BRAIN MIDLINE MALFORMATION IN SCHIZOPHRENIA

精神分裂症的脑中线畸形

• 批准号: 6643385
• 负责人: CURTIS KIMBALL DEUTSCH
• 金额: $ 15.3万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-05 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6643385
• 关键词: biomarker; brain; brain disorder diagnosis; brain imaging /visualization /scanning; clinical research; congenital oral /facial /cranial defect; craniofacial; developmental neurobiology; diencephalon; family genetics; human subject; magnetic resonance imaging; mesencephalon; morphology; neuroanatomy; schizophrenia; statistics /biometry

DESCRIPTION: (Verbatim from the Applicant's Abstract): The impetus for this project is an embryological model of brain maldevelopment deriving from our craniofacial dysmorphology studies of schizophrenia. In both an initial study and a recent replication, we have found excessive frontonasal-maxillary junctural dysmorphology among schizophrenic patients and their relatives. How might these findings relate to brain dysmorphogenesis? Because the brain and face arise from shared embryonic origins, genetic deviations or environmental insults during embryogenesis can manifest themselves both in the brain and craniofacial formations. Thus, delineating a region of craniofacial dysmorphology may circumscribe brain regions where development has gone awry. Embryologic fate-maps predict that the frontonasal-maxillary junctural region implicated in schizophrenia corresponds to the interface of the diencephalon and mesencephalon. Based on our craniofacial findings, we predicted that brain maldevelopment in schizophrenia might arise at this interface. Our preliminary studies of schizophrenia have borne out this prediction, revealing a marked deviation of the anterior-posterior brain midline above the diencephalic-mesencephalic border. Notably, the brain midline deviation and frontonasal-maxillary junctural dysmorphology are significantly correlated within subjects, further corroborating this model. We have also observed marked brain midline deviations among siblings of these probands which if confirmed, raises the possibility that these forms of dysmorphology are tapping a pathogenic process that is transmissible. In this project, we propose to: (1) determine the extent to which the brain midline, imaged by magnetic resonance, is deviant in schizophrenia and (2) establish the specificity of these findings to schizophrenia, employing a contrast group with bipolar affective disorder. (3) Further, we will ascertain whether midline deviation is over-represented among non-psychotic siblings of schizophrenic probands, and determine if these deviation scores are positively correlated with thought disorder and other clinical variables among probands and their siblings. (4) Finally, we will document the degree to which brain and face dysmorphology coheres within subjects, as predicted by the embryological model.

描述：（逐字研究申请人的摘要）： 项目是大脑玛尔达开发的胚胎学模型，该模型源自我们 精神分裂症的颅面畸形研究。在两个初步研究中 以及最近的复制，我们发现过多 精神分裂症患者及其亲戚的脑畸形。如何 这些发现可能与脑畸形发生有关吗？因为大脑和 面部由共享胚胎起源，遗传偏差或环境产生 胚胎发生过程中的侮辱可以在大脑中表现出来 颅面形成。因此，描绘了颅面的区域 畸形学可能会限制发育趋势的大脑区域。 胚胎命运映射预测，额叶 - 大小交叉区域 与精神分裂症有关 和中脑。根据我们的颅面发现，我们预测了大脑 精神分裂症中的MALDEVEMENT可能会在此界面出现。 我们对精神分裂症的初步研究已经实现了这一预测， 揭示了前后大脑中线的明显偏差 双脑 - 脑脑边界。值得注意的是，大脑中线偏差和 额骨 - 大小交关连接症畸形显着相关 在受试者中，进一步证实了这一模型。我们还观察到了标记 这些证据的兄弟姐妹之间的大脑中线偏差，如果确认， 提高了这些形式的畸形形式正在窃听A 可传播的致病过程。在这个项目中，我们建议：（1） 确定磁共振成像的大脑中线的程度， 在精神分裂症和（2）建立这些发现的特异性 对精神分裂症，采用造影群患有双相情感障碍。 （3）此外，我们将确定中线偏差是否过多 在精神分裂症的非精神病性兄弟姐妹中，并确定这些是否是否 偏差分数与思想障碍和其他 概率及其兄弟姐妹之间的临床变量。 （4）最后，我们将 记录大脑和面对畸形学相干的程度 如胚胎学模型所预测的那样。