Integrating longitudinal research on adolescent AUDs with imaging and genetics

描述（由申请人提供）：这项K02独立科学家奖申请提出了功能性磁共振成像（fMRI）和候选基因分析的结构化职业发展活动，特别是确定导致和维持青少年药物使用的基因，大脑活动和环境因素之间的联系。目前物质使用障碍的分类系统是基于仔细的临床描述，但遗传学和神经影像学方面日益可用的技术可以帮助验证和完善，甚至可能重构成瘾的核心过程的概念模型，例如对物质使用的“控制受损”。职业发展活动将以申请人在青少年物质使用障碍的分类和过程方面的专业知识为基础，并将侧重于两个关键的成瘾结构：反应抑制和奖励敏感性。拟议的职业发展活动的目的是增加候选人在功能磁共振成像（应用于反扫视任务）和选定的候选基因分析方面的知识和技能，这将为与神经成像和遗传学专家有效合作提供基础，以便将这些方法整合到纵向研究中。功能磁共振成像分析中的职业发展活动将应用于奖励背景下的反扫视任务数据，奖励是反应抑制的一种敏感措施，这些数据已收集在R01“接受治疗的青年酒精和药物问题课程”（课程研究）中。候选基因分析中的职业发展活动将应用于课程研究和匹兹堡青少年酒精研究中心收集的基因数据。课程研究中收集的fMRI抗扫视和候选基因数据的综合分析培训将用于识别与神经认知表型的遗传关联，从而预测治疗反应。在fMRI和候选基因分析方面的实践培训将辅以K02顾问的教程、指导阅读和课程作业。该K02奖的支持将为申请人提供受保护的时间，以推进青少年物质使用者发病、病程和治疗反应的遗传、神经认知和环境因素的酒精研究项目，这些研究可用于指导有效治疗的发展。

DESCRIPTION (provided by applicant): This K02 Independent Scientist Award application proposes structured career development activities in functional magnetic resonance imaging (fMRI) and candidate gene analyses, specifically to identify links between genes, brain activity, and environmental factors that lead to and maintain adolescent substance use. Current systems of classification for substance use disorders are based on careful clinical description, but increasingly available technologies in genetics and neuroimaging can help to validate and refine, possibly even restructure, conceptual models of core processes underlying addiction, such as "impaired control" over substance use. Career development activities will build on the applicant's expertise in the classification and course of adolescent substance use disorders, and will focus on two key addiction constructs: response inhibition and reward sensitivity. The aim of the proposed career development activities is to increase the candidate's knowledge and skills in fMRI (applied to an antisaccade task) and the analysis of selected candidate genes that will provide the foundation for effective collaboration with experts in neuroimaging and genetics in order to integrate these methods into longitudinal research. Career development activities in fMRI analysis will be applied to data from an antisaccade task in the context of reward, a sensitive measure of response inhibition, that have been collected in the R01 "Course of alcohol and drug problems in treated youth" (Course Study). Career development activities in the analysis of candidate genes will be applied to genetic data collected in the Course Study, and the Pittsburgh Adolescent Alcohol Research Center. Training in the integrated analysis of fMRI antisaccade and candidate gene data collected in the Course Study will be used to identify genetic associations with a neurocognitive phenotype that may predict treatment response. Hands-on training in fMRI and candidate gene analyses will be supplemented by tutorials with K02 consultants, directed readings, and course work. Support from this K02 award will provide the applicant with protected time to advance a program of alcohol research on genetic, neurocognitive, and environmental factors underlying onset, course, and response to treatment in adolescent substance users, which can be used to guide the development of effective treatment. PUBLIC HEALTH RELEVANCE: Few studies involving adolescents have integrated neuroimaging and genetic data to examine risk for early onset of substance use, substance use trajectories, and differential response to treatment. Integration of neuroimaging and genetic approaches in studies of adolescent substance use has substantial public health implications for identifying biomarkers that can be used to improve the timing and content of prevention and intervention efforts provided to youth.