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Homeostatic and Hedonic Food Motivation Underlying Eating Disorder Trajectories

饮食失调轨迹背后的稳态和享乐食物动机

基本信息

批准号：
9036458
负责人：
Kamryn T Eddy
金额：
$ 66.32万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9036458
关键词：
Address Adolescence Adolescent Adult Amygdaloid structure Appetite Disorder Appetite Stimulants Behavior Behavioral Behavioral Paradigm Binge Eating Biological Assay Body Weight Changes Brain region Brain-Derived Neurotrophic Factor Characteristics Cholecystokinin Data Desire for food Development Disease Eating Eating Behavior Eating Disorders Endocrine Exhibits Expectancy Fasting Food Frequencies Functional Magnetic Resonance Imaging Functional disorder Future Health Hippocampus (Brain)Hormones Hunger Hypothalamic structure Image Individual Insula of Reil Intervention Knowledge Lead Leptin Maps Measurement Measures Modeling Motivation Neurobiology Neurosecretory Systems Outcome Outcome Measure Oxytocin Pathogenesis Pathway interactions Patient Self-Report Pattern Pediatrics Phenotype Positive Valence Psychiatry Psychopathology Reporting Research Domain Criteria Rewards Satiation Symptoms System Testing Time Weight Weight Gain Weight maintenance regimen Woman Work binge type behavior cohort dietary restriction food restriction ghrelin girls healthy weight hedonic innovation insight longitudinal course mortality neural circuit neuroimaging novel purge purging behavior restoration skills therapeutic target

项目摘要

DESCRIPTION (provided by applicant): Eating disorders are heterogeneous illnesses characterized by aberrant behaviors of extreme dietary restriction, binge eating, and purging. The course often involves adolescent onset, and in more than half of individuals, transition from predominantly restrictive to binge/purge behaviors. The pathophysiology of low- weight eating disorders and mechanisms that underlie restricting vs. binge/purge phenotypes are almost entirely unknown. A critical knowledge gap is the neurobiology underlying the developmental trajectory of these illnesses (e.g. transition from primary restriction to binge eating or purging) Our preliminary data argue for a key role of food motivation pathways involving altered Regulatory (homeostatic) and Positive Valence (reward) systems in low-weight eating disorders. Consistent with the Research Domain Criteria (RDoC) initiative, the current study leverages the complementary skills of Multiple-PIs, Dr. Misra from Pediatrics, Dr. Lawson from the Neuroendocrine Unit and Dr. Eddy from Psychiatry to address this knowledge gap through examination of homeostatic and hedonic food motivation pathways that we hypothesize underlie the longitudinal course of these key eating disorder behaviors. We hypothesize that (i) adolescents who successfully restrict to maintain low weight will have lower homeostatic and hedonic appetite, fMRI hypoactivation of food motivation pathways, and higher postprandial PYY, oxytocin and CCK secretion; (ii) those most vulnerable to binge eating behavior will have greater hedonic appetite, fMRI hyperactivation of reward regions, higher postprandial ghrelin and lower postprandial leptin and CCK secretion; and (iii) those who develop or persist in purging behavior will exhibit increased postprandial fullness, fMRI hyperactivation of satiety regions, and higher postprandial BDNF. We will test this model by characterizing adolescents with low-weight eating disorders across multiple units of analysis within an RDoC framework using an fMRI paradigm, neuroendocrine assays, behavioral paradigms, and self-report measures. We will then follow these individuals for a year to assess who switches to a binge/purge illness and who maintains restriction. Building on our pilot data in adults with low-weight restrictive eating disorders, we will use a novel food motivation paradigm developed and validated by our team. Mapping the relationship between hallmark eating disorder behaviors (dietary restriction, binge eating, purging) and food motivation pathways across the overarching domains of the Regulatory and Positive Valence Systems in a longitudinal cohort of adolescents with low-weight eating disorders will enable us to understand mechanisms whereby dysregulated homeostatic and hedonic food motivation lead to development of these behaviors. Characterizing the neural circuitry, neuroendocrine, and behavioral features associated with eating disorder behaviors will (i) provide insight into mechanisms underlying the pathogenesis of these high-mortality illnesses and (ii) allow for identification of future therapeutic targets that impact behavior at a time when eating behaviors are evolving and when intervention may change disease course.

描述(申请人提供)：进食障碍是一种异质性疾病，以极端限制饮食、暴饮暴食和排泄等异常行为为特征。这一过程通常涉及青春期发作，在超过一半的人中，从主要的限制性行为过渡到狂欢/清洗行为。低体重进食障碍的病理生理学机制和限制与暴饮暴食/排泄表型之间的关系几乎完全未知。一个关键的知识缺口是这些疾病发展轨迹(例如，从最初的限制到暴食或清除的转变)的神经生物学。我们的初步数据表明，食物动机途径在低体重饮食障碍中发挥了关键作用，涉及改变的调节(稳态)和正价(奖励)系统。与研究领域标准(RDoC)倡议一致，目前的研究利用多PI、儿科的Misra博士、神经内分泌科的Lawson博士和精神病学的Eddy博士的互补技能，通过检查动态平衡和享乐性食物动机路径来解决这一知识差距，我们假设这些关键饮食失调行为的纵向过程是基于这些路径的。我们假设：(I)成功限制保持低体重的青少年将具有更低的稳态和享乐食欲，功能磁共振成像对食物动机通路的低激活，以及更高的餐后PYY、催产素和CCK分泌；(Ii)那些最容易受到暴饮暴食行为影响的青少年将具有更大的享乐食欲，奖励区域的功能磁共振成像过度激活，更高的餐后胃促生长素和CCK分泌；以及(Iii)发展或坚持通便行为的青少年将表现出更高的餐后饱腹感，饱腹区的功能磁共振成像过度激活，以及更高的餐后BDNF。我们将通过使用功能磁共振成像范式、神经内分泌分析、行为范式和自我报告测量，在RDoC框架内的多个分析单元中对患有低体重饮食障碍的青少年进行特征描述，以测试这一模型。然后，我们将对这些人进行为期一年的跟踪，以评估谁会转向暴饮暴食/大扫除疾病，谁会保持限制。基于我们在患有低体重限制性饮食障碍的成年人中的试点数据，我们将使用由我们的团队开发和验证的一种新的食物动机范式。在一组患有低体重饮食障碍的青少年纵向队列中，绘制标志性饮食障碍行为(饮食限制、暴饮暴食、通便)与食物动机途径之间的关系，将使我们能够理解调节失调的稳态和享乐食物动机导致这些行为发展的机制。表征与进食障碍行为相关的神经回路、神经内分泌和行为特征将(I)提供对这些高死亡率疾病发病机制的洞察和(Ii)允许确定未来的治疗靶点在饮食行为正在演变以及干预可能改变疾病进程的时候，影响行为。