BRAIN MIDLINE MALFORMATION IN SCHIZOPHRENIA

精神分裂症的脑中线畸形

• 批准号: 6539032
• 负责人: CURTIS KIMBALL DEUTSCH
• 金额: $ 18.75万
• 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 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6539032
• 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：(逐字摘自申请者摘要)：这一点的动力 项目是大脑发育不良的胚胎学模型，源于我们的 精神分裂症的颅面畸形研究。在两项初步研究中 在最近的一次复制中，我们发现额鼻-上颌骨过多 精神分裂症患者及其亲属的交界畸形。多么 这些发现是否与脑畸形发生有关？因为大脑和 面孔源于共同的胚胎起源、基因偏差或环境 胚胎发育期间的侮辱可以在大脑和大脑中表现出来 头面部结构。因此，勾画出一个颅面区域 畸形可能局限于发育出现问题的大脑区域。 胚胎学命运图预测额鼻-上颌交界区 与精神分裂症有关对应于间脑的界面 和中脑。根据我们的头面部发现，我们预测大脑 精神分裂症的发育不良可能在这个界面上出现。 我们对精神分裂症的初步研究证实了这一预测， 显示大脑前后部中线明显偏离 间脑-中脑交界处。值得注意的是，大脑中线偏差和 额鼻-上颌交界畸形显著相关 在受试者内部，进一步证实了这一模型。我们还观察到了明显的 这些先证者的兄弟姐妹之间的大脑中线偏差如果得到证实， 增加了这些形式的畸形正在利用一种 可传播的致病过程。在这个项目中，我们建议：(1) 确定通过磁共振成像的大脑中线的程度， 精神分裂症患者是否异常，以及(2)确定这些发现的特异性 对于精神分裂症，采用双相情感障碍的对照组。 (3)此外，我们会确定中线偏差是否过高 精神分裂症先证者的非精神病兄弟姐妹，并确定这些 偏差分数与思维障碍和其他 先证者及其兄弟姐妹的临床变量。(4)最后，我们将 记录大脑和面部畸形在多大程度上一致 受试者，正如胚胎学模型所预测的那样。