Neuroimaging, pharmacological and genetic studies of the oculomotor system in healthy and schizophrenic individuals

眼动控制缺陷是精神分裂症的内表型。在一个由DFG Emmy Noether项目资助的项目中，我正在研究遗传多态性与平滑追求和反扫视眼运动的关系以及它们潜在的神经机制。这项工作将有助于我们理解精神分裂症风险多态性的机制途径。在最初的申请（2007年3月提交）中，我提议研究120名诊断为精神分裂症的患者和120名健康对照者。然而，最近来自我们小组和其他人的证据表明，需要更大的发现样本和独立的复制样本相结合，才能可靠地显示神经认知和动眼力水平的基因效应。因此，我想申请获得资金，用于(1)招募和测试另外400名健康志愿者来执行动眼肌（以及神经心理学）任务；(2)提取DNA并对精神分裂症风险多态性进行基因分型。将这一发现样本与一部分参与者的神经成像数据以及从国际合作中获得的大量复制样本相结合，将使我能够建立一个关于动眼肌内表型和分子遗传学的实质性数据库。该数据库将首次允许可靠地评估风险多态性与这些已证实的精神分裂症内表型之间的关联。

Deficits in oculomotor control are well validated endophenotypes of schizophrenia. In a project currently funded by a DFG Emmy Noether Programme I am investigating associations of genetic polymorphisms with smooth pursuit and antisaccade eye movements as well as their underlying neural mechanisms. This work will contribute towards our understanding of the mechanistic pathways of schizophrenia risk polymorphisms. In the original application (submitted March 2007) I proposed to study 120 patients with a diagnosis of schizophrenia and 120 healthy controls. However, recent evidence from our group as well as others has shown that much larger discovery samples in combination with independent replication samples are needed to reliably show gene effects at the neurocognitive and oculomotor level. Therefore, I would like to apply to obtain funding for (1) recruiting and testing a further 400 healthy volunteers to perform oculomotor (as well as neuropsychological) tasks and (2) extracting DNA and genotyping schizophrenia risk polymorphisms. The proposed extension of this discovery sample in combination with neuroimaging data on a subset of participants as well as large replication samples drawn from international collaborations would allow me to build up a substantial database of oculomotor endophenotypes and molecular genetics. This database would allow, for the first time, reliably assessing associations between risk polymorphisms and these well validated schizophrenia endophenotypes.