Integrating longitudinal research on adolescent AUDs with imaging and genetics

将青少年 AUD 的纵向研究与影像学和遗传学相结合

• 批准号: 8197682
• 负责人: Tammy Chung
• 金额: $ 8.66万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197682
• 关键词: Abstinence; Addictive Behavior; Adolescence; Adolescent; Adult; Adverse effects; Affect; African American; Aftercare; Age; Alcohol abuse; Alcohol consumption; Alcohol or Other Drugs use; Alcohols; Alleles; Anisotropy; Anxiety; Applications Grants; Area; Behavioral; Biological Markers; Brain; Candidate Disease Gene; Cannabis; Catechol O-Methyltransferase; Caucasians; Caucasoid Race; Chronic; Classification; Clinical; Collaborations; Collection; Communities; DNA; DRD4 gene; Data; Data Collection; Development; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Disease remission; Dopamine Receptor; Environment; Environmental Risk Factor; Esthesia; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Genes; Genetic; Genetic Polymorphism; Genotype; Heavy Drinking; Image; Image Analysis; Independent Scientist Award; Individual; Inferior; Intervention; Knowledge; Lead; Link; Literature; Maintenance; Marijuana Smoking; Measures; Mediating; Mental Depression; Metabolic Pathway; Methods; Methyltransferase Gene; Modeling; Molecular; Neurocognitive; Nicotine; Outcome; Outpatients; Parents; Pathway interactions; Pharmaceutical Preparations; Phase; Phenotype; Prefrontal Cortex; Preparation; Preventive Intervention; Process; Protocols documentation; Public Health; Readiness; Reading; Recovery; Recruitment Activity; Recurrence; Relapse; Research; Rewards; Risk; Saliva; Sampling; Severities; Structure; Substance Use Disorder; Supervision; Symptoms; System; Technology; Teenagers; Testing; Time; Training; Training Activity; Training Support; Treatment outcome; Variant; Work; Writing; Youth; addiction; adolescent alcohol; adolescent substance use; adolescents with alcohol use disorders; alcohol involvement; alcohol research; base; career development; cognitive function; early onset substance use; effective therapy; executive function; follow-up; genetic analysis; genetic association; improved; informant; neuroimaging; peer; programs; public health relevance; receptor function; response; serotonin transporter; skills; substance abuse treatment; task analysis; treatment response; trial comparing; valylvaline; white matter; young adult

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.

该K02独立科学家奖申请提出了功能磁共振成像（fMRI）和候选基因分析的结构化职业发展活动，特别是为了确定导致和维持青少年物质使用的基因，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基于仔细的临床描述，但越来越多的遗传学和神经成像技术可以帮助验证和完善，甚至可能重组，成瘾核心过程的概念模型，如对物质使用的“控制受损”。职业发展活动将建立在申请人在青少年物质使用障碍的分类和过程中的专业知识，并将集中在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的知识和技能，在功能磁共振成像（应用于一个antisaccade任务）和选定的候选基因的分析，将提供有效的合作与神经影像学和遗传学专家的基础，以便将这些方法整合到纵向研究。在fMRI分析的职业发展活动将被应用到数据的背景下，奖励，反应抑制的敏感措施，已收集在R01“课程的酒精和药物的问题，在治疗青年”（课程研究）的一个antisaccade任务。职业发展活动中的候选基因分析将应用于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fMRI antisaccade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，这些表型可能预测治疗反应。在功能磁共振成像和候选基因分析的实践培训将补充教程与K02顾问，定向阅读，和课程工作。K02奖的支持将为申请人提供受保护的时间，以推进关于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计划，该计划可用于指导有效治疗的发展。 公共卫生关系：很少有涉及青少年的研究整合了神经影像学和遗传学数据，以检查药物使用早期发作的风险，药物使用轨迹和对治疗的不同反应。在青少年药物使用研究中整合神经影像学和遗传学方法对确定可用于改善向青年提供的预防和干预工作的时间和内容的生物标志物具有重大的公共卫生意义。