Twin Modeling of Individual Symptoms of Depression and Generalized Anxiety: A Symptom Network Approach

项目总结/摘要 该奖学金的目标是进一步发展申请人的知识和技能， 计算方法（即，双胞胎模型和网络模型），重度抑郁症的共病性 焦虑症（MDD）和广泛性焦虑症（GAD），以及基础神经科学和遗传学。符合 这些目标，申请人的培训的基石将是他接受的统计和理论培训 通过研讨会，课程，每年访问弗吉尼亚联邦大学（VCU），以满足博士。 吉莱斯皮和尼尔，定期赞助商和共同赞助商会议，和专业发展活动。的 项目将作为申请人的论文，并帮助他追求成为一个独立的目标 使用大型数据集和多方法实验室研究的高级计算分析的研究者 研究抑郁和焦虑表型的病因、维持和复发。除了有 申请人获得的技能，项目的目标将大大促进对MDD的理解， 通过测试新型精神病理学理论（网络理论）的中心原则来研究GAD症状病因。 了解症状的原因及其协方差是至关重要的，因为不同的因果模型 对干预的不同影响。此外，该研究与NIMH的战略一致， 目的是定义复杂行为的机制以及NIH对可复制性的日益重视。 一些双胞胎研究已经估计了个体MDD的遗传和环境病因 症状然而，没有研究认为症状之间的因果关系的可能性， 网络理论的假设。因此，本研究将使用一种新的方法-方向 因果关系（DoC）建模-双胞胎数据，以（1）测试个体MDD和 GAD症状，并估计遗传和环境对每种症状的贡献，（2）评估GAD症状的遗传和环境因素。 目的1中最佳拟合模型在独立双胞胎样本中的可重复性，以及（3）探索 每个症状的表型因果途径和遗传与环境责任。该项目大大 扩展了先前对个别MDD症状的研究，方法是测试 网络理论，并包括MDD和GAD症状在同一模型中，这是重要的，因为他们 这两种疾病的症状之间存在高度共病性和潜在的因果关系。导师对此 该项目将由孪生和DoC建模，网络理论和建模， 抑郁症和焦虑症的合并症，神经科学（发起人：Shankman，吉莱斯皮和弗里德; OSCs：Neale，Roitman）。该奖学金不仅是申请人研究生涯中的重要一步， 但这项研究的主要目的是测试症状共现的不同因果模型， 量化每种症状的遗传和环境贡献将对以下方面产生重要影响： MDD和GAD症状的预防和治疗以及症状病因学理论。

Project Summary/Abstract The goals of this fellowship are to further develop the applicant's knowledge and skills in advanced computational methods (i.e., twin modeling and network modeling), the comorbidity of Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD), and basic neuroscience and genetics. In line with these goals, a cornerstone of the applicant's training will be the statistical and theoretical training he receives through workshops, coursework, annual visits to Virginia Commonwealth University (VCU) to meet with Drs. Gillespie and Neale, regular sponsor and co-sponsor meetings, and professional development activities. The project will serve as the applicant's dissertation and help him pursue his goal of becoming an independent investigator who uses advanced computational analyses of large datasets and multi-method laboratory studies to study the etiology, maintenance, and recurrence of phenotypes of depression and anxiety. In addition to the skills to be gained by the applicant, the project's goals will greatly advance the understanding of MDD and GAD symptom etiology by testing the central tenet of a novel theory of psychopathology (network theory). Understanding the causes of symptoms and their covariance is critical, as different causal models have markedly different implications for intervention. Additionally, the study is consistent with the NIMH's strategic objective to define mechanisms of complex behaviors and NIH's increased emphasis on replicability. Several twin studies have estimated the genetic and environmental etiology of individual MDD symptoms. However, no studies have considered the possibility of causal relationships between symptoms as hypothesized by the network theory. The present study will therefore use a novel method - direction of causation (DoC) modeling - of twin data to (1) test putative causal relationships between individual MDD and GAD symptoms and estimate the contributions of genetics and environment to each symptom, (2) evaluate the replicability of the best fitting model in aim 1 in an independent twin sample, and (3) explore sex differences in the phenotypic causal pathways and genetic and environmental liabilities of each symptom. This project greatly extends prior studies of individual MDD symptoms by testing putatively causal pathways hypothesized by the network theory and including both MDD and GAD symptoms in the same model, which is important given their high comorbidity and potential causal relationships between symptoms of the two disorders. Mentorship for this project will be provided by experts in the areas of twin and DoC modeling, network theory and modeling, the comorbidity of depressive and anxiety disorders, and neuroscience (sponsors: Shankman, Gillespie, and Fried; OSCs: Neale, Roitman). This fellowship will not only be an important step in the applicant's research career, but the proposed study's primary objective of testing different causal models of symptom co-occurrence and quantifying the genetic and environmental contributions to each symptom will have important implications for the prevention and treatment of MDD and GAD symptoms and for theories of symptom etiology.