Translational Research on Addiction to Palatable Food

美味食物成瘾的转化研究

• 批准号: 8666108
• 负责人: NICOLE M AVENA
• 金额: $ 14.9万
• 依托单位: ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-15 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8666108
• 关键词: Accounting; Address; Affect; Animal Model; Animals; Area; Award; Behavior; Behavioral; Binge Eating; Binge eating disorder; Biological; Brain; CREB1 gene; Canned Foods; Clinical; Clinical Research; Clinical Sciences; Complement; Control Groups; DSM-IV; Data; Dependence; Dependency; Detection; Development; Development Plans; Diagnosis; Diet; Disease; Doctor of Philosophy; Drug Addiction; Eating; Eating Disorders; Educational process of instructing; Elements; Epidemiology; Exhibits; Fatty acid glycerol esters; Feeding behaviors; Florida; Food; Food Preferences; Foundations; Funding; Future; Galanin; Gene Expression; General Population; Genes; Goals; Health; Hyperphagia; Hypothalamic structure; Incidence; Individual; Intake; Knowledge; Laboratory Research; Lead; Measures; Medicine; Mentors; Methods; Modeling; Molecular; Molecular Biology; Motivation; National Research Service Awards; Nature; Neurobiology; Neuropeptides; Neurosciences; Nucleus Accumbens; Nutrient; Obesity; Opiates; Overweight; Patients; Phase; Population; Pre-Clinical Model; Proteins; Psychiatry; Psychology; Psychometrics; Publications; Rattus; Reporting; Research; Research Personnel; Research Project Grants; Research Training; Resources; Rewards; Rodent Model; Role; Scientist; Series; Substance Addiction; Sucrose; System; Techniques; Testing; Training; Training and Education; Translational Research; United States National Institutes of Health; Universities; Validity and Reliability; Weight; Withdrawal; addiction; base; behavior measurement; career; career development; college; design; experience; feeding; food addiction; interest; lectures; meetings; neural circuit; neurochemistry; novel; overexpression; pre-clinical; pre-clinical research; pre-doctoral; preclinical study; prevent; professor; programs; research and development; research study; response; responsible research conduct; scientific organization; skills; statistics; sugar; theories; tool; translational approach; trend

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.

描述（由申请人提供）：随着肥胖率持续上升，需要新的、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独特的理论，即以暴饮暴食的形式过量食用可口食物可能类似于对食物的“成瘾”，伴随的行为和神经化学变化类似于毒瘾。这些数据和其他人的研究结果支持这样的理论，即过量食用可口食物可能会产生类似于对某些食物的依赖的极端动机，可能会加剧某些人暴饮暴食和随后的肥胖的冲动。由于必须测试暴饮暴食的动物模型在临床上是否可靠，因此在本提案中，我计划获得临床研究培训，以便我可以研究和完善心理测量方法，以评估临床肥胖或暴饮暴食患者的“食物成瘾”紊乱。此外，我计划在临床前研究中采取下一步行动，获取有关暴饮暴食对已知与成瘾有关的基因表达的影响的数据，并了解暴饮暴食如何影响不同类型的营养素（即，脂肪与糖）可以影响相关的大脑系统和随后的行为。我拥有一套综合技能，将在本提案中得到进一步发展，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。我有博士学位。普林斯顿大学心理学和神经科学博士学位以及洛克菲勒大学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学位期间开发的糖依赖动物模型。研究。这项研究已发表 33 篇出版物、许多演讲邀请和演讲以及多个奖项。此外，我还通过个人博士前和博士后 NIH NRSA 奖项以及小型私人基金会获得资金。认识到转化研究的重要性和有用性，我现在计划通过获得临床科学方面的额外培训来扩展我的研究技能。这将使我能够将我的暴饮暴食临床前研究与临床人群联系起来，这将有助于为“食物成瘾”理论提供进一步的有效性。该提案概述了一系列职业发展活动，这些活动将在关于过量食用可口食物以及随后可能出现的“食物成瘾”的转化研究的背景下进行。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，这是进行培训的理想场所。不仅精神病学系的附加医学部门有几位研究人员对研究“自然成瘾”感兴趣，而且整个佛罗里达大学的资源和个人都将成为这个研究项目和我的发展的资产作为一名独立科学家。我们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要素做出了独特的贡献。此外，我还确定了将为拟议实验贡献其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，以及参与科学组织、参加讲座和研讨会以及负责任的研究行为培训。研究培训将重点培养我作为临床研究员的技能，以便我能够对暴饮暴食和食物摄入异常进行转化研究。从长远来看，我希望拥有自己的教学和研究实验室，可以继续利用临床前和临床模型进行异常喂养行为的神经生物学研究。拟议的实验集中于开发一条探究的转化路线。目标 1 将采用临床研究实践和心理测量学，对肥胖和暴食症患者以及正常对照者修改和实施耶鲁大学食物成瘾量表，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”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 是一个临床前研究组件，它将使用已建立的动物模型来评估因过量摄入脂肪和糖而导致奖励相关大脑区域的行为和基因表达差异。目标 2 将在啮齿动物暴饮暴食模型中使用行为测量和分子生物学技术。这种转化研究方法将有助于更好地理解暴饮暴食的各个方面，并为未来模型的开发提供信息，以研究异常喂养行为的生物学基础，然后可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、程序化的转化研究项目。