脑源性神经营养因子Val66Met基因多态性与中国汉族精神分裂症认知功能的相关性研究

发布时间：2018-03-17 21:17

本文选题：BDNFVal66Met　切入点：认知功能　出处：《山东大学》2013年硕士论文　论文类型：学位论文

【摘要】：目的认知功能损害是精神分裂症的核心症状之一,与精神分裂症患者社会功能的恢复及长期预后密切相关。脑源性神经营养因子(Brain-derived neurotrophic factor,BDNF)Val66Met基因多态性可能参与精神分裂症发病机制,既往研究提示BDNFMet基因变异与大脑海马、额叶、皮质等脑结构变化有关,会引起学习、记忆等认知功能的改变。本研究以中国汉族住院精神分裂症患者和正常健康人群为研究对象,探讨BDNFVal66Met基因多态性与精神分裂症认知功能的相关性。方法本研究为病例对照研究,以400例中国汉族住院精神分裂症患者和483例正常健康人群为研究对象,采用自编一般人口学资料调查表收集精神分裂症患者和健康对照的一般人口学资料,中文版精神分裂症认知功能成套测验(Matrics Consensus Cognitive Battery, MCCB)、威斯康星卡片分类测验(Wisconsin Card Sorting Test, WCST)、Stroop测验(Stroop Color Word Test)、代币运动对精神分裂症患者进行认知功能评估,用阳性与阴性症状量表(Positive and Negative Syndrome Scale, PANSS)评估精神分裂症患者的精神病性症状。在清晨7点收集研究对象的空腹肘静脉血5ml,置于含有10%的EDTAK防凝试管中混匀,3000转／分离心,10分钟后收集白细胞层,保存于-70℃冰箱待测。应用改良碘化钾的方法提取外周血DNA,采用实时定量PCR Taqman探针法检测研究对象的BDNF Val66Met基因型。用SPSS19.0统计软件进行统计分析,采用卡方检验比较住院精神分裂症患者与正常对照组基因型频率与等位基因频率差异是否有统计学意义,使用单因素方差分析和非参数检验比较不同基因型(BDNFVal/Val、 BDNFVal/Met、BDNFMet/Met)精神分裂症患者之间一般人口学资料及临床精神病性症状,使用协方差分析和非参数检验比较不同基因型精神分裂症患者认知功能差异。结果 1.400例住院精神分裂症患者和483例正常健康对照比较BDNFVa166Met基因型频率与等位基因频率的差异有统计学意义,住院精神分裂症患者组BDNFMet/Met基因型的分布频率(31.54%)、Met等位基因的频率(56%)均高于正常对照组(24.0%、49%),提示Met基因可能为精神分裂症的易感基因。 2.不同基因型精神分裂症患者在MCCB中的工作记忆、处理速度维度受损程度有统计学差异,其中,BDNFMet/Met基因型者其工作记忆维度受损较BDNFVal/Val基因型更为严重：BDNFMet/Met基因型者其处理速度维度较BDNFVal/Val、BDNFVal/Met基因型受损严重。结论 1. BDNFVa166Met基因多态性可能参与了精神分裂症的发病机制,Met等位基因变异可能是精神分裂症发病的危险因素。 2. BDNFMet/Met基因型可能是精神分裂症认知功能障碍的危险因素之一。
[Abstract]:Purpose. Cognitive impairment is one of the core symptoms of schizophrenia, which is closely related to the recovery of social function and long-term prognosis of schizophrenic patients. Brain-derived neurotrophic factor-BDNFVal66Met gene polymorphism may be involved in the pathogenesis of schizophrenia. Previous studies have shown that BDNFMet gene mutations are associated with changes in brain structures such as the hippocampus, frontal lobe, cortex, and so on, which may lead to learning. The purpose of this study was to investigate the relationship between BDNFVal66Met gene polymorphism and cognitive function in Chinese Han patients with schizophrenia and normal controls. Method. In this study, 400 Chinese Han inpatients with schizophrenia and 483 healthy people were selected as case-control study subjects. General demographic data of schizophrenic patients and healthy controls were collected by self-compiled general demographic information questionnaire. Matrics Consensus Cognitive Battery. MCCBX, Wisconsin Card Sorting Test, WCSTT Stroop Test Stroop Color Word Test, token exercise were used to evaluate the cognitive function of schizophrenic patients. Positive and Negative Syndrome scale (PANSSs) was used to evaluate psychotic symptoms in schizophrenic patients. Fasting elbow venous blood was collected at 7 a.m. and placed in a 10% EDTAK anticoagulant test tube. After 10 minutes of centrifugation, the white blood cells were collected, The peripheral blood DNA was extracted by modified potassium iodide method, and the BDNF Val66Met genotypes of the subjects were detected by real-time quantitative PCR Taqman probe method. The BDNF Val66Met genotypes were analyzed by SPSS19.0 software. The difference of genotype frequency and allele frequency between inpatients with schizophrenia and normal controls was statistically significant by chi-square test. Univariate ANOVA and nonparametric tests were used to compare the general demographic data and clinical psychotic symptoms among patients with schizophrenia with different genotypes of BDNFVal-P value, BDNFVal-Meta-Meta-Meta. Covariance analysis and non-parametric test were used to compare the cognitive function of patients with different genotypes of schizophrenia. Results. 1.The frequencies of BDNFVa166Met genotypes and alleles were significantly different in 400 inpatients with schizophrenia and 483 healthy controls. The distribution frequency of BDNFMet/Met genotype in the inpatients with schizophrenia was higher than that in the normal control group. The allele frequency of Met allele was higher than that of the normal control group. It suggested that the Met gene might be a susceptible gene for schizophrenia. 2. The working memory and processing speed of patients with different genotypes of schizophrenia were significantly different in MCCB. The working memory dimension of BDNF Met-Met genotype was more serious than that of BDNFVal/Val genotype. The processing speed dimension of BDNF Met-Met genotype was more serious than that of BDNFValp value / Met genotype. Conclusion. 1. The polymorphism of BDNFVa166Met gene may be involved in the pathogenesis of schizophrenia. 2. BDNFMet/Met genotype may be one of the risk factors for cognitive dysfunction in schizophrenia.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.3

【共引文献】