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

项目概要/摘要 酗酒是一个日益严重的公共卫生问题，通常始于青春期/年轻时 成年典型的大脑成熟模式，其中情感和奖励相关区域优先于 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。酒精参与程度的结果，从个人 基因组赋予的脑发育和相关行为表型和/或修饰的差异 神经轨迹和行为尚不清楚。纵向的、遗传学方面的研究可以解决这些问题 通过研究酒精参与的发展轨迹和相关的风险和后果的问题。 本研究的主要目的是研究：（a）是否多基因脆弱性，以阶段为基础的 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）从童年后期到成年早期，和（B）的程度， 这些行为和神经指标与酒精参与的阶段共享基因组责任。通过 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 与特异质的优势，以及几个基因组侧关联研究酒精参与，大脑 结构和行为，这种多模式，跨学科的调查旨在产生新的见解， 生物学和行为机制的基础和处理与酒精参与轨迹。结果 有可能告知青少年和年轻人的病因学概念化 成人酒精参与和改善预防和治疗以及相关的政策和教育 努力本项目的实现将通过以下培训目标来实现：（1）培养专业人才 关于酒精参与和相关大脑结构和行为的知识，（2）提高 高级定量（例如，纵向）分析，（3）获得尖端基因组方法学的培训，（4） 提高对结构神经影像学方法的熟悉程度，以及（5）促进专业发展， 申请人的职业发展是独立的，NIH资助的学术研究人员。培训 协助申请人实现这些目标的团队在酒精使用方面具有丰富的专业知识 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 发展促进她的研究计划和职业生涯所需的表型，分析和专业能力 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.