Determining the Contributions of Four AARDoC Functional Domains to the Etiology of Heavy Drinking and AUD Symptoms: A Prospective, Multimodal Approach

确定四个 AARDoC 功能域对重度饮酒和 AUD 症状病因学的贡献：前瞻性、多模式方法

• 批准号: 10607017
• 负责人: BRUCE D BARTHOLOW
• 金额: $ 72.93万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10607017
• 关键词: Acceleration; Accounting; Adolescence; Adolescent; Affect; Age; Alcohol consumption; Alcohol dependence; Anxiety; Behavioral; Consumption; Data Collection; Data Set; Development; Diagnosis; Disinhibition; Ecology; Enrollment; Etiology; Failure; Female; Goals; Heavy Drinking; Heterogeneity; Impairment; Individual; Individual Differences; Intervention; Knowledge; Lifestyle-related condition; Link; Maps; Measures; Modality; Modeling; Outcome; Participant; Patient Self-Report; Pattern; Persons; Phenotype; Play; Process; Prospective Studies; Research; Research Domain Criteria; Research Personnel; Rewards; Risk; Role; Sampling; Severities; Shapes; Social Environment; Suggestion; Symptoms; Testing; Time; Typology; Work; addiction; alcohol effect; alcohol exposure; alcohol involvement; alcohol use disorder; cognitive control; cohort; data structure; design; disease classification; drinking; emerging adult; emerging adulthood; incentive salience; indexing; individualized prevention; longitudinal design; multimodality; neuroadaptation; neurobehavioral; neurophysiology; personalized intervention; personalized medicine; prospective; psychologic; social; symptom cluster; theories; treatment strategy

PROJECT SUMMARY / ABSTRACT Alcohol use disorder (AUD) is highly heterogeneous in that its symptoms are highly varied and, often, non- overlapping across individuals. In theory, this phenotypic heterogeneity reflects the influence of multiple underlying causes, or etiologic mechanisms. This etiologic complexity makes AUD treatment very challenging; researchers have identified AUD’s etiologic complexity as the most critical barrier to progress in developing more effective, personalized treatments. Addiction theorists have identified a set of alcohol addiction research domain criteria (AARDoC) functional domains, believed to be important etiologic mechanisms for AUD. Yet, existing models meant to link these mechanisms to AUD-related behaviors and symptoms fail to consider etiology. Hence, many basic questions concerning the etiology of problematic drinking and AUD-related symptoms remain unresolved. The proposed work aims to identify the prospective contributions of functional domain neuro- behavioral indicators to the etiology of heavy drinking (HD) and AUD-related symptoms during adolescence and emerging adulthood, the decade of development when HD and AUD-related symptoms are most prevalent. We will enroll a target sample of 480 adolescents and emerging adults (160 in each of three partially overlapping age cohorts [50% female], pre-screened for elevated HD risk) to participate in a prospective study using an accelerated longitudinal design, which will allow us to characterize trajectories of alcohol involvement and AUD- related symptoms over a 10-year period of development within a five-year study. We will use a neuroclinical assessment approach to comprehensively characterize four functional domains—cognitive control/disinhibition (DIS), reward sensitivity (RS), anxiety (ANX), and incentive salience (IS)—using validated and reliable self- report, behavioral, and neurophysiological measures during each of three waves of data collection (15 months apart). Alcohol involvement, AUD-related symptoms, and social-environment factors will be assessed at 5-month intervals. Using this multi-wave, multimodal approach, we will address three specific aims: (1) characterize the influence of the functional domains on the etiology of alcohol involvement; (2) accounting for the influence of alcohol involvement, characterize the influence of the functional domains on the etiology of AUD-related symptoms; and (3) characterize the influence of HD on functional domain neurobehavioral indicators. Analyses will characterize how various combinations of domain indicators affect latent states of alcohol involvement (volume of consumption; patterns of use) and AUD-related symptoms (numbers of symptoms; clusters of symptoms) and transitions across latent states over time. This work will produce a unique and rich dataset, and its findings will directly inform the development of personalized intervention and treatment strategies that can be deployed to target the functioning of specific domains during periods when their influence is greatest.

项目总结/摘要 酒精使用障碍（AUD）是高度异质性的，因为它的症状是高度多样化的，而且通常是非特异性的。 在个体之间重叠。从理论上讲，这种表型异质性反映了多重遗传因素的影响。 根本原因或病因机制。这种病因的复杂性使得AUD治疗非常具有挑战性; 研究人员已经确定AUD的病因复杂性是发展更多 有效的个性化治疗成瘾理论家已经确定了一套酒精成瘾研究领域 标准（AARDoC）功能域，被认为是AUD的重要病因学机制。然而，现有 旨在将这些机制与AUD相关行为和症状联系起来的模型未能考虑病因。 因此，许多关于问题性饮酒和AUD相关症状的病因学的基本问题仍然存在 悬而未决拟议的工作旨在确定功能域神经元的潜在贡献， 青少年时期大量饮酒（HD）和AUD相关症状的病因学行为指标， 成年期，HD和AUD相关症状最普遍的十年发展期。我们 将招募480名青少年和新生儿（三个部分重叠的研究中各160名）作为目标样本 年龄队列[50%女性]，预先筛选HD风险升高）参加一项前瞻性研究， 加速纵向设计，这将使我们能够描述酒精参与和AUD的轨迹， 在一项为期五年的研究中，在10年的发展期内出现相关症状。我们将使用神经临床 综合表征认知控制/去抑制四个功能域的评估方法 (DIS)，奖励敏感性（RS），焦虑（ANX）和激励显着性（IS）-使用验证和可靠的自我- 在三波数据收集（15个月）中的每一波期间进行报告、行为和神经生理学测量 分开）。将在5个月时评估酒精参与、AUD相关症状和社会环境因素 的间隔使用这种多波，多模态方法，我们将解决三个具体目标：（1）表征 功能域对酒精参与病因学的影响;（2）解释 酒精参与，表征功能域对AUD相关病因的影响 症状;（3）表征HD对功能域神经行为指标的影响。分析 将描述领域指标的各种组合如何影响酒精参与的潜在状态 （消费量;使用模式）和AUD相关症状（症状数量; 症状）和随时间跨越潜伏状态的转换。这项工作将产生一个独特而丰富的数据集， 其研究结果将直接为个性化干预和治疗策略的发展提供信息， 在特定领域的影响力最大的时期，针对这些领域的运作进行部署。