Neurobiological Underpinnings of Avoidant/Restrictive Food Intake Disorder in Adults

成人回避/限制性食物摄入障碍的神经生物学基础

• 批准号: 10687206
• 负责人: LAURA McGrath HOLSEN
• 金额: $ 84.6万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10687206
• 关键词: Acute; Adolescent; Adult; Affect; Age; Agonist; Allergic Reaction; Amygdaloid structure; Anterior; Appetite Stimulants; Area Under Curve; Arousal; Behavioral; Body Weight decreased; Body mass index; Brain; Central Nervous System; Child; Choking; Cholecystokinin; Chronic; Clinical; Clinical Psychology; Cues; Data; Dependence; Dimensions; Disease; Distress; Eating; Eating Disorders; Endocrine; Evidence based treatment; Exhibits; Feeling; Food; Fright; Functional disorder; Homeostasis; Hormonal; Hormones; Hydrocortisone; Hyperactivity; Hypothalamic structure; Impairment; Individual; Intake; Interest Group; Intervention; Investigation; Longevity; Magnetic Resonance Imaging; Malnutrition; Mental Health; Modeling; Motor Cortex; National Institute of Mental Health; Negative Valence; Neurobiology; Neuroendocrinology; Neurosciences; Oxytocin; Perception; Persons; Pharmaceutical Preparations; Phenotype; Public Health; Reporting; Research; Research Domain Criteria; Risk; Sensory Disorders; Severities; Signal Transduction; Somatosensory Cortex; Standardization; Stimulus; Stress; Taste aversion; Time; Treatment outcome; Vegetables; Visual; Vomiting; Weight; Woman; Work; Youth; age group; antagonist; avoidant restrictive food intake disorder; behavioral phenotyping; cingulate cortex; cognitive system; cohort; data archive; dietary supplements; experience; feeding; food restriction; gastrointestinal; ghrelin; gray matter; innovation; interest; medical complication; men; multidisciplinary; neural circuit; neuroregulation; novel; precision medicine; psychiatric comorbidity; psychosocial; response; secondary analysis; severe mental illness; sex; somatosensory; suicidal

ABSTRACT Avoidant/restrictive food intake disorder (ARFID) affects 1-4% of adults and is associated with weight loss, nutritional deficiencies, suicidality, and psychosocial impairment. ARFID is heterogeneous, with poor intake characterized by extreme fear of choking, vomiting, or allergic reaction (ARFID-fear of aversive consequences); lack of interest in eating (ARFID-lack of interest); and/or extreme food selectivity (ARFID- sensory sensitivity). Very little is known about the pathophysiology of this serious mental health condition, particularly among adults whose illness has followed a chronic course. Our study will leverage unique and complementary contributions of a multidisciplinary team with expertise in clinical psychology, neuroendocrinology, and neuroscience to investigate the pathophysiology of ARFID in adults. We will establish a cohort of adults age 18-45 years with ARFID (n=150) and healthy controls (n=50) matched for sex and age to investigate how, across units of analysis, RDoC constructs contribute to ARFID phenotypes. First, we hypothesize that Negative Valence (acute threat/fear) hyperactivity (hormones: cortisol in response to a meal; circuitry: amygdala, anterior cingulate cortex, and orbitofrontal cortex activation during a validated food-cue paradigm) will correlate with severity of ARFID-fear of aversive consequences. Second, we hypothesize that Arousal/Regulatory (homeostasis) dysfunction (hormones: CKK, ghrelin in response to a meal; circuitry: hypothalamus activation during a validated food-cue paradigm) will correlate with severity of ARFID-lack of interest. Third, we hypothesize that Cognitive Systems (somatosensory perception) over- sensitivity (hormones: oxytocin in response to a meal; circuitry: activation in the somatosensory cortex and supplemental motor cortex during a validated food-cue paradigm) will correlate with severity of ARFID- sensory sensitivity. We also expect each ARFID phenotype to have greater dysfunction in the corresponding RDoC construct than controls. This study will be innovative and unique by providing an empirical investigation of an understudied clinical presentation and by investigating—for the first time—ARFID pathophysiology in adults. In sum, conceptualizing ARFID within an RDoC framework that integrates both endocrine signaling and neural circuitry has strong potential to advance precision medicine in ARFID by identifying mechanistic targets that could be intervened upon (e.g., through neuromodulation and/or hormone agonists/antagonists) to reduce the burden of ARFID across the lifespan.

摘要 回避性/限制性食物摄入障碍(ARFID)影响1-4%的成年人，并与体重有关 丧失、营养不足、自杀和心理社会损害。ARFID是异质的，贫乏 以极度害怕窒息、呕吐或过敏反应为特征的摄入(ARFID-害怕厌恶 后果)；对进食缺乏兴趣(ARFID-缺乏兴趣)；和/或极端的食物选择性(ARFID- 感官敏感性)。人们对这种严重心理健康状况的病理生理学知之甚少， 尤其是在疾病经过慢性病程的成年人中。我们的研究将利用独特的和 具有临床心理学专业知识的多学科团队的互补贡献， 神经内分泌学和神经科学研究成人ARFID的病理生理学。我们会 建立年龄在18-45岁、ARFID(n=150)和健康对照(n=50)匹配的成人队列 性别和年龄，以研究在不同的分析单位中，RDoC结构如何影响ARFID表型。 首先，我们假设负价(严重威胁/恐惧)多动(激素：皮质醇的反应 环路：杏仁核、前扣带回皮质和眼眶额叶皮质在有效的 食物线索范式)将与ARFID的严重程度相关--对令人厌恶的后果的恐惧。第二，我们 假设唤醒/调节(内稳态)功能障碍(激素：CKK，Ghrelin对 膳食；回路：在有效的食物线索范例中激活下丘脑)将与 ARFID-缺乏兴趣。第三，我们假设认知系统(体感知觉)过度- 敏感性(荷尔蒙：对进餐反应的催产素；回路：躯体感觉皮质和 在经过验证的食物线索范例中补充运动皮质)将与ARFID的严重程度相关。 感官敏感度。我们还预计每种ARFID表型在相应的 RDoC构造比控件。这项研究将具有创新性和独特性，通过提供一个实证调查 通过首次对ARFID的病理生理学进行调查 成年人。总之，在RDoC框架内将ARFID概念化，该框架集成了两种内分泌信号 而神经回路通过识别机制，在ARFID中具有推动精确医学的强大潜力 可以干预的目标(例如，通过神经调节和/或激素激动剂/拮抗剂) 以减轻ARFID在整个生命周期内的负担。