Food Avoidance in Anorexia Nervosa-A Test of Generalization Mechanisms

神经性厌食症的食物回避——泛化机制的测试

基本信息

批准号：
10549311
负责人：
JOANNA E STEINGLASS
金额：
$ 19.99万
依托单位：
NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10549311
关键词：
Affect Amygdaloid structure Anorexia Nervosa Anxiety Anxiety Disorders Automobile Driving Aversive Stimulus Behavior Behavior Therapy Behavioral Biological Markers Biological Response Modifier Therapy Brain Calories Clinical Trials Cognitive Computer Models Consumption Corpus striatum structure Data Development Diet Dietary intake Disease Eating Eating Behavior Eating Disorders Fatty acid glycerol esters Food Foundations Fright Functional Magnetic Resonance Imaging Functional disorder Hospitals Hyperactivity Impairment Individual Insula of Reil Intake Investigation Knowledge Laboratories Lead Learning Link Measures Mental disorders Morbidity - disease rate Neurosciences Outcome Participant Pathologic Patients Play Prefrontal Cortex Process Psychiatry Psychopathology Research Role Safety Severities Shock Signal Transduction Specific qualifier value Starvation Stimulus Testing Translational Research anxious avoidance behavior cognitive neuroscience computational neuroscience dietary restriction food avoidance food restriction improved mortality neural neuromechanism neuroregulation novel pharmacologic response tool

项目摘要

PROJECT SUMMARY Anorexia nervosa (AN) is a devastating disorder with a mortality rate among the highest of any psychiatric illness. Current treatments are often inadequate, and no pharmacologic agents have proven effective. A better understanding of the pathophysiology of AN is greatly needed. Avoidance of high-fat food is a central behavioral disturbance contributing to morbidity and mortality of AN, yet little is known about the underlying cognitive and neural mechanisms. Anxiety and fear of fat are thought to play important roles: individuals with AN are highly anxious in general, with the primary focus of this anxiety being food or eating related. Extreme food avoidance and anxiety surrounding food are well documented in AN, yet a mechanistic framework for understanding these phenomena and their relationship has not been rigorously studied. The proposed research tests a novel mechanism potentially underlying the persistent avoidance of high-calorie, high-fat food—excessive generalization of food avoidance—and leverages recent advances in computational and cognitive neuroscience to elucidate this mechanism. With the use of a novel paradigm, we can operationalize avoidance behavior and quantify learning and generalization of threat and safety signals. Our specific aim is to examine the neural and cognitive mechanisms supporting generalization of avoidance behavior in AN. We will use functional magnetic resonance imaging (fMRI) and computational modeling to characterize, in AN and healthy comparison participants (HC), how active avoidance behavior is generalized both when the feared outcome is electric shock (aversive to AN and HC) and high-fat food (aversive to AN). Our central prediction is that individuals with AN will generalize more broadly when avoiding food than when avoiding shock, and that this will be related to 1) activity in brain circuits involving the insula, striatum, and amygdala and 2) real-world avoidance of high-calorie, high-fat food. The study proposes a novel mechanism to account for the severely maladaptive eating behavior in AN, which has proven very difficult to treat. The application of computational neuroscience tools will allow for more precise specification of mechanisms at both the cognitive and neural levels, which is essential for identifying novel treatment targets, characterizing biomarkers of illness vulnerability and trajectory, and translational research more broadly. This study will create a foundation for a large-scale R01 to investigate these mechanisms developmentally and development and testing of mechanism-based treatments in clinical trials.

项目概要神经性厌食症 (AN) 是一种毁灭性的疾病，其死亡率是所有精神疾病中最高的目前的治疗方法往往不够充分，并且没有任何药物被证明是有效的。了解 AN 的病理生理学是非常必要的，避免高脂肪食物是一个核心。行为障碍导致 AN 的发病率和死亡率，但对其潜在的原因知之甚少对脂肪的焦虑和恐惧被认为起着重要作用：患有这种疾病的个体。一般来说，AN 非常焦虑，这种焦虑的主要焦点是与食物或极端饮食有关。 AN 中详细记录了回避食物和围绕食物的焦虑，但也有一个机制框架对这些现象及其关系的理解尚未经过严格的研究。研究测试了一种可能导致持续避免高热量、高脂肪的新机制食物——对避免食物的过度概括——并利用计算和技术方面的最新进展通过使用一种新颖的范式，我们可以利用认知神经科学来阐明这种机制。我们的具体目标是避免行为并量化威胁和安全信号的学习和概括。研究支持 AN 中回避行为泛化的神经和认知机制。使用功能磁共振成像 (fMRI) 和计算模型来表征 AN 和健康比较参与者（HC），当害怕的时候主动回避行为是如何普遍化的结果是电击（厌恶 AN 和 HC）和高脂肪食物（厌恶 AN）。患有 AN 的个体在避免食物时比避免电击时会更广泛地概括，并且这将与 1) 涉及岛叶、纹状体和杏仁核的大脑回路活动以及 2) 现实世界有关该研究提出了一种新的机制来解释严重的问题。 AN 中的适应不良饮食行为已被证明很难治疗。神经科学工具将允许更精确地规范认知和神经机制水平，这对于确定新的治疗目标、表征疾病的生物标志物至关重要这项研究将为更广泛的脆弱性和轨迹以及转化研究奠定基础。大规模 R01 来研究这些机制并开发和测试临床试验中基于机制的治疗。