Multimodal Neuroimaging of Alcohol Cues, Cortisol Response and Compulsive Motivation

项目总结 申请者的长期职业目标是发展一项独立的研究项目 酒精使用障碍(AUDS)发生的神经生物学机制，特别是 与酗酒有关。2014年全国毒品使用与健康调查结果显示，26%的 在过去的一个月里，美国成年人参与了狂欢饮酒(Samsa 2014)。为什么有些人会“成熟起来” 在其他人坚持的时候，这种行为可能是由于一个人对酗酒的生理反应。没有以前的记录 一项研究评估了皮质醇和神经网络对酒精暗示的反应中断是否会导致 在还没有AUD的狂饮人群中出现的强迫性酒精消费。超过了 在申请者的职业生涯中，她希望有助于我们对基因组、神经内分泌、 以及AUDS发展的神经机制。 到目前为止，她已经接受了出色的神经化学和神经解剖学方面的培训 参与急性酒精对大脑和大脑的影响的底物(从遗传学到功能网络) 严重AUDS的慢性、复发性病程。在临床和行为神经科学的坚实基础上，她 现在的目标是在耶鲁大学高效和支持性的基础设施内获得进一步的培训(1) 先进的多模式神经成像技术，(2)危险饮酒发病前的临床过程 以及(3)多层次、混合影响的纵向分析，以启动独立职业生涯 酒精中毒跨学科、转化性神经科学研究领域的研究人员。如果没有这个 K99/R00独立之路奖，申请者将没有受保护的时间、培训或 资源，以启动这一新的研究方向。这项严格的K99培训计划将帮助申请者 获得制定长期研究计划所需的新技能，该计划包含多个 AUDS发展研究中的跨学科方法。该培训计划将通过以下方式实现：1) 结构化的指导计划2)有指导的研究经验，3)正式的课程和 研讨会/讲习班，以及4)出席国家和国际会议。 在R00阶段，为了通过独立研究项目进一步培训申请者， 应聘者将招募21-45岁(N=90，性别平等)的喝啤酒、不吸烟的男性和女性 适度饮酒者或酗酒/重度饮酒者进行单一的神经成像和神经内分泌评估，以 确定他们在未来一个月的前瞻性跟踪中的真实饮酒行为是否可以根据 根据皮质醇和神经网络对酒精暗示的反应。最后，遗传变异对人类健康的影响 调节皮质醇活性的FK506结合蛋白5基因在皮质醇和神经网络上的作用 本课程将探讨对酒精暗示的反应。这项研究将成为建立理解 导致人类AUDS风险的神经生物学变化。

PROJECT SUMMARY The long-term career goal of the applicant is to develop an independent program of research on the neurobiological mechanisms underlying the development of Alcohol Use Disorders (AUDs), specifically those related to binge drinking. Results from the 2014 National Survey on Drug Use and Health show that 26% of adults in the US engaged in binge drinking in the past month (SAMSA 2014). Why some people “mature out” of this behavior while others persist may be due to one’s physiological response to binge drinking. No previous study has assessed whether disrupted cortisol and neural network responses to alcohol cues may drive the compulsive alcohol consumption seen in binge drinking individuals who do not yet have an AUD. Over the course of the applicant’s career, she hopes to contribute to our understanding of the genomic, neuroendocrine, and neural mechanisms that underlie the development of AUDs. So far, she has received excellent training regarding the neurochemical and neuroanatomical substrates (from genetics to functional networks) involved in the effects of acute alcohol on the brain and in the chronic, relapsing course of severe AUDs. On this solid foundation of clinical and behavioral neuroscience, she now aims to obtain further training within the highly productive and supportive infrastructure at Yale in (1) advanced multimodal neuroimaging techniques, (2) the clinical course of hazardous drinking prior to the onset of AUDs, and (3) multilevel, mixed effects longitudinal analyses to launch a career as an independent researcher in the field of interdisciplinary, translational neuroscience research on alcoholism. Without this K99/R00 Pathway to Independence Award, the applicant will not have the protected time, training, or the resources to initiate this new direction of research. This rigorous K99 training program will help the applicant obtain a new skill set required to develop a long-term program of research which incorporates multiple interdisciplinary methods in the study of the development of AUDs. This training plan will be achieved via: 1) structured mentoring programs 2) supervised research experience, 3) formal coursework and seminars/workshops, and 4) attendance at national and international conference meetings. To further the applicant’s training with an independent research project, during the R00 phase, the applicant will recruit beer drinking, non-smoking men and women ages 21-45 (N=90, equal gender) who are either moderate drinkers or binge/heavy drinkers for a single neuroimaging and neuroendocrine assessment to determine if their real world drinking behavior in a prospective one month follow up can be predicted based upon the cortisol and neural network responses to alcohol cues. Finally, the influence of genetic variation in the FK506-binding protein 5 (FKBP5) gene, which regulates cortisol activity, on the cortisol and neural network responses to alcohol cues will be explored. This study will be the basis to build a career in understanding the neurobiological changes that drive risk of AUDs in humans.