Epidemiology of Prenatal Exposures in Schizophrenia

描述（由申请人提供）：在这个拟议的职业发展奖中，我的目标是建立在我之前的职业奖的基础上。在该奖项的资助下，我在三个出生队列中检查了产前侮辱与成人精神分裂症谱系障碍（SSD）之间的关系，并确定了几个新的关联。在目前的奖项中，我将从几个方面扩展这项工作。首先，我将调查早期发育暴露是否与SSD风险增加有关。其次，我将评估早期发育暴露是否与SSD患者的大脑结构和功能异常有关。第三，我将研究遗传易感性与SSD早期发育损伤的关系。为了实现这一目标，我将接受神经影像学、遗传流行病学和其他研究领域知名专家的进一步培训。这将包括直接指导、正式课程、阅读和研讨会。该奖项的研究部门将利用我在两个出生队列中完成的精神分裂症随访研究中获得的产前病毒感染和其他早期发育损伤的前瞻性数据。与以往的研究不同，血清学分析将用于记录产前病毒暴露和细胞因子升高与精神分裂症风险的关系。这些队列中的受试者将接受神经影像学评估，包括体积磁共振成像（MRI）和质子磁共振波谱（1H MRS），以及全面的神经心理测试。然后将根据上述方法检测到的特定结构和功能脑异常来检查早期发育损伤的总结措施。在提案的遗传学部分，我将测试基因-环境相互作用的模型。

DESCRIPTION (provided by applicant): In this proposed career development award, I aim to build upon the work of my previous career award. Funded by that award, I examined the relation between prenatal insults and adult schizophrenia spectrum disorders (SSD) in three birth cohorts, and identified several novel associations. In the current award I will extend this work in several ways. First, I will investigate whether early developmental exposures are associated with an increased risk of SSD. Second, I will assess whether early developmental exposures are associated with structural and functional brain abnormalities in patients with SSD. Third, I will examine the relation of genetic vulnerability to early developmental insult in SSD. To achieve this objective I will receive further training in neuroimaging, genetic epidemiology, and other research areas from distinguished experts. This will include direct supervision, formal coursework, readings, and seminars. The research arm of the award will utilize prospectively acquired data on prenatal viral infection and other early developmental insults in two birth cohorts in which I have completed follow-up studies for schizophrenia. Unlike previous studies, serologic analysis will be used to document prenatal viral exposures and cytokine elevations in relation to the risk of schizophrenia. Subjects in these cohorts will receive neuroimaging assessments, including volumetric magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H MRS), and a comprehensive neuropsychological test battery. A summary measure of early developmental insult will then be examined in relation to specific structural and functional brain abnormalities detected by the above methodologies. In the genetics section of the proposal, I will test models of gene-environment interaction.