BRAIN MIDLINE MALFORMATION IN SCHIZOPHRENIA

描述：（逐字摘自申请人摘要）：这样做的动力 该项目是脑发育不良的胚胎学模型，源自我们的 精神分裂症的颅面畸形研究。在两项初步研究中 和最近的复制，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。如何 这些发现可能与大脑畸形发生有关吗？因为大脑和 面孔源于共同的胚胎起源、遗传偏差或环境 胚胎发生过程中的损伤可以在大脑和 颅面结构。因此，划定颅面区域 畸形可能限制了发育出错的大脑区域。 胚胎命运图预测额鼻-上颌结合区 与精神分裂症有关的对应于间脑的界面 和中脑。根据我们的颅面发现，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上。 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线上方的明显偏差 间脑-中脑边界。值得注意的是，大脑中线偏差和 额鼻-上颌结合部形态异常显着相关 在受试者内部，进一步证实了这一模型。我们还观察到标记 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， 提出了这些形式的畸形正在利用一种可能性 具有传染性的致病过程。在这个项目中，我们建议：（1） 通过磁共振成像确定大脑中线的程度， 在精神分裂症中存在异常，并且 (2) 确定这些发现的特异性 对于精神分裂症，采用患有双相情感障碍的对照组。 (3)进一步，我们将确定中线偏差是否被过度代表 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等呈正相关 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一致性程度 正如胚胎学模型所预测的那样。

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.