Statistical Methods for Developing RDoC-based Multidimensional Profiles

描述（由申请人提供）：Meredith Lotz Wallace博士的长期研究目标是成为一名精神病学生物统计学家，他开发并应用新方法来帮助研究人员实现NIMH研究领域标准（RDoC）项目的目标。RDoC项目表明，精神障碍的理想特征可能是体征和症状的多个维度（例如，脑回路、生理、行为和自我报告）；然而，这种新范式带来了巨大的挑战，因为大多数现有的统计方法都没有设计成能够容纳数据类型的混合。华莱士博士提出的指导研究科学家发展（K01）奖是她实现长期研究目标的第一步；它将为她提供开发统计方法所需的培训和支持，使RDoC项目成为一个更可行的研究框架。Wallace博士的K01的总体目标是开发和应用新的聚类方法，将多种类型的密集测量数据结合起来。在目标1中，Wallace博士将开发聚类方法，将通过多导睡眠图、活动图和日常自我报告测量获得的密集测量数据结合起来。这些方法将在两种不同的理论框架下开发，以增强它们在K01中专门讨论的应用之外的泛化性。在目标2中，Wallace博士将把她的方法应用到一个数据库中，该数据库包含1000多名个体的多维观察结果，这些个体具有与丧失、焦虑和睡眠/觉醒调节相关的各种程度的干扰。这些方法的应用将揭示多维的概况，可能跨越目前基于dsm的诊断。对这些概况的研究将澄清迹象和症状的多个维度在多大程度上是一个真正的连续体，还是分成离散的类别。虽然候选人的生物统计学背景为她开始这项研究做好了准备，但其成功完成最终取决于三个领域的额外培训：1)聚类和密集测量数据方法的数学基础，2)负效价系统（例如，损失和焦虑），以及3)睡眠/觉醒调节。这种培训将通过辅导课、指导阅读、正式课程、实际临床工作和专业会议来实现。为了实现她的培训目标，华莱士博士组建了一支由临床和方法论导师和顾问组成的强大团队。临床指导团队由Ellen Frank博士领导，她是国际公认的情绪相关疾病专家。方法指导团队由Satish Iyengar博士领导，他是精神病学统计领域的领导者，在集中和建模密集测量数据方面具有专业知识。这个项目的培训和研究将为Wallace博士提供她在K01的第四年提交R01所需的经验和技能。该R01将允许Wallace博士扩展她提出的方法，并将其应用于基于额外维度和研究领域的基于rdoc的多维概况。

DESCRIPTION (provided by applicant): Dr. Meredith Lotz Wallace's long-term research goal is to become a psychiatric biostatistician who develops and applies novel methods to aid researchers in attaining the goals of the NIMH Research Domain Criteria (RDoC) project. The RDoC project suggests that mental disorders may be ideally characterized by multiple dimensions of signs and symptoms (e.g., brain circuitry, physiology, behavior, and self-report); however, this new paradigm poses substantial challenges because most existing statistical methods were not designed to accommodate the resulting mixture of data types. Dr. Wallace's proposed Mentored Research Scientist Development (K01) award is the first step towards her long-term research goal; it will provide the training and support she needs to develop statistical methods that will make the RDoC project a more viable research framework. The overall aim of Dr. Wallace's K01 is to develop and apply novel clustering methods that incorporate multiple types of intensively measured data. In Aim 1, Dr. Wallace will develop clustering methods that incorporate intensively measured data captured through polysomnography, actigraphy, and daily self-report measures. These methods will be developed under two different theoretical frameworks to enhance their generalizability to applications beyond those addressed specifically in the K01. In Aim 2, Dr. Wallace will apply her methods to a data base containing multiple dimensions of observations from over 1000 individuals with a variety of levels of disturbances related to loss, anxiety, and sleep/wake regulation. The methods' application will reveal multidimensional profiles that may cut across the current DSM-based diagnoses. A study of these profiles will clarify the extent to which the multiple dimensions of signs and symptoms lie on a true continuum or separate into discrete classes. Although the candidate's background in biostatistics has primed her to begin this research, its successful completion ultimately hinges on additional training in three areas: 1) mathematical foundations of methods for clustering and intensively measured data, 2) negative valence systems (e.g., loss and anxiety), and 3) sleep/wake regulation. This training will be achieved through tutorials, directed readings, formal coursework, hands-on clinical work, and professional conferences. To achieve her training goals, Dr. Wallace has assembled a strong team of clinical and methodological mentors and consultants. The clinical mentoring team is led by Dr. Ellen Frank, an internationally recognized expert in mood-related disorders. The methodological mentoring team is led by Dr. Satish Iyengar, a leader the field of psychiatric statistics with expertise in clustering and modeling intensively measured data. The training and research resulting from this project will provide Dr. Wallace with the experience and skills she needs to submit an R01 in the fourth year of the K01. This R01 will allow Dr. Wallace to expand on her proposed methods and apply them to develop RDoC-based multidimensional profiles based on additional dimensions and domains of study.