Trajectories of Alcohol Involvement from Middle Childhood to Early Adulthood: A Multimodal Investigation

项目摘要/摘要 有问题的饮酒是一个日益严重的公共卫生问题，通常始于青春期/青年 成人期。典型的大脑成熟模式，其中与情绪和奖励相关的区域优先于 那些与认知控制和调节有关的基因与酒精参与的发育风险有关 以及酒精的神经毒性作用。个人在多大程度上参与酒精活动 基因授予的大脑发育以及相关行为表型和/或修饰的差异 神经轨迹和行为尚不清楚。纵向的遗传信息研究可以解决这些问题 通过检查酒精参与的发展轨迹以及相关的风险和后果来提出问题。 这项调查的主要目的是检查：(A)基于阶段的多基因易感性是否 行为和结构神经表型与酒精参与的轨迹有关(即，启动， 升级、有问题的使用、停止使用)从儿童期后期到成年期，以及(B) 这些行为和神经指标与酒精参与的阶段有共同的基因组风险。穿过 使用最先进的基因组技术和整合三个动力良好的纵向数据集 除了几项与酒精有关的基因组方面的关联研究外，大脑还具有独特的优势 结构和行为，这项多模式的跨学科调查旨在产生关于以下方面的新见解 酒精参与轨迹背后的生物学和行为机制以及与之相关的机制。结果 从拟议的项目中有可能为青少年和青少年的病因概念化提供信息 成人酗酒和改善预防和治疗以及相关政策和教育 努力。该项目的实现将通过以下培训目标来实现：(1)获取专家 有关饮酒及相关的脑结构和行为的知识，(2)促进 推进定量(如纵向)分析，(3)接受尖端基因组方法学方面的培训，(4) 增加对结构神经成像方法的熟悉，以及(5)促进专业发展，如 申请者将成为一名独立的、由NIH资助的学术研究人员。培训 为帮助申请人实现这些目标而组建的团队在酒精使用方面拥有丰富的专业知识 轨迹、大脑结构、纵向和基因组技术。在他们的支持下，申请人将 发展表型、分析和专业能力，以促进她的研究计划和职业生涯 野心。

Project Summary/Abstract Problematic alcohol use is a growing public health concern that typically begins during adolescence/young adulthood. Typical brain maturation patterns wherein emotion- and reward-related regions are prioritized over those relevant to cognitive control and regulation have been linked to developmental risk for alcohol involvement as well as neurotoxic effects of alcohol. The extent to which alcohol involvement results from individual differences in genomically-conferred brain development and related behavioral phenotypes and/or modifies neural trajectories and behavior is not clear. Longitudinal, genetically informed research can address these questions by examining developmental trajectories of alcohol involvement and related risks and consequences. The overarching aim of this investigation is to examine: (a) whether polygenic vulnerability to stage-based behavioral and structural neural phenotypes are related to trajectories of alcohol involvement (i.e., initiation, escalation, problematic use, desistance) from late childhood through young adulthood, and (b) the extent to which these behavioral and neural indicators share genomic liability with stages of alcohol involvement. Through the use of state-of-the-art genomic techniques and the integration of three well-powered, longitudinal datasets with idiosyncratic strengths alongside several genome-side association studies of alcohol involvement, brain structure, and behavior, this multimodal, interdisciplinary investigation aims to yield novel insights about biological and behavioral mechanisms underlying and transacting with alcohol involvement trajectories. Results from the proposed project have the potential to inform the etiologic conceptualization of adolescent and young adult alcohol involvement and improve prevention and treatment as well as relevant policy and educational efforts. The realization of this project will be achieved through the following training goals: (1) to acquire expert knowledge about alcohol involvement and related brain structure and behavior, (2) to promote competence in advance quantitative (e.g., longitudinal) analysis, (3) to gain training in cutting-edge genomic methodology, (4) to augment familiarity with methods of structural neuroimaging, and (5) to promote professional development as the applicant progresses toward a career as an independent, NIH-funded academic researcher. The training team assembled to assist the applicant in achieving these goals has substantial expertise in alcohol use trajectories, brain structure, and longitudinal and genomic techniques. With their support, the applicant will develop the phenotypic, analytic, and professional aptitude needed to foster her research program and career ambitions.