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，神经影像学研究的同胞对不同的临床，神经形态学和遗传因素提供了一个强大的方法来评估与精神分裂症相关的脑结构异常。如果精神分裂症发病机制中神经发育异常的基础是特定的基因，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脑结构异常分离的程度来发现这些基因。 最近，我们已经开发了用于分析大脑结构的计算工具，其允许对大脑结构体积和形状进行详细分析。我们用这些来比较精神分裂症受试者和对照组的海马体和丘脑的结构，在这些研究中，形状变形被发现有助于区分群体。除了这些结构，我们现在已经开始评估大脑皮层的特定区域（即，扣带回、上级、额中回和额下回以及上级舌回）。由于其精确性，脑结构分析的计算工具应该是发现非精神病患者脑结构细微异常的理想方法。 精神分裂症患者的兄弟姐妹该项目的具体目标是：目标1。收集高 来自50名精神分裂症先证者和50名处于发展障碍风险年龄内的非精神病兄弟姐妹以及50名对照受试者和50名他们的兄弟姐妹的分辨率MR扫描;目的2。检验脑结构体积、厚度、形状和对称性的测量可以区分精神分裂症先证者、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;目的3。估计精神分裂症和对照同胞对所选脑结构指标的遗传度;目的4。收集所有受试者的纵向数据，并初步检验神经形态测量方法可用于区分精神分裂症先证者的兄弟姐妹在研究期间是否发生精神病理学的假设。