Measurement and Multimethod Validation of Alcohol Use Disorder Etiologic Mechanisms

项目摘要 酒精使用障碍（AUD）是一个重要的公共卫生问题，但治疗方法仅显示出适度的 疗效，可能是由于AUD的表型异质性。为了提高AUD的疗效， 治疗，必须更好地表征这种异质性，这反过来可以更清楚地阐明 精准医疗方法的治疗目标。这可能需要改变澳元的概念 从临床描述和病因机制，一个方法体现了一些现代的目标， AUD的概念化，如成瘾研究领域标准（AARDoC）和成瘾 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，包括有限的临床效率，因此可能受益于进一步的发展， 精炼和验证。为了解决这些不足之处，拟议的项目旨在（a）对 现代概念性AUD病因学框架（包括ANA）阐述的模型，以及（B）推导出 使用客观原则开发的基于机制的AUD计算机化自适应测试（CAT）评估 测试建设和社区参与式研究战略。一、考生自述集 项目索引13个病因学领域阐述了病因学，理论为基础的，个体发生层次（ETOH） AUD机制的框架，作为AARDoC/ANA的最新扩展，将从 文献和两轮认知访谈将被用来完善一个不同的群体之间的项目集， 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组合 社区和临床样本（N = 1，200），以实证检验项目结构并确定最佳拟合 模型项目反应理论将被用来校准项目的目的是建立一个CAT为每个 在所识别的域中（例如，奖励，认知控制，消极情绪）。使用经过改进和校准的 项目集和特定领域的CAT，数据将收集从一个额外的独立样本的沉重 饮酒者（N = 100）。还将进行为期14天的生态瞬时评估和后续评估， 进行的目标是评估在生态有效的背景下的CAT的心理测量特性， 随着时间具体地，为了确定特定于域的CAT是否证明有效性（例如，收敛， 判别的，预测的）和可靠性（例如，在不同患者人群和性别/性别中进行的试验 组所有的研究目标将与有生活经验的个人一起进行，并与他们协商。 澳元，以确保该措施是可接受的，可行的，并充分的背景。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 （改善AUD的诊断和跟踪）。由此产生的措施也有可能支持取得进展 通过促进对机制的评估， 可作为AUD治疗的可行靶点，包括行为和药理学干预。

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.