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（由申请人提供）：饮食失调是异质性疾病，其特征是极端饮食限制，暴饮暴食和清除的异常行为。该课程通常涉及青少年的发作，而在超过一半的个体中，从主要限制到暴饮暴及/清除行为。限制与暴饮暴食表型基础的低体重饮食失调和机制的病理生理学几乎完全未知。一个关键的知识差距是这些疾病的发育轨迹的基本神经生物学（例如，从主要限制到暴饮暴食或清除）我们的初步数据表明，涉及改变调节性（体位稳定性）的食物动机途径的关键作用，包括改变的调节性（体位抑制）和积极的价值（奖励）系统在低水平饮食中的积极价（奖励）系统。 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.我们假设（i）成功限制低体重的青少年将具有较低的体内稳态和享乐食欲，fMRI的食物动机途径降低以及较高的后PYY，Oxytocin和CCK分泌；（ii）那些最容易受到暴饮暴食行为的人将具有更大的享乐胃，奖励区域的fMRI过度激活，较高的餐后生长素和较低的餐后瘦素和CCK分泌；（iii）那些发展或持续清除行为的人会表现出餐后饱满，饱满区域的fMRI过度激活以及餐后BDNF的更高。我们将使用fMRI范式，神经内分泌测定，行为范式和自我报告测量表征在RDOC框架内跨多个分析中的低体重饮食失调的青少年来测试该模型。然后，我们将关注这些人一年，以评估谁转向暴饮暴食/清除疾病并保持限制。我们将在低重量限制性饮食失调的成年人的试点数据的基础上，我们将使用我们团队开发和验证的新型食品动机范式。绘制标志性饮食失调行为（饮食限制，暴饮暴食，清除）和在监管和正价系统的总体领域的饮食动机途径之间的关系，在纵向较低的青少年群体中，低体重饮食失调的饮食障碍者将使我们能够理解机制，使我们能够理解失调的稳态和野性食品的动力。表征与饮食失调行为相关的神经回路，神经内分泌和行为特征（i）将洞悉这些高病态疾病的发病机理的机制，并且（ii）允许识别未来的治疗靶标的机制在饮食行为不断发展的时候以及干预可能改变疾病过程时的影响行为。