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 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 病目前的治疗往往是不够的，没有药物已被证明是有效的。更好的 非常需要了解AN的病理生理学。避免高脂肪食物是一个核心 行为障碍有助于AN的发病率和死亡率，但对AN的基础知识知之甚少。 认知和神经机制。焦虑和对脂肪的恐惧被认为起着重要作用： AN通常高度焦虑，这种焦虑的主要焦点是食物或饮食相关。极端 在AN中，食物回避和食物周围的焦虑都有很好的记录，但这是一个机械的框架， 对这些现象及其相互关系的理解尚未得到严格的研究。拟议 一项研究测试了一种新的机制，这种机制可能是持续避免高热量，高脂肪 食物-过度概括的食物避免-并利用最近的进展，计算和 认知神经科学来阐明这一机制。通过使用新的范例，我们可以操作化 避免行为和量化的学习和威胁和安全信号的推广。我们的具体目标是 研究神经和认知机制支持AN中回避行为的泛化。我们将 使用功能性磁共振成像（fMRI）和计算建模来表征AN和 健康的比较参与者（HC），如何积极回避行为是广义的，当害怕 结果是电击（厌恶AN和HC）和高脂肪食物（厌恶AN）。我们的中心预测是 患有AN的个体在避免食物时比避免休克时会更广泛地概括， 这将与1）大脑回路的活动有关，包括纹状体，杏仁核和2）现实世界 避免高热量，高脂肪的食物。这项研究提出了一种新的机制来解释严重的 AN中的适应不良饮食行为，这已被证明是非常难以治疗的。 神经科学工具将允许在认知和神经两个方面更精确地说明机制。 水平，这是确定新的治疗目标，表征疾病的生物标志物， 脆弱性和轨迹，以及更广泛的转化研究。这项研究将为建立一个 大规模的R 01研究这些机制的发展和发展和测试 临床试验中的机制治疗。