The neural mechanisms of risk for alcohol use disorder among college students

大学生酒精使用障碍风险的神经机制

基本信息

批准号：
10237328
负责人：
Amanda L Elton
金额：
$ 15.4万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10237328
关键词：
21 year old Adolescent Adult Affect Affective Age Alcohol abuse Alcohol consumption Alcoholism Analysis of Covariance Applications Grants Behavior Behavioral Biological Markers Brain Brain region Characteristics Child Child Abuse and Neglect Childhood Cognitive Complex Data Data Analyses Decision Making Development Disease Elderly Enrollment Environmental Risk Factor Epidemiology Equation Family history of Female Foundations Functional Magnetic Resonance Imaging Future Genetic Genetic Predisposition to Disease Genetic Risk Growth Heritability Impulsive Behavior Impulsivity Incidence Individual Individual Differences Investigation Knowledge Link Measures Mediating Mediator of activation protein Mentors Methodology Modeling Motor Neurobiology Neurosciences Participant Pathologic Pathway interactions Patient Self-Report Pattern Performance Phenotype Predisposition Prevention strategy Publications Recording of previous events Reporting Research Research Project Grants Rewards Risk Risk Factors Role Sex Differences Signal Transduction Stress Structure Surveys Testing Time TimeLine Training addiction alcohol misuse alcohol risk alcohol use disorder base behavior measurement cognitive neuroscience design discounting disorder risk drinking drinking behavior early life stress emerging adult endophenotype experience follow-up functional MRI scan longitudinal analysis male neglect neural network neuroimaging neuroimaging marker neuromechanism pediatric trauma population based recruit relating to nervous system research study response sex support network symposium training project underage drinking university student

项目摘要

PROJECT SUMMARY/ABSTRACT Individuals with a history of childhood trauma are at an increased risk of developing an alcohol use disorder (AUD), a susceptibility that is further enhanced if they have a family history of this disorder. In fact, approximately 50% of the risk for developing an alcohol use disorder (AUD) is driven by genetic factors. Thus, evidence suggests that both genetic and environmental risk factors contribute to AUD and that these factors likely exert combined effects. However, the neural mechanisms by which these risk factors contribute to the development of AUD are not yet understood. Research in individuals with a family history of AUD suggests that this genetic predisposition produces increased behavioral impulsivity. Previous research in victims of childhood maltreatment has likewise identified cognitive and affective consequences of childhood stress, including increased impulsivity. It is noteworthy that impulsive behavior is not only characteristic of individuals with a current AUD, but is also a predictor later life alcohol use among adolescents, suggesting these behaviors precede the development of AUD. This proposed training and research study are built on the hypothesis that impulsivity functions as an intermediate phenotype that mediates the relationship between genetic and environmental risk factors for AUD and problem drinking. The training project will focus on two domains of impulsivity – discounting of delayed rewards and response inhibition – based on strong evidence supporting their link to both AUD and its risk factors. The first Aim will include a neuroimaging investigation of the these two tasks of impulsivity and an examination of the large-scale neural network correlates of risk factors for AUD. Longitudinal analyses (Aim 2) will examine the predictive relationship between neural measures of impulsivity on these tasks and changes in alcohol consumption over a three year follow-up timeline. Finally, Aim 3 is dedicated to examining the sex-dependent neural alterations associated with risk for AUD and well as sex-dependent relationships between the brain and alcohol use trajectories. The candidate’s prior training in the neurodevelopmental consequences of childhood trauma, cognitive neuroscience of addiction, sex differences, advanced statistical approaches, and neuroimaging methodologies provide a strong foundation for the proposed research project. The proposed training experiences will fill additional gaps through a combination of mentoring, didactic coursework, seminars, and conferences. The training plan is particularly tailored to provide additional support in alcoholism research and provides an extension into the study of addiction genetics. The training experience will be led by Dr. Charlotte Boettiger, an expert in behavioral and neuroimaging biomarkers of addiction, and supported by co-mentors Dr. Fulton Crews, an expert in the neurobiology of AUD, and Dr. Kirk Wilhelmsen, an expert in addiction genetics. The completion of this training will provide a strong foundation enabling the candidate to pursue independent research and will provide adequate knowledge, publications, and pilot data to be competitive for future grant applications focused on elucidating the neural basis of risk for AUD.

项目概要/摘要有童年创伤史的人患酒精使用障碍的风险增加（AUD），如果他们有这种疾病的家族史，那么易感性会进一步增强。因此，有证据表明，50% 的酒精使用障碍 (AUD) 风险是由遗传因素驱动的。表明遗传和环境风险因素都会影响 AUD，并且这些因素可能会发挥作用然而，这些风险因素促进发育的神经机制。对有 AUD 家族史的个体的研究表明，这种遗传因素对 AUD 的影响尚不清楚。先前对儿童虐待受害者的研究表明，这种倾向会增加行为冲动。同样也发现了童年压力对认知和情感的影响，包括冲动的增加。值得注意的是，冲动行为不仅是持有当前澳元的个人的特征，而且也是一种行为。预测青少年以后生活中饮酒的情况，表明这些行为先于青少年的发展 AUD。这项拟议的培训和研究是建立在冲动作为一种因素的假设之上的。介导 AUD 遗传和环境风险因素之间关系的中间表型培训项目将重点关注冲动的两个领域——延迟的折扣。奖励和反应抑制——基于强有力的证据支持它们与澳元及其风险因素的联系。第一个目标将包括对冲动这两项任务的神经影像学研究和检查大规模神经网络的 AUD 风险因素相关性将进行纵向分析（目标 2）。这些任务的冲动性神经测量与酒精变化之间的预测关系最后，目标 3 致力于检查性别依赖性。与 AUD 风险相关的神经改变以及大脑和大脑之间的性别依赖性关系候选人之前接受过的关于童年神经发育后果的培训。创伤、成瘾认知神经科学、性别差异、先进的统计方法，以及神经影像方法为拟议的研究项目提供了坚实的基础。培训经验将通过指导、教学课程、研讨会、培训计划专门为酗酒研究提供额外支持。并提供成瘾遗传学研究的延伸。培训经验将由夏洛特博士领导。 Boettiger 是成瘾行为和神经影像生物标志物方面的专家，并得到了共同导师 Dr. Boettiger 的支持。 AUD 神经生物学专家 Fulton Crews 和成瘾遗传学专家 Kirk Wilhelmsen 博士。完成本次培训将为候选人追求独立提供坚实的基础研究并将提供足够的知识、出版物和试点数据，以便在未来的资助中具有竞争力应用的重点是阐明澳元风险的神经基础。