DEFINING CASENESS FOR PSYCHIATRIC LINKAGE STUDIES

这是一个NIMH科学家发展奖（K-21）的要求， “为精神病学关联研究定义病例。“那 候选人的主要兴趣是遗传流行病学， 神经精神障碍 精神病学的一个基本问题 遗传学是表现型的定义。 候选人的培训作为 一位专注于双相情感障碍的精神病学家和流行病学家 注意这个问题，以及她最近在遗传学方面的工作， 老年痴呆症让我们有了新的认识。 很明显，她 现有的技能限制了她的精神病，主要是分类的方法 诊断，以及对遗传学的概念性研究。 因此，支持 要求她接受额外的培训， 阿尔茨海默病和其他痴呆症的诊断， 并研究心理测量和其他技术， 描述病理学。 还要求提供支持，使她能够发展 对遗传学的更技术性的理解，包括建模， 模拟和链接分析。 旨在补充这一培训的研究项目涉及 发展确定性或案例性的衡量标准， 精神病学联系研究中的模糊表型。 该项目包括 构建案件指数，交叉验证指数，并测试其 提高联动分析能力。 它涉及到两个方面的工作 老年痴呆症的症状有哪些？ 从其他痴呆疾病中分离出来，并描述哪些单极亲属 为了双极联系研究的目的，应将其视为双极。 除了其教学价值，同时研究两种疾病可能 有助于推广到其他疾病的方法。 这一综合 培训和研究的结合将有助于培养候选人的 作为一名对复杂的 精神疾病分类学与遗传学调查的关系 紊乱

This is a request for an NIMH Scientist Development Award (K-21) entitled "Defining Caseness for Psychiatric Linkage Studies." The Candidate's primary interest is in the genetic epidemiology of neuropsychiatric disorders. A fundamental problem for psychiatric genetics is the definition of the phenotype. The candidate's training as a psychiatrist and epidemiologist focussed on bipolar disorder drew her attention to this issue, and her recent work on the genetics of Alzheimer's disease put it in a new light. It became clear that her existing skills limited her to a psychiatric, mainly categorical approach to diagnosis, and a mostly conceptual approach to genetics. Thus, support for additional training is requested to allow her to delve much deeper into the diagnosis of Alzheimer's disease and other dementing disorders, and to study psychometric and other techniques for delineating and describing pathology. Support is also requested to allow her to develop a more technical understanding of genetics including modelling, simulations, and linkage analysis. The research project designed to complement this training involves the development of a measure of certainty or caseness for classification of ambiguous phenotypes in psychiatric linkage studies. The project includes constructing a caseness index, cross-validating the index, and testing its ability to improve the power of linkage analysis. It involves work on two different classification problems: differentiating Alzheimer's disease from other dementing illnesses, and delineating which unipolar relatives ought to be considered bipolar for purposes of bipolar linkage studies. In addition to its pedagogic value, work on two disorders side by side may contribute to methods generalizable to other disorders. This integrated combination of training and research will serve to foster the Candidate's development as a clinical investigator interested in the complex relationship of nosology and genetic investigation of psychiatric disorders.