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

• 批准号: 10373539
• 负责人: JOANNA E STEINGLASS
• 金额: $ 23.99万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373539
• 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; Pharmacology; Play; Prefrontal Cortex; Process; Psychiatry; Research; Role; Safety; Severities; Shock; Signal Transduction; Starvation; Stimulus; Testing; Translational Research; anxious; avoidance behavior; base; cognitive neuroscience; computational neuroscience; dietary restriction; food avoidance; food restriction; improved; mortality; neuromechanism; novel; relating to nervous system; response; tool

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.

项目摘要 厌食症（AN）是一种毁灭性疾病，在任何精神病学中最高的死亡率 疾病。当前的治疗通常不足，没有证明有效的药理学剂。更好 非常需要了解AN的病理生理学。避免高脂食物是中心 行为干扰有助于AN的发病率和死亡率，但对基础知之甚少 认知和神经机制。焦虑和对脂肪的恐惧被认为扮演着重要角色： AN通常非常焦虑，该动画的主要重点是食物或饮食相关。极端 避免食物和围绕食物的焦虑在AN中有充分的记录，但是一个机械框架 了解这些现象及其关系并非严格研究。提议 研究测试了一种潜在避免高热量的新型机制 食物 - 避免食物的渗透性 - 并利用计算和计算的最新进展 认知神经科学以阐明这种机制。通过使用新颖的范式，我们可以运营 避免行为，量化威胁和安全信号的学习和概括。我们的具体目的是 检查支持回避行为的概括的神经和认知机制。我们将 使用功能磁共振成像（fMRI）和计算建模在AN和 健康比较参与者（HC），当Feeed时，主动避免行为通常如何 结果是电击（厌恶AND和HC）和高脂食品（厌恶AN）。我们的核心预测是 在避免食物时，患有一个人会比避免冲击时更广泛地概括，然后 这将与1）涉及绝缘，纹状体和杏仁核和2）现实世界的脑回路的活性有关 避免高热量，高脂食品。该研究提出了一种新颖的机制，可以严重解释 AN的适应不良饮食行为，事实证明很难治疗。计算的应用 神经科学工具将允许在认知和神经元上更精确地规范机制 水平，这对于识别新型治疗目标至关重要，表征生物标志物的疾病 脆弱性和轨迹，更广泛地翻译研究。这项研究将为 大规模R01研究这些机制在开发以及开发和测试 基于机理的临床试验治疗。