Genetic and Neural Factors in Alcohol-Influenced Aggression

项目总结/摘要 本K 01指导研究科学家发展奖提案旨在为大卫切斯特博士提供 必要的培训和研究经验，以推进他的职业目标，成为一个独立的 酒精调查员他寻求这一职业目标是为了更好地理解和干预生物学。 碱基（即，遗传风险因素，神经机制）的酒精影响的侵略。其中的活动 这项提案将建立在切斯特博士在攻击性心理和神经基础方面的现有技能基础上。 行为 培训计划：切斯特博士寻求先进的遗传技术和酒精滥用表型的培训， 这将通过一个结构化的培训计划来实现，该计划包括与导师定期举行会议， 外部实验室轮换，课程和统计遗传学研讨会，指导阅读，和两个 实验室轮换切斯特博士的培训计划利用了杰出的研究和教育 弗吉尼亚联邦大学（VCU）的环境与知名专家团队作为导师。他 主要导师是Danielle Dick博士（酒精滥用和相关遗传风险因素方面的专家）。 外化行为）。切斯特博士也将共同指导博士大卫高盛（专家对 酒精滥用和相关外化行为的遗传和神经基础），法齐尔·阿利耶夫博士（专家 统计遗传学），多米尼克鹦鹉博士（酒精影响的侵略专家），和F。Gerard Moeller（酒精滥用和相关外化行为的神经基础专家）。 研究计划：本K 01提案的科学目标是检查易患 某些人在滥用酒精的情况下表现得咄咄逼人。此外，我们计划调查 这些神经机制将这些遗传风险因素与酒精影响的实际攻击行为联系起来。遗传 酒精影响的攻击性的风险因素将通过分析来自[五个NIH资助的 公开可用的基因组数据集]和从VCU的NIAAA资助的Spit 4Science收集的新样本 该项目调查了大学生中纵向的酒精滥用轨迹。探讨 神经机制，Spit 4Science参与者的子样本将被招募进行一项研究， 联合收割机结合安慰剂控制的酒精管理，实验室攻击措施，和功能性大脑 成像（fMRI）。这项拟议的研究是第一次系统地调查遗传基础， 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，可以告知心理和药理干预， 在减少酒精滥用的暴力后果方面卓有成效。该奖项将支持这些目标， 推进NIAAA的战略计划，以确定潜在的酒精滥用和随后的恢复机制。

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.