PSYCH OpenIR  > 健康与遗传心理学研究室
精神分离正谱系神经软体征遗传性研究
其他题名The heritability of neurological soft signs in schizophrenia spectrum disorders
徐婷
学位类型博士
导师陈楚侨
2012-05
学位授予单位中国科学院研究生院
学位授予地点北京
学位专业心理学
关键词神经软体征 精神分裂症 内表型 遗传度
摘要神经软体症状(Neurological Soft Signs)是一种常见于精神分裂症病人及其直系家属的细微的神经异常。元分析的结果表明,神经软体征在病人未患病的一级家属中的得分介于病人与健康对照组之间。并且,研究表明神经软体征与药物治疗没有显著相关,具有一定的稳定性。因此我们推测神经软体征有可能是精神分裂症的一种内表型。然而,目前对神经软体征遗传性的研究十分缺乏,相关脑结构与脑功能的遗传性研究还没有。因此,我们从行为、脑结构、脑功能三方面系统地考察神经软体征的遗传性,为神经软体征是否是精神分裂症内表型提供证据支持。 研究一测量了75对精神分裂症病人与其未患病的一级家属的神经软体征,并计算了总分、各个分量表分与各个子项目分上精神分裂症病人与其一级家属之间的相关关系,结果表明神经软体征在病人与家属之间有显著的相关关系,r=0.388,p<0.001。 研究二收集391对健康的青少年双生子数据,分别计算同卵双生子、异卵双生子中的组内相关系数ICC (Intraclass Correlation),并利用经典的Falconer遗传度公式与结构方程模型计算神经软体征的行为遗传度。结果表明,神经软体征在同卵双生子中的ICC要高于异卵双生子的ICC,神经软体征的行为遗传度在0.21-0.59之间。 研究三使用VBM (Voxel-Based Morphometry)对54对健康双生子的脑结构进行分析,考察神经软体征总分、分量表分与灰质密度的相关脑区,并且利用结构方程模型,计算了基于voxel的灰质密度的遗传程度。结果表明,神经软体征与大脑的皮层结构,丘脑、小脑部分的灰质密度呈负相关,在这些相关区域中,丘脑与小脑部分的灰质密度是可以遗传的,为神经软体征的遗传性提供了脑结构的证据支持。 研究四收集了54对健康双生子,使用Fist-Edge-Palm子项目的类似范式探讨运动协调的神经软体征任务下的脑激活模式,并选取感觉运动区作为种子点进行了PPI (Psychophysiological interaction)分析。利用结构方程模型,计算FEP任务的脑激活与PPI功能连接的遗传程度。结果表明,FEP比拍掌任务激活了更广泛的中央前回、中央后回与感觉运动区,并且FEP的激活在部分脑区是可以遗传的。PPI功能连接的结果中并没未显示出显著的遗传度。 四个研究分别从行为上、脑结构、脑功能系统地提供了神经软体征可以遗传的证据,支持了神经软体征是精神分裂症潜在内表型的观点。
其他摘要Neurological Soft Signs (NSS) are minor neurological abnormalities which are more prevalent in schizophrenia as well as their non-psychotic relatives, when compared with healthy controls. Results of a meta-analysis demonstrated that NSS in relatives were in between those of patients with schizophrenia and healthy controls. Moreover, majority of studies reported non-significant results in treatment of NSS, which implies that NSS is fairly stable in schizophrenia. These evidences suggested that NSS may represent a putative endophenotype for schizophrenia. However, few studies have investigated the heritability of NSS, let alone heritability of structural and functional imaging of NSS. Accordingly, to explore whether NSS are endophenotype for schizophrenia, we attempted to systematically estimate the heritability of NSS from three aspects: behavioral, brain structure and brain function. In the first study, we assessed 75 pairs of schizophrenia patients and their non-psychotic first-degree relatives and then calculated the correlations between patients and relatives in NSS total and sub-scale scores. The results demonstrated that the correlations between patients and relatives are significant with r=0.388, p<0.01. In the second study, we investigated whether the NSS is heritable in 391 pairs of healthy twins using Falconer’s Formula and Structure Equation Modeling (SEM). The results showed that intraclass correlations (ICC) in monozygotic twins are higher than those in dizygotic twins. The heritability in NSS ranged from 0.21 to 0.59. In the third study, we used VBM (Voxel-Based Morphometry) analysis to investigate the correlations between NSS scores and gray matter density. SEM was employed to determine whether these relevant brain regions are heritable. The results revealed that higher scores of NSS were associated with reduction of gray matter density of certain cerebral cortices, thalamus, and part of cerebellum. Moreover, gray matter density in thalamus and cerebellum were found to be heritable. In the fourth study, a typical NSS item, Fist-Edge-Palm, was chosen to identify brain functional activation specifically related to motor coordination by using block-design fMRI. The psychophysiological interaction (PPI) analysis was performed to evaluate function connectivity change between the seed (sensorimotor cortex) and other brain region during the FEP task relative to the simple Palm Tapping (PT) task. The genetic contribution of each voxel in brain activation and PPI connectivity were calculated. The FEP task displayed hyperactivation in the precentral, postcentral, sensorimontor areas compare to the PT task. Furthermore, pattern of task-related brain activations in the FEP task were found to be heritable in these areas. However, the PPI connectivity change did not show any significant heritability. These findings, based on behavioral, brain structural and brain functional evidences, support the hypothesis that NSS is a potential endophenotype of schizophrenia.
学科领域认知神经科学
语种中文
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/20426
专题健康与遗传心理学研究室
作者单位中国科学院心理研究所
推荐引用方式
GB/T 7714
徐婷. 精神分离正谱系神经软体征遗传性研究[D]. 北京. 中国科学院研究生院,2012.
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