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

基本信息

批准号：
10517967
负责人：
LAURA McGrath HOLSEN
金额：
$ 86.32万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
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：
2022-09-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10517967
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 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 Neuraxis 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 Suicide Sum Taste aversion Time Treatment outcome Vegetables Visual Vomiting Weight Woman Work Youth age group antagonist avoidant restrictive food intake disorder base 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

项目摘要

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.

抽象的回避/限制性食物摄入障碍 (ARFID) 影响 1-4% 的成年人，且与体重相关损失、营养缺乏、自杀和社会心理障碍的情况各不相同，且效果较差。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）；对饮食缺乏兴趣（ARFID-缺乏兴趣）和/或极端的食物选择性（ARFID- 对于这种严重的心理健康状况的病理生理学知之甚少，特别是对于患有慢性病的成年人，我们的研究将利用独特的方法。具有临床心理学专业知识的多学科团队的互补贡献，我们将通过神经内分泌学和神经科学来研究成人 ARFID 的病理生理学。建立一组年龄为 18-45 岁且具有 ARFID 的成年人 (n=150) 和健康对照者 (n=50) 进行匹配性别和年龄，以调查跨分析单元 RDoC 构建体如何影响 ARFID 表型。首先，我们带来了负价（急性威胁/恐惧）过度活跃（激素：皮质醇的反应）进餐；电路：杏仁核、前扣带皮层和眶额皮层在经过验证的过程中激活食物提示范式）将与 ARFID 的严重程度相关——对不良后果的恐惧。其次是唤醒/调节（稳态）功能障碍（激素：CKK、生长素释放肽）膳食；电路：在经过验证的食物提示范式期间下丘脑的激活）将与饮食的严重程度相关 ARFID-缺乏兴趣第三，我们过度关注认知系统（体感感知）。敏感性（激素：对膳食的催产素；电路：体感皮层的激活和在经过验证的食物提示范例期间补充运动皮层）将与 ARFID 的严重程度相关我们还预计每个 ARFID 表型在相应的方面都有更大的功能障碍。通过提供实证研究，RDoC 结构比对照具有创新性和独特性。一项未经充分研究的临床表现，并通过首次研究 ARFID 病理生理学总之，在整合内分泌信号的 RDoC 框架内概念化 ARFID。神经回路具有通过识别机制来推进 ARFID 精准医学的巨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）减轻ARFID整个生命周期的负担。