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 避免/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、营养缺乏、自杀和心理社会损害。ARFID是异质性的， 以极度害怕窒息、呕吐或过敏反应为特征的摄入（ARFID-害怕厌恶性 缺乏兴趣（ARFID-缺乏兴趣）;和/或极端的食物选择性（ARFID- 感官灵敏度）。对这种严重的精神健康状况的病理生理学知之甚少， 特别是在患有慢性疾病的成年人中。我们的研究将利用独特的， 具有临床心理学专业知识的多学科团队的补充贡献， 神经内分泌学和神经科学研究成人ARFID的病理生理学。我们将 建立一个年龄为18-45岁的ARFID成年人（n=150）和健康对照组（n=50）的队列， 性别和年龄，以研究RDoC构建体如何在分析单元中促成ARFID表型。 首先，我们假设负价（急性威胁/恐惧）多动（激素：皮质醇反应） 电路：杏仁核，前扣带皮层和眶额皮层激活在一个有效的 食物提示范式）将与ARFID的严重程度-对厌恶后果的恐惧相关。二是 假设唤醒/调节（稳态）功能障碍（激素：CKK，ghrelin， 膳食;回路：在经验证的食物线索范例期间下丘脑激活）将与 ARFID-缺乏兴趣。第三，我们假设认知系统（体感感知）过度- 敏感性（激素：对进餐的催产素反应;回路：躯体感觉皮层的激活， 在验证的食物提示范例期间补充运动皮层）将与ARFID的严重程度相关- 感觉灵敏度我们还预计，每种ARFID表型在相应的细胞中有更大的功能障碍。 RDoC构建体比对照。本研究将通过提供一个实证调查， 研究不足的临床表现，并通过首次阐明ARFID的病理生理学， 成年人了总之，在RDoC框架内概念化ARFID， 神经回路具有很强的潜力，通过识别机制， 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） 减少ARFID在生命周期中的负担。