Measurement and Multimethod Validation of Alcohol Use Disorder Etiologic Mechanisms

项目总结 酒精使用障碍(AUD)是一个重大的公共健康问题，但治疗效果并不明显 疗效，可能是由于AUD的深刻表型异质性。为了提高AUD的疗效 对于治疗，必须更好地描述这种异质性，这反过来可能更清楚地阐明 精准医学途径的治疗目标。这可能需要改变澳元的概念化 从临床描述和病因机制，一种方法体现了一些现代的目标 成瘾研究领域标准(AARDoC)和成瘾等对成瘾的认识 神经临床评估(ANA)。然而，目前的研究表明，AARDoC和ANA患有 重要的缺点，包括临床效率有限，因此可能受益于进一步的发展， 精炼和验证。为了解决这些缺点，拟议的项目旨在：(A)从经验上测试 包括ANA在内的现代概念性和病因学框架所阐述的模型，以及(B)得出 基于机制的计算机自适应测验(CAT)评估AUD 测试建设和以社区为基础的参与式研究战略。首先，候选人的一套自我报告 由病因学、基于理论、个体发生学层次(ETOH)阐述的13个病因学领域的条目索引 作为AARDoC/ANA最近延伸的AUD机制框架将源自 将使用文献和两轮认知访谈来完善不同群体中的项目集 参与者(N=50)，有危险或有害的酒精使用。接下来，项目将被管理到一个合并的 社区和临床样本(N=1,200)对条目结构进行经验性检验并确定最佳匹配 模特。然后将使用项目反应理论来校准项目，以便为每个项目建立CAT 确定的领域(例如，奖励、认知控制、消极情绪性)。使用经过改进和校准的 项目集和特定领域的猫，数据将从额外的独立样本Heavy收集 饮酒者(N=100)。超过14天的生态瞬时评估和后续评估也将 进行的目的是评估猫在生态有效的环境中的心理测量特性，以及 随着时间的推移。具体地说，为了确定特定于域的CAT是否证明有效性(例如，收敛， 区分、预测)和可靠性(例如，重测)跨越不同的患者群体和性别/性别 组。所有研究目标将与有生活经验的个人一起进行，并与之协商。 以确保该措施是可接受的、可行的，并充分考虑到具体情况。这个项目是一致的 与NIAAA的战略计划，特别是目标1(确定酒精相关病理机制)和目标2 (改进AUD的诊断和跟踪)。由此产生的措施也有可能支持进展 通过促进对以下机制的评估，实现目标4(开发和改进AUD的治疗 可作为AUD治疗的可行靶点，包括行为和药物干预。

PROJECT SUMMARY Alcohol use disorder (AUD) is a significant public health problem, yet treatments demonstrate only modest efficacy, likely due to the the profound phenotypic heterogeneity of AUD. In order to improve the efficacy of AUD treatments, it is imperative to better characterize this heterogeneity which may, in turn, elucidate clearer treatment targets for precision medicine approaches. This likely requires shifting conceptualizations of AUD away from clinical description and towards etiologic mechanisms, an approach embodied by the goals of some modern conceputalizations of AUD, such as the Addiction Research Domain Criteria (AARDoC) and Addictions Neuroclinical Assessment (ANA). However, current research suggests that AARDoC and ANA suffer from important shortcomings, including limited clinical efficiency, and may therefore benefit from further development, refinement, and validation. To address these shortcomings, the proposed project aims to (a) empirically test the models articulated by modern conceptual AUD etiological frameworks, including the ANA, and (b) derive a mechanism-based computerized adaptive test (CAT) assessment of AUD developed using principles of objective test construction and community-based participatory research strategies. First, a candidate set of self-report items indexing 13 etiologic domains articulated by the Etiologic, Theory-Based, Ontogenetic Hierarchical (ETOH) framework of AUD mechanisms, which serves as a recent extension of AARDoC/ANA, will be derived from the literature and two rounds of cognitive interviews will be used to refine the item set among a diverse group of participants (N = 50) with hazardous or harmful alcohol use. Next, items will be administered to a combined community and clinical sample (N = 1,200) to empirically test the structure of items and determine the best-fitting model. Item response theory will then be used to calibrate the items for the purpose of building a CAT for each of the domains identified (e.g., reward, cognitive control, negative emotionality). Using the refined and calibrated item set and domain-specific CATs, data will be collected from an additional independent sample of heavy drinkers (N = 100). Ecological momentary assessment over 14 days and a follow-up assessment will also be conducted with the goal of evaluating the psychometric properties of the CATs in ecologically valid contexts and over time. Specifically, to determine if the domain-specific CATs demonstrate validity (e.g., convergent, discriminant, predictive) and reliability (e.g., test-retest) across diverse patient populations and sex/gender groups. All research aims will be conducted alongside and in consultation with individuals with lived experience of AUD to ensure the measure is acceptable, feasible, and adequately contextualized. This project is consistent with NIAAA's Strategic Plan, specifically Goal 1 (Identify mechanisms of alcohol-related pathology) and Goal 2 (Improve diagnosis and tracking of AUD). The resulting measure also has the potential to support progress towards Goal 4 (Develop and improve treatments for AUD) by facilitating the assessment of mechanisms that may serve as viable targets in AUD treatments, including behavioral and pharmacological interventions.