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.

项目摘要 /摘要 酒精使用障碍（AUD）是高度异质的，因为它的症状高度多样，而且通常非 - 重叠个人。从理论上讲，这种表型异质性反映了多重的影响 基本原因或病因机制。这种病因复杂性使AUD治疗非常挑战。 研究人员已经确定AUD的病因复杂性是发展更多进展的最关键的障碍 有效的个性化治疗。成瘾理论家已经确定了一组酒精成瘾研究领域 标准（AARDOC）功能域，被认为是AUD的重要病因机制。但是，存在 旨在将这些机制与听众相关的行为和症状联系起来的模型无法考虑病因。 因此，关于有问题的饮酒和与听众相关症状的病因的许多基本问题仍然存在 未解决。拟议的工作旨在确定功能领域神经的前瞻性贡献 在青少年和 新兴的成年，当高清和与音频相关的符号最普遍时的发展十年。我们 将招募480名青少年和新兴成年人的目标样本（三个部分重叠的每个成年人中有160个 年龄队列[50％女性]，预先筛选高清风险的升级），以使用 加速的纵向设计，这将使我们能够表征酒精参与和听觉的轨迹 在一项为期五年的研究中，相关症状在10年的发展期内。我们将使用神经词 评估方法全面表征四个功能域 - 认知控制/抑制 （dis），奖励灵敏度（RS），焦虑（ANX）和激励显着性（IS） - 造成经过验证且可靠的自我 报告，行为和神经生理学措施在三个数据收集中的每一波中（15个月） 分开）。酒精参与，与AUD相关的症状和社会环境因素将在5个月以来评估 间隔。使用这种多波，多模式的方法，我们将解决三个具体目标：（1）表征 功能领域对酒精参与病因的影响； （2）考虑 酒精参与，表征功能域对AUD相关的病因的影响 症状; （3）表征HD对功能域神经行为指标的影响。分析 将表征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）和与音频相关的符号（符号数量； 随着时间的流逝，症状）和潜在状态之间的过渡。这项工作将产生一个独特而丰富的数据集，并且 它的发现将直接告知个性化干预和治疗策略的发展 部署以针对特定域的功能在其影响最大时的功能。