Latent Constructs: Negative-Positive Valence Domains in Anxiety and Depression

描述（由申请人提供）：NIMH研究领域标准（RDoC）框架是一种将神经科学与精神病理学相结合的启发式方法。因此，RDoC是试图开发的结构，（a）连接跨单元的分析，（B）是适用于整个既定的诊断标准，（c）是一个出发点，以提供可测量的结构，将有助于获得更深入的了解精神疾病。然而，缺乏可靠的，强大的潜在结构来自实验的措施是一个关键的障碍，组织精神障碍沿着维度，可以映射到多个单元的分析。本研究以RDoC所提出的正、负效价系统领域为研究对象，采用自我报告、行为、生理和神经回路单元的分析方法，将其应用于从基层医疗机构招募的焦虑或抑郁个体的临床人群 诊所在两个网站，并应用潜在变量分析，以获得潜在的建设积极和消极的效价系统功能，切断跨单位的分析。该提案的具体目的是：（1）招募、评估和分析来自UCSD和UCLA初级保健诊所的n=100名寻求治疗的个体队列的探索性样本中的自我报告、行为、生理和神经回路分析数据。(2)使用相同的测量方法在两个研究中心获得n=100例受试者的确证性样本，以确定从探索性样本中获得的潜在结构的重现性和耐用性。(3)在UCSD和UCLA获得n=50人的可靠性样本，将在一个月内重新测试，以确定潜在结构的可靠性。这将是第一次在同一个广泛定义的焦虑或抑郁患者样本中研究正效价和负效价的神经指标。现有的情绪障碍神经过程的研究仅限于相对较小的样本量。通过整合两个研究中心的资源，我们将招募足够大的样本，进行比以往任何时候都更全面的分析。一旦完成了所提出的目标，我们将有一个强大的和可靠的维度变量集，量化的基础上的潜变量方法的积极和消极的效价域。这些变量捕获临床方差，并将从两个不同的临床研究中心获得，以提供负和正效价域的一般性的经验证据。这些变量随后将用于确定（a）它们是否可以用作个体对药理学或行为治疗的反应如何的预测因子;（B）它们可以对特别旨在修饰正或负价系统的疗法有差异反应，以及（c）它们可以用于焦虑和抑郁的后续计算和/或神经过程模型，以获得对这些个体中发生的病理学的更基本的理解。

DESCRIPTION (provided by applicant): The NIMH Research Domain Criteria (RDoC) framework is a heuristic approach to integrate neuroscience with psychopathology. Thus, RDoC is the attempt to develop constructs that (a) connect across units of analysis, (b) are applicable across established diagnostic criteria, and (c) are a point of departure to provide measurable constructs that will be useful to gain a deeper understanding of psychiatric conditions. However, the lack of reliable, robust latent constructs derived from experimental measures is a critical barrier to organizing mental disorders along dimensions that can be mapped onto multiple units of analysis. We focus on the positive and negative valence system domains proposed by the RDoC using self-report, behavior, physiology, and neural circuit unit of analysis measures, apply them to a clinical population of individuals with anxiety or depression recruited from primary care clinics across two sites, and apply latent variable analysis to derive latent constructs of positiv and negative valence systems functioning that cut across units of analyses. The specific aims of the proposal are: (1) To recruit, assess, and analyze self-report, behavioral, physiological, and neural circuit unit of analysis data in an exploratory sample from a cohort of n=100 treatment seeking individuals presenting to primary care clinics at UCSD and UCLA. (2) To obtain a confirmatory sample of n=100 subjects at both sites using the same measurement approaches to determine the reproducibility and robustness of the latent constructs obtained from the exploratory sample. (3) To obtain a reliability sample of n=50 individuals at UCSD and UCLA that will be re-tested within a month to determine the reliability of the latent constructs. This wll be the first time neural indices of positive valence and negative valence are investigated within the same broadly defined sample of anxious or depressed patients. Extant studies of neural processes in emotional disorders are limited to relatively small sample sizes. By combining resources across two sites, we will recruit a large enough sample to conduct more comprehensive analyses than ever before achieved. Once the proposed aims are completed, we will have a robust and reliable dimensional set of variables that quantify the positive and negative valence domains based on a latent variable approach. These variables capture clinical variance and will have been obtained from two different clinical sites to provide empirical evidence of the generality of the negative and positive valence domains. These variables will subsequently be used to determine whether (a) they can be used as predictors for how well an individual will respond to pharmacological or behavioral treatment; (b) they can be differentially responsive to therapies that are specifically aimed at modifying the positive or negative valence systems, and (c) they can be used in subsequent computational and/or neural process models of anxiety and depression to gain a more fundamental understanding of the pathology that occurs in these individuals.