Taste reward circuits and prediction error define eating disorder psychopathology

味觉奖励回路和预测误差定义了饮食失调精神病理学

• 批准号: 8678582
• 负责人: Guido KW Frank
• 金额: $ 38.72万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 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/8678582
• 关键词: Adolescent; Adolescent and Young Adult; Adult; Age; Anorexia Nervosa; Anterior; Area; Behavior; Binge Eating; Biological; Biology; Body mass index; Brain; Brain imaging; Bulimia; Categories; Classification; Clinical assessments; Corpus striatum structure; Data; Decision Making; Development; Diagnosis; Diagnostic; Diagnostic and Statistical Manual of Mental Disorders; Diffusion Magnetic Resonance Imaging; Dimensions; Disease; Dopamine; Eating Disorders; Emotional; Emotions; Funding Opportunities; Goals; Individual; Insula of Reil; Knowledge; Link; Magnetic Resonance; Measures; Mental disorders; Methods; Monitor; National Institute of Mental Health; Neurobiology; Neurosciences; Pathology; Patients; Pharmaceutical Preparations; Psychopathology; Punishment; Research; Research Domain Criteria; Rewards; Stimulus; Structure; Subgroup; Symptoms; System; Taste Perception; Testing; Underweight; Ventral Striatum; Weight; Youth; base; brain volume; cingulate cortex; dopaminergic neuron; effective therapy; excessive exercise; food restriction; gray matter; mortality; novel; public health relevance; purge; putamen; relating to nervous system; response; reward circuitry; white matter; young adult

Project Summary/Abstract The eating disorders (EDs) anorexia nervosa (AN) and bulimia nervosa (BN) are severe psychiatric disorders with high mortality. While AN is mainly characterized by severe underweight and BN individuals are at normal to high weight and regularly binge and purge, there are many overlapping symptoms across both disorders, such as food restriction, episodic binge eating, purging or excessive exercise. Little is known about the neurobiology of EDs and how specific ED behaviors are linked to particular biological mechanisms. The NIMH Funding opportunity "Advancing Eating Disorders Research through Dimensional Studies of Biology and Behavior" is in direct response to this lack of knowledge. In the present application, using the "Prediction Error" construct from the NIMH's Research Domain Criteria (RDoC) project, we examine how brain function and structure could be biological mechanisms underlying dimensions of ED relevant behaviors. This construct has been associated with specific brain reward circuit responses, which could be related to particular ED relevant behaviors. Aim 1. is to study how functional neural reward circuits underlie dimensions of ED pathology using the RDoC construct prediction error. This application will study all individuals ages 16- 29 years who present for ED treatment to capture the full range of ED pathology (conforming with RDoC requirements), to study the age range with the highest mortality rate for AN, and to identify potential developmental factors by studying adolescents and young adults while staying within a limited age range. The study will include detailed clinical assessments as well as functional magnetic resonance brain imaging (fMRI) for taste-reward prediction error response. ED relevant behaviors will be predicted by anteroventral striatum (caudate/putamen) as well as insula prediction error response. In addition, lower body mass index (BMI) in ED subjects will be associated with higher activation to reward value predicting conditioned stimuli in the anterior cingulate cortex, an area important for comparing options of behavior response to stimuli including reward. Aim 2. is to perform structural magnetic resonance brain imaging (sMRI) for gray and white matter volume, as well as diffusion tensor imaging for white matter integrity. We expect that more severe ED behaviors will predict lower caudate and insula volumes. In addition, gray matter volume in insula and ventral striatum will predict strength of functional brain reward activation from Aim 1. Aim 3. is to cluster ED individuals based on prediction error response instead of traditional DSM criteria, and compare ED relevant behaviors based on this new classification with age matched healthy adolescent and adult controls. Prediction error response will be superior to DSM in clustering of ED subjects by dimensions of sensitivity to salient stimuli and in contrast to controls. This will suggest that EDs are disorders of altered salience response.

项目概要/摘要 饮食失调（ED）、神经性厌食症（AN）和神经性贪食症（BN）是严重的精神疾病 死亡率很高。 AN的主要特点是体重严重不足，而BN个体则处于正常体重 体重过重以及经常暴饮暴食和排便，这两种疾病有许多重叠的症状， 例如限制食物、间歇性暴饮暴食、净化或过度运动。人们对此知之甚少 ED 的神经生物学以及特定的 ED 行为如何与特定的生物机制联系起来。国家精神卫生研究所 资助机会“通过生物学的维度研究推进饮食失调研究” “行为”是对这种知识缺乏的直接反应。在本申请中，使用“预测误差” 根据 NIMH 的研究领域标准 (RDoC) 项目构建，我们检查大脑功能和 结构可能是 ED 相关行为维度的生物机制。 这种结构与特定的大脑奖励回路反应有关，这可能与 与 ED 相关的特定行为。目标 1. 是研究功能性神经奖励回路如何构成维度的基础 使用 RDoC 构建预测误差的 ED 病理学。该应用程序将研究所有年龄 16- 29 年接受 ED 治疗以了解 ED 病理的全部范围（符合 RDoC 要求），研究 AN 死亡率最高的年龄范围，并确定潜在的 通过研究青少年和年轻人在有限的年龄范围内的发展因素。这 研究将包括详细的临床评估以及功能性磁共振脑成像（fMRI） 用于味觉奖励预测误差响应。前腹侧纹状体将预测 ED 相关行为 （尾状核/壳核）以及岛叶预测误差响应。此外，ED 患者的体重指数 (BMI) 较低 受试者将与较高的激活奖励值相关联，预测前部的条件刺激 扣带皮层，一个对于比较对刺激（包括奖励）的行为反应选项很重要的区域。目的 2. 对灰质和白质体积进行结构磁共振脑成像（sMRI） 作为白质完整性的扩散张量成像。我们预计更严重的 ED 行为将预示 较低的尾状核和岛叶体积。此外，岛叶和腹侧纹状体的灰质体积将预测 目标 1. 目标 3. 的功能性大脑奖励激活强度是根据预测对 ED 个体进行聚类 错误响应而不是传统的 DSM 标准，并基于此新标准比较 ED 相关行为 与年龄匹配的健康青少年和成人对照进行分类。预测误差响应将是 在对显着刺激的敏感度维度上对 ED 受试者进行聚类方面优于 DSM，并且与 控制。这表明 ED 是显着反应改变的疾病。