BRAIN MIDLINE MALFORMATION IN SCHIZOPHRENIA

精神分裂症的脑中线畸形

• 批准号: 6392692
• 负责人: CURTIS KIMBALL DEUTSCH
• 金额: $ 18.71万
• 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/6392692
• 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：（来自申请人摘要的逐字逐句）： 这个项目是一个大脑发育不良的胚胎学模型， 精神分裂症的颅面畸形学研究在最初的研究中， 和最近的一次复制我们发现额鼻上颌骨 精神分裂症患者及其亲属交界处畸形如何 这些发现是否与脑畸形有关？因为大脑和 面部起源于共同的胚胎起源，遗传变异或环境 胚胎发育过程中的损伤可以在大脑中表现出来， 颅面结构因此，描绘颅面的区域 畸形可能会限制大脑区域的发展已经出了差错。 胚胎命运图预测额鼻上颌交界区 与精神分裂症有关的神经节对应于间脑的界面 和中脑基于我们的颅面发现，我们预测大脑 精神分裂症的发育不良可能出现在这个界面。 我们对精神分裂症的初步研究证实了这一预测， 揭示了大脑前后中线在大脑中动脉上方的明显偏离。 间脑-中脑缘值得注意的是，大脑中线偏离和 额鼻-上颌交界处的畸形与 进一步证实了这一模型。我们还观察到， 这些先证者的兄弟姐妹之间的大脑中线偏离，如果得到证实， 提出了这些畸形形式正在利用 可传播的致病过程。在本项目中，我们建议：（1） 通过磁共振成像， 在精神分裂症中是异常的，（2）建立这些发现的特异性 以双相情感障碍为对照组。 (3)此外，我们将确定中线偏离是否过多 在精神分裂症先证者的非精神病兄弟姐妹中，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之间的临床变量。(4)最后我们将 记录大脑和面部畸形的程度， 正如胚胎学模型所预测的那样。