DEFINING CASENESS FOR PSYCHIATRIC LINKAGE STUDIES

这是对NIMH科学家发展奖(K-21)的请求，题为 《定义精神病学关联研究中的偶然性》这个 应聘者的主要兴趣是猪瘟的遗传流行病学 神经精神障碍。精神病学的一个根本问题 遗传学是对表型的定义。候选人的培训为 一位专注于双相情感障碍的精神病学家和流行病学家吸引了她 对这一问题的关注，以及她最近在遗传学方面的工作 阿尔茨海默氏症为它提供了一个新的视角。很明显，她 现有的技能将她限制在精神病学上，主要是直截了当的方法。 诊断，以及遗传学的概念性方法。因此，支持 因为需要额外的培训，让她能够更深入地研究 阿尔茨海默病和其他痴呆症的诊断， 并学习心理测量学和其他技术来描绘和 描述病理学。还需要支持，以使她能够 对遗传学的更技术性的理解，包括建模， 模拟和连锁性分析。 旨在补充这一培训的研究项目涉及 制定用于分类的确定性或干酪性的量度 精神病学连锁研究中模棱两可的表型。该项目包括 构建平坦度指数，交叉验证该指数，并测试其 提高连锁分析能力。它涉及到两个方面的工作 不同的分类问题：阿尔茨海默病的鉴别 远离其他痴呆症，并描绘出哪些单极亲属 就双极链接研究而言，应将其视为两极。 除了它的教育学价值之外，同时研究两种障碍可能 有助于推广适用于其他疾病的方法。这一集成 培训和研究的结合将有助于培养候选人的 发展成为对该综合体感兴趣的临床研究人员 精神病学与遗传学研究的关系 精神错乱。

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.