NEUROMORPHOMETRY IN SIBLINGS AT RISK FOR SCHIZOPHRENIA

精神分裂症的神经解剖异常可能与遗传因素、环境因素或它们之间的相互作用有关。因此，对临床、神经形态和遗传因素不同的兄弟姐妹进行的神经成像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。如果涉及精神分裂症发病机制的神经发育异常背后有特定的基因，那么可以通过检查精神分裂症先证者及其兄弟姐妹中这些基因与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，允许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体和丘脑的结构，在这些研究中，形状畸形被发现有助于区分不同的组。除了这些结构，我们现在已经开始评估大脑皮质的特定区域(即扣带回、额上回、额中回和额下回，以及舌上回)。由于其精确度，用于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。本项目的具体目标是：目标1.收集高 目的2.验证脑结构体积、厚度、形状和对称性的测量可以区分精神分裂症先证组、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.估计选定的脑结构测量在精神分裂症和对照同胞对中的遗传度；目的4.收集所有受试者的纵向数据，并初步检验神经形态计量学测量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展为精神病理学。

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.