组与对照组n-back实验的行为学表现存在显著差异,但未发现两组存在活动显著差异的脑区； (4)静息状态下,精神分裂症患者组相对于对照组在楔叶、海马、枕下回和颞中回的中间度(Betweenness)出现显著差异；而在2-back任务状态下,患者功能连接的数目减少,楔叶、枕中回及顶上回的中间度异常。 3、根据SNP rs2391191(M15)位点将被试分为AA基因型组及G+基因型组。结果显示在MDD患者的右侧小脑蚓部山顶及额中回、精神分裂症患者的左侧豆状核存在M15位点的基因型主效应,而在MDD患者左侧小脑蚓垂区及左侧颞中回、精神分裂症患者左侧楔叶存在基因型与疾病状态的交互作用。 结论： 谷氨酸能系统可能在精神分裂症及MDD的发病及其特异的脑影像学改变中发挥重要作用。相同易感基因(DAOA基因)通过不同位点或位点的组合与精神分裂症及MDD的疾病易感性相关,并导致不同精神障碍患者脑影像学出现特异的改变。
[Abstract]:Study Background: Schizophrenia and heavy depressive disorder (MDD) are two common heavy mental barriers A large number of studies have shown that the genetic factors play an important role in the pathogenesis of the disease, and the sensitive gene for identifying the heavy mental disorder is the key problem in the current research field. One. More and more studies have shown that the glutamate energy system plays an important role in the occurrence of heavy mental disorders. Because of the complex clinical symptoms, there are multiple micro-effect genes and the interaction between the gene and the environment, and the genetic research of the current heavy mental disorder has a poor repeatability. The introduction of the concept of the internal phenotype reduces the problem of phenotypic diversity and promotes its susceptibility to gene expression. The findings of the study show that the brain imaging changes found by functional magnetic resonance imaging (fMRI) are reliable for heavy mental disorders. internal phenotype Objective: To find the brain imaging changes of schizophrenia and MDD, and to verify the susceptibility of the related genes to the system related to the treatment of schizophrenia and MDD and their brain images. The relevance of study change. Research content: the main development of this study The contents of the following three aspects are: 1. Analysis of 43 SNPs site and spirit of 14 glutamic acid energy system related genes by using the method of 鈥淐ase-Control鈥，
本文编号：2412736
[Abstract]:Study Background: Schizophrenia and heavy depressive disorder (MDD) are two common heavy mental barriers A large number of studies have shown that the genetic factors play an important role in the pathogenesis of the disease, and the sensitive gene for identifying the heavy mental disorder is the key problem in the current research field. One. More and more studies have shown that the glutamate energy system plays an important role in the occurrence of heavy mental disorders. Because of the complex clinical symptoms, there are multiple micro-effect genes and the interaction between the gene and the environment, and the genetic research of the current heavy mental disorder has a poor repeatability. The introduction of the concept of the internal phenotype reduces the problem of phenotypic diversity and promotes its susceptibility to gene expression. The findings of the study show that the brain imaging changes found by functional magnetic resonance imaging (fMRI) are reliable for heavy mental disorders. internal phenotype Objective: To find the brain imaging changes of schizophrenia and MDD, and to verify the susceptibility of the related genes to the system related to the treatment of schizophrenia and MDD and their brain images. The relevance of study change. Research content: the main development of this study The contents of the following three aspects are: 1. Analysis of 43 SNPs site and spirit of 14 glutamic acid energy system related genes by using the method of 鈥淐ase-Control鈥，
本文编号：2412736
本文链接：https://www.wllwen.com/yixuelunwen/jsb/2412736.html
最近更新
教材专著
