Integrating longitudinal research on adolescent AUDs with imaging and genetics

描述(由申请者提供)：这份K02独立科学家奖申请书建议在功能磁共振成像(FMRI)和候选基因分析方面开展有组织的职业发展活动，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。目前对物质使用障碍的分类系统是建立在仔细的临床描述基础上的，但遗传学和神经成像方面日益可用的技术可以帮助验证和完善，甚至可能重新构建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者在青少年物质使用障碍的分类和病程方面的专业知识为基础，并将重点放在两个关键的成瘾结构上：反应抑制和奖励敏感性。拟议职业发展活动的目的是增加应聘者在功能磁共振成像(应用于防眼跳任务)和分析选定的候选基因方面的知识和技能，这将为与神经成像和遗传学专家进行有效协作奠定基础，以便将这些方法纳入纵向研究。功能磁共振成像分析中的职业发展活动将应用于在R01“接受治疗的青年中的酒精和药物问题课程”(课程研究)中收集的奖励背景下的反眼跳任务的数据，这是反应抑制的一种敏感措施。职业发展活动中的候选基因分析将应用于在课程研究和匹兹堡青少年酒精研究中心收集的遗传数据。在课程研究中收集的功能磁共振抗眼跳和候选基因数据的综合分析方面的培训将用于确定与可能预测治疗反应的神经认知表型的遗传关联。功能磁共振成像和候选基因分析方面的实践培训将由K02顾问的教程、定向阅读材料和课程工作补充。K02奖项的支持将为申请者提供受保护的时间，以推进一项关于青少年药物使用者发病、病程和治疗反应潜在的遗传、神经认知和环境因素的酒精研究计划，该计划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.