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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：
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
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/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

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.

摘要