Translational Research on Addiction to Palatable Food

描述(由申请人提供)：随着肥胖率持续上升，需要新的和不同的研究方法来制定策略来阻止这一趋势。我一直在使用临床前模型来研究一种独特的理论，即以暴饮暴食的形式暴饮暴食，可能类似于对食物的“上瘾”，伴随着与药物成瘾类似的行为和神经化学变化。这些数据和其他人的发现支持了这样一种理论，即过量食用美味的食物可能会产生一种类似于对某些食物的依赖的极端动机，可能会加剧某些人的暴饮暴食的冲动，进而导致肥胖。由于必须测试暴饮暴食的动物模型是否在临床上可靠，在这项建议中，我计划接受临床研究培训，以便我可以研究和完善心理测量学方法，以评估肥胖或暴饮暴食障碍的临床患者的“食物成瘾”。此外，我计划在我的临床前研究中迈出下一步，通过获得过量饮食对已知在成瘾中起作用的基因表达的影响的数据，并了解过度饮食对不同类型的营养物质(即脂肪和糖)如何影响相关的大脑系统和后续行为。我有一套综合技能，将在这项建议中得到进一步发展，这将使我能够完成这些研究，并促进我作为一名独立研究科学家的发展。我在普林斯顿大学获得心理学和神经科学博士学位，在洛克菲勒大学获得分子生物学博士后经验。我现在是佛罗里达大学医学院精神病学系的助理研究教授。到目前为止，我的研究重点是利用我在行为神经科学和分子生物学方面的技能来研究“食物成瘾”，部分是通过使用我在博士研究中开发的糖依赖动物模型。这项研究已经发表了33篇文章，收到了许多演讲邀请和演讲，并获得了几个奖项。此外，我有通过个人NIH NRSA博士前和博士后奖项以及小型私人基金会获得资金的记录。认识到翻译研究的重要性和用处，我现在计划通过获得更多的临床科学培训来扩大我的研究技能。这将使我能够将我对暴饮暴食的临床前研究与临床人群联系起来，这将有助于进一步验证“食物成瘾”理论。这份提案概述了一系列职业发展活动，这些活动将在关于吃得过多的可口食物和随之而来的可能发展成“食物成瘾”的翻译研究的背景下进行。研究和职业发展活动将在佛罗里达大学医学院精神病学系进行，这是进行这种培训的理想地点。精神病学系的附加医学分部不仅有几名研究人员对研究“自然成瘾”感兴趣，而且整个佛罗里达大学的资源和个人也将成为这项研究项目和我作为一名独立科学家发展的一笔财富。已经组建了一个导师团队来指导我完成这个发展阶段，每个人都对拟议的培训和研究内容做出了独特的贡献。此外，我已经确定了将为拟议的实验贡献他们的专业知识和知识的合作者。职业发展计划包括临床研究、流行病学和统计学方面的高级课程，以及参加科学组织、参加讲座和研讨会，以及负责任地进行研究的培训。研究培训将重点发展我作为临床研究人员的技能，这样我就可以对暴饮暴食和异常食物摄入进行翻译研究。从长远来看，我希望有自己的教学和研究实验室，在那里我可以继续使用临床前和临床模型对异常摄食行为的神经生物学进行研究。拟议中的实验的中心是开发一条转译的探究路线。目的1)利用临床研究实践和心理测量学，在肥胖和暴饮暴食障碍患者和正常对照组中修改和实施耶鲁食物成瘾量表，以1)使用该量表确定这些临床人群中的患者是否表现出“食物成瘾”的迹象，以及2)使用新开发的子量表将食物偏好与成瘾行为联系起来。此外，为了告知和扩展这些发现，Aim 2是一个临床前研究部分，将使用已建立的动物模型评估与奖励相关的大脑区域中因过量摄入脂肪和糖而导致的行为和基因表达的差异。目的2将行为测量和分子生物学技术应用于过量进食的啮齿动物模型。这种翻译的研究方法将使人们能够更好地理解暴饮暴食的各个方面，并为未来模型的发展提供信息，以调查异常摄食行为的生物学基础，然后将其应用于临床人群的研究。培训结束后，我将能够开始作为一名独立调查员的职业生涯，并准备开发一个全面的、有计划的翻译研究项目。

DESCRIPTION (provided by applicant): With obesity rates continuing to rise, new and different research approaches are needed to develop strategies to impede this trend. I have been using preclinical models to study the unique theory that overeating of palatable foods, in the form of binge eating, can resemble an "addiction" to food, with concomitant behaviors and neurochemical changes that are like those seen with drug addiction. These data and the findings of others support the theory that overeating of palatable food might produce an extreme motivation that resembles a dependency on certain foods, possibly fueling the urge to overeat and subsequent obesity in some individuals. As it is imperative to test whether animal models of overeating are clinically reliable, in this proposal I plan to obtain clinical research training so that I can study and refine psychometric methods to assess "food addiction" in clinical patients who are obese or have binge eating disorder. Further, I plan to take the next step in my preclinical research by obtaining data on the effect that overeating can have on the expression of genes that are known to have roles in addiction, and to understand how overeating on different types of nutrients (i.e., fat vs. sugar) can affect related brain systems and subsequent behavior. I have an aggregate skill set that will be further developed in this proposal, which will enable me to complete these studies and facilitate my development as an independent research scientist. I have a Ph.D. in Psychology and Neuroscience from Princeton University and postdoctoral experience in molecular biology from The Rockefeller University. I am now Assistant Research Professor at University of Florida, College of Medicine, Department of Psychiatry. My research studies up to this point have focused on using my skills in behavioral neuroscience and molecular biology to study of "food addiction," in part, through the use of an animal model of sugar dependence that I developed in my Ph.D. research. This research has resulted in 33 publications, many speaking invitations and presentations, and several awards. Further, I have a track record of obtaining funding through individual predoctoral and postdoctoral NIH NRSA awards, and small private foundations. Recognizing the importance and usefulness of translational research, I now plan to expand my research skills by obtaining additional training in clinical science. This will allow me to relate my preclinical studies of overeating to clinical populations, and this will help to provide further validity to the theory of "food addiction." This proposal outlines a series of career development activities that will be conducted within the context of translational research on overeating palatable foods and the possible ensuing development of "food addiction." The research and career development activities will occur at the University of Florida, College of Medicine, Department of Psychiatry, which is an ideal place for this training to take place. Not only are there several researchers in the Addition Medicine division of the Department of Psychiatry who are interested in studying "natural addictions," but there are also resources and individuals throughout the University of Florida that will be an asset to this research project and my development as an independent scientist. A team of mentors has been assembled to guide me through this development phase, each with a unique contribution to the proposed training and research elements. In addition, I have identified collaborators that will contribute their expertise and knowledge to the proposed experiments. Career development plans include advanced coursework in clinical research, epidemiology and statistics, as well as participation in scientific organizations, attendance to lectures and seminars, and training in the responsible conduct of research. The research training will focus on developing my skills as a clinical researcher so I can conduct translational research on overeating and abnormal food intake. In the long term, I hope to have my own teaching and research laboratory in which I can continue to conduct research on the neurobiology of aberrant feeding behavior using both preclinical and clinical models. The proposed experiments are centered on developing a translational line of inquiry. Aim 1 will employ clinical research practices and psychometrics to modify and implement the Yale Food Addiction Scale in obese and binge eating disorder patients and normal controls to 1) determine if patients in these clinical populations show signs of "food addiction" using this scale, and 2) relate food preference to the addiction-like behaviors using newly-developed subscales. Further, to inform and expand on these findings, Aim 2 is a preclinical research component that will assess differences in behaviors and gene expression in reward-related brain areas that result from overeating fat vs. sugar using established animal models. Aim 2 will use behavioral measures and molecular biological techniques in rodent models of overeating. This translational approach to research will permit a better understanding of various aspects of overeating and inform the development of future models to investigate the biological basis of aberrant feeding behavior, which may then be applied to studies in clinical populations. At the end of this training, I will be able to launch a career as an independent investigator and be poised to develop a comprehensive, programmatic translational research program.