Genetic and Neural Factors in Alcohol-Influenced Aggression

项目摘要/摘要 这份K01指导研究科学家发展奖提案旨在为David Chester博士提供 为推进他成为独立人士的职业目标所需的培训和研究经验 酒精调查员。他追求这一职业目标是为了更好地理解和干预生物 酒精影响攻击的基础(即遗传风险因素、神经机制)。该项目中的活动 该提案将以切斯特博士在攻击性心理和神经基础方面的现有技能为基础 行为。 培训计划：切斯特博士寻求先进基因技术和酒精滥用表型方面的培训， 这将通过一个结构化的培训计划来实现，该计划包括定期与导师会面，两个 外部实验室轮换，课程作业和一个统计遗传学研讨会，定向阅读，和两个 实验室旋转。切斯特博士的培训计划利用了杰出的研究和教育 在弗吉尼亚联邦大学(VCU)环境研究中心，由知名专家团队担任导师。他的 主要导师是Danielle Dick博士(酒精滥用和相关的遗传风险因素方面的专家 外化行为)。切斯特博士还将由大卫·戈德曼博士(专家)共同指导 酒精滥用及其相关外化行为的遗传和神经基础)，Fazil Aliev博士(专家 统计遗传学)，多米尼克·帕罗特博士(酒精影响的攻击行为的专家)，以及F·杰拉德博士 默勒(酒精滥用及其相关外化行为的神经基础方面的专家)。 研究计划：K01提案的科学目标是检查易患遗传因素 某些人在酒精滥用的情况下采取咄咄逼人的行动。此外，我们计划调查 将这些遗传风险因素与实际的酒精影响的攻击行为联系起来的神经机制。遗传 酒精影响的攻击性的风险因素将通过分析现有的数据进行测试，这些数据来自[五个NIH资助的 公开可用的基因组数据集]和来自VCU的NIAAA资助的Spit4Science的一个新样本 该项目调查了本科生的纵向酒精滥用轨迹。去调查 神经机制，Spit4Science参与者的一个子样本将被招募参加一项研究，该研究将 将安慰剂控制的酒精注射、实验室攻击措施和大脑功能相结合 成像(FMRI)。这项拟议的研究是第一次系统地研究人的遗传基础 酒精影响的攻击性，严重威胁公共健康。此外，这可以识别神经通路 这些遗传效应，可以为心理和药物干预提供信息，这可能证明 在减少酒精滥用的暴力后果方面卓有成效。这一奖项将支持这些目标，并 推进NIAAA的战略计划，以确定酒精滥用和随后恢复的潜在机制。

PROJECT SUMMARY/ABSTRACT This K01 Mentored Research Scientist Development Award proposal seeks to provide Dr. David Chester with the training and research experiences necessary to advance his career goal of becoming an independent alcohol investigator. He seeks this career goal in order to better understand and intervene upon the biological bases (i.e., genetic risk factors, neural mechanisms) of alcohol-influenced aggression. The activities in this proposal will build upon Dr. Chester's existing skillset in the psychological and neural bases of aggressive behavior. Training plan: Dr. Chester seeks training in advanced genetic techniques and alcohol misuse phenotypes, which will be achieved through a structured training plan that consists of regular meetings with mentors, two external laboratory rotations, coursework and a workshop in statistical genetics, directed readings, and two laboratory rotations. Dr. Chester's training plan leverages the outstanding research and educational environment at Virginia Commonwealth University (VCU) with a team of renowned experts as mentors. His primary mentor is Dr. Danielle Dick (an expert in genetic risk factors for alcohol misuse and associated externalizing behaviors). Dr. Chester will also be co-mentored by Dr. David Goldman (an expert on the genetic and neural basis of alcohol misuse and associated externalizing behaviors), Dr. Fazil Aliev (an expert in statistical genetics), Dr. Dominic Parrot (an expert in alcohol-influenced aggression), and Dr. F. Gerard Moeller (an expert in the neural basis of alcohol misuse and associated externalizing behaviors). Research plan: The scientific objective of this K01 proposal is to examine the genetic factors that predispose certain individuals to act aggressively in the context of alcohol misuse. Further, we plan to investigate the neural mechanisms that link these genetic risk factors to actual acts of alcohol-influenced aggression. Genetic risk factors for alcohol-influenced aggression will be tested by analyzing existing data from [five NIH-funded publicly-available genomic datasets] and a new sample collected from VCU's NIAAA-funded Spit4Science project, which investigates longitudinal alcohol misuse trajectories among undergraduates. To investigate neural mechanisms, a sub-sample of the Spit4Science participants will be recruited for a study that will combine a placebo-controlled alcohol administration, laboratory aggression measures, and functional brain imaging (fMRI). This proposed research is the first systematic investigation of the genetic underpinnings of alcohol-influenced aggression, a serious threat to public health. Further, this can identify the neural pathways of these genetic effects, which can inform psychological and pharmacological interventions that may prove fruitful in reducing the violent consequences of alcohol misuse. This award would support these goals and advance NIAAA's strategic plan to identify mechanisms underlying alcohol misuse and subsequent recovery.