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

项目摘要/摘要 有童年创伤病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，大约 50%的酒精使用障碍(AUD)风险是由遗传因素驱动的。因此，证据 这表明遗传和环境风险因素都会导致AUD，而且这些因素可能会对 综合效应。然而，这些风险因素促进发育的神经机制 对澳元的影响尚不清楚。对有澳门氏症家族史的个体的研究表明，这种基因 易感性会增加行为冲动。关于儿童期虐待受害者的先前研究 同样确定了童年压力的认知和情感后果，包括增加的冲动。 值得注意的是，冲动行为不仅是当前AUD患者的特征，而且也是一种 青少年晚年饮酒的预测指标，表明这些行为先于 澳元。这项拟议的培训和研究研究建立在这样的假设之上，即冲动作为一种 中介AUD遗传和环境风险因素关系的中间表型 还有酗酒问题。培训项目将集中在冲动的两个领域--延迟打折 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个任务的神经成像调查和检查 对AUD的相关危险因素进行大规模神经网络分析。纵向分析(目标2)将检查 在这些任务中冲动的神经测量与酒精变化之间的预测关系 在三年的跟踪时间线上消费。最后，目标3致力于研究性别依赖者 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关系 酒精使用轨迹。应聘者先前接受的儿童神经发育后果方面的培训 创伤，成瘾的认知神经科学，性别差异，先进的统计方法，以及 神经成像方法为拟议的研究项目提供了坚实的基础。建议数 培训经验将通过指导、授课课程、研讨会、 和会议。培训计划特别为酒精中毒研究提供额外的支持 为成瘾遗传学的研究提供了一种延伸。培训体验将由夏洛特博士带队 BoetTiger博士是一位行为和神经成像成瘾生物标志物方面的专家，并得到了共同导师Dr。 AUD神经生物学专家Fulton Crews和成瘾遗传学专家Kirk Wilhelmsen博士。 完成这项培训将为候选人追求独立奠定坚实的基础 并将提供足够的知识、出版物和试点数据，以便在未来的拨款中具有竞争力 应用重点在于阐明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.