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)框架是一种启发式方法，将神经科学与精神病理学相结合。因此，RDoC是试图开发这样的结构：(A)连接分析单元，(B)适用于已建立的诊断标准，以及(C)是提供有助于深入了解精神疾病的可测量结构的起点。然而，缺乏来自实验测量的可靠、强大的潜在结构是沿着可以映射到多个分析单元的维度组织精神障碍的关键障碍。我们使用自我报告、行为、生理学和神经回路单元的分析方法，专注于RDoC提出的正负价系统域，并将它们应用于从初级保健招募的患有焦虑或抑郁的临床人群。 诊所跨越两个地点，并应用潜变量分析，得出跨越分析单元的正价系统和负价系统功能的潜在结构。该提案的具体目标是：(1)招募、评估和分析自我报告、行为、生理和神经回路分析数据单元，从n=100名寻求治疗的队列中的探索性样本中招募、评估和分析在加州大学圣迭戈分校和加州大学洛杉矶分校初级保健诊所就诊的个人。(2)使用相同的测量方法在两个地点获得n=100名受试者的验证性样本，以确定从探索性样本获得的潜在结构的重复性和稳健性。(3)在加州大学圣迭戈分校和加州大学洛杉矶分校获得n=50人的可靠性样本，并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广义的焦虑或抑郁患者样本中调查正价和负价的神经指数。现有对情绪障碍神经过程的研究仅限于相对较小的样本量。通过整合两个站点的资源，我们将招募足够大的样本来进行比以往任何时候都更全面的分析。一旦建议的目标完成，我们将有一个健壮和可靠的维度变量集，基于潜变量方法量化正负价域。这些变量捕获了临床差异，并将从两个不同的临床位置获得，以提供负价域和正价域的共性的经验证据。这些变量随后将被用来确定：(A)它们是否可以被用来预测一个人对药物或行为治疗的反应如何；(B)它们是否可以对专门旨在改变正或负价系统的治疗做出不同的反应；以及(C)它们是否可以用于随后的焦虑和抑郁的计算和/或神经过程模型，以更基本地了解这些人的病理。

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.