NEUROMORPHOMETRY IN SIBLINGS AT RISK FOR SCHIZOPHRENIA

对有精神分裂症风险的兄弟姐妹进行神经形态测量

• 批准号: 7476360
• 负责人: JOHN G CSERNANSKY
• 金额: $ 32.39万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7476360
• 关键词: Age; Anatomy; Automation; Brain; Cerebral cortex; Clinical; Cognitive; Communities; Complex; Data; Data Set; Databases; Deformity; Development; Disease; Electrodes; Environmental Risk Factor; Genes; Genetic; Heritability; Hippocampus (Brain); Human; Image; Inbred Mouse; Individual; Inferior frontal gyrus; Laboratories; Location; Macaca; Measurement; Measures; Mental disorders; Methods; Neurosciences; Pathogenesis; Phenotype; Psychopathology; Recombinants; Relative (related person); Research Infrastructure; Research Personnel; Resolution; Resources; Risk; Scanning; Schizophrenia; Shapes; Short-Term Memory; Siblings; Structure; Testing; Thalamic structure; Thick; Validation; Variant; cingulate gyrus; computerized tools; concept; mecarzole; neuroimaging; proband; tool

Neuroanatomical abnormalities in schizophrenia may be attributable to genetic factors, environmental factors, or their interaction. Thus, neuroimaging studies of sibling pairs that vary in clinical, neuromorphological and genetic factors provide a powerful approach to evaluating brain structure abnormalities associated with schizophrenia. If specific genes underlie neurodevelopmental abnormalities involved in the pathogenesis of schizophrenia, such genes could be discovered by examining the degree to which they segregate with brain structure abnormalities in schizophrenia probands and their siblings. Recently, we have developed computational tools for the analysis of brain structure that permit the detailed analysis of brain structure volumes and shapes. We have used these to compare the structure of the hippocampus and thalamus in schizophrenia subjects and matched controls, and in these studies, shape deformities were found to help discriminate between groups. In addition to these structures, we have now begun the assessement of specific regions of the cerebral cortex (i.e., cingulate gyrus, superior, middle and inferior frontal gyrus, and superior lingual gyrus). Because of their precision, computational tools for brain structure analysis should be an ideal method for discovering subtle abnormalities of brain structure in the nonpsychotic siblings of schizophrenia subjects. The specific aims of this Project are: Aim 1. To collect high resolution MR scans from 50 schizophrenia probands and 50 of their non-psychotic siblings who are within the age of risk for developing the disorder, and from 50 control subjects and 50 of their siblings; Aim 2. To test the hypothesis that measures of brain structure volume, thickness, shape and symmetry can discriminate groups of schizophrenia probands, the siblings of schizophrenia probands, control subjects and the siblings of control subjects; Aim 3. To estimate the heritability of the selected brain structure measures in both schizophrenia and control sibling pairs; Aim 4. To collect longitudinal data in all subjects, and to preliminarily test the hypothesis that neuromorphometric measures can be used to discriminate between siblings of schizophrenia probands that do and do not develop psychopathology during the period of study.

精神分裂症的神经解剖学异常可能归因于遗传因素、环境因素或它们的相互作用。因此，对临床、神经形态和遗传因素不同的兄弟姐妹进行神经影像学研究，为评估与精神分裂症相关的大脑结构异常提供了一种强有力的方法。如果特定基因是精神分裂症发病机制中涉及的神经发育异常的基础，那么可以通过检查这些基因与精神分裂症先证者及其兄弟姐妹的大脑结构异常的分离程度来发现这些基因。 最近，我们开发了用于分析大脑结构的计算工具，可以详细分析大脑结构的体积和形状。我们用这些来比较精神分裂症受试者和匹配对照组的海马和丘脑结构，在这些研究中，发现形状畸形有助于区分群体。除了这些结构之外，我们现在还开始评估大脑皮层的特定区域（即扣带回、额上回、额中回和下回以及舌上回）。由于其精确性，用于大脑结构分析的计算工具应该是发现非精神病患者大脑结构细微异常的理想方法。 精神分裂症受试者的兄弟姐妹。该项目的具体目标是： 目标 1. 收集高 对 50 名精神分裂症先证者和 50 名处于患该疾病风险年龄的非精神病兄弟姐妹以及 50 名对照受试者和 50 名兄弟姐妹进行的高分辨率 MR 扫描；目标 2. 检验大脑结构体积、厚度、形状和对称性的测量可以区分精神分裂症先证者群体、精神分裂症先证者的兄弟姐妹、对照受试者和对照受试者的兄弟姐妹的假设；目标 3. 估计精神分裂症患者和对照兄弟姐妹对中选定的大脑结构测量的遗传力；目标 4. 收集所有受试者的纵向数据，并初步检验神经形态计量学测量可用于区分在研究期间出现和未出现精神病理学的精神分裂症先证者的兄弟姐妹的假设。