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

项目总结/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，这种易感性会进一步增强。事实上， 50%的酒精使用障碍（AUD）风险由遗传因素驱动。因此，证据 表明遗传和环境风险因素都有助于AUD，并且这些因素可能发挥作用。 综合效应。然而，这些危险因素促进发展的神经机制 目前还不了解。对有AUD家族史的个体的研究表明，这种遗传 易感性会增加行为冲动。先前对儿童虐待受害者的研究 同样也发现了童年压力的认知和情感后果，包括冲动性的增加。 值得注意的是，冲动行为不仅是目前持有澳元的人的特征， 预测青少年晚年饮酒，这表明这些行为先于青少年的发展。 澳元。这项拟议的培训和研究是建立在冲动性作为一种功能的假设之上的。 介导AUD遗传和环境风险因素之间关系的中间表型 还有酗酒问题该培训项目将集中在两个领域的冲动-折扣延迟 奖励和反应抑制-基于强有力的证据支持它们与AUD及其风险因素的联系。 第一个目标将包括神经影像调查这两个任务的冲动和检查 大规模神经网络与AUD风险因素的相关性。纵向分析（目标2）将检查 这些任务的神经冲动性测量与酒精变化之间的预测关系 在三年随访时间轴内的消耗量。最后，目标3致力于研究性别依赖 与AUD风险相关的神经改变以及大脑和 酒精使用轨迹候选人在儿童时期神经发育后果方面的先前培训 创伤，成瘾的认知神经科学，性别差异，先进的统计方法， 神经影像学方法为拟议的研究项目提供了坚实的基础。拟议 培训经验将通过指导、教学课程、研讨会 和会议。该培训计划是专门为酗酒研究提供额外的支持 并为成瘾遗传学的研究提供了延伸。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，他的共同导师Dr。 AUD神经生物学专家富尔顿克鲁斯和成瘾遗传学专家柯克威廉姆森博士。 完成这项培训将提供一个坚实的基础，使候选人能够追求独立 研究，并将提供足够的知识，出版物和试点数据，以竞争未来的赠款 应用程序集中于阐明AUD风险的神经基础。

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.