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Neurobiological and Behavioral Risk Mechanisms of Youth Avoidant/Restrictive Eating Trajectories

青少年回避/限制性饮食轨迹的神经生物学和行为风险机制

基本信息

批准号：
9433685
负责人：
Elizabeth Austen Lawson
金额：
$ 56.5万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-15 至 2021-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9433685
关键词：
Acute Adolescence Adolescent Age Amygdaloid structure Anxiety Anxiety Disorders Appetite Stimulants Arousal Behavior Behavioral Biometry Body mass index Brain-Derived Neurotrophic Factor Categories Child Child Psychiatry Childhood Choking Cholecystokinin Chronic Clinical Clinical Psychology Cognitive Comorbidity DSM-V Desire for food Detection Development Dimensions Discrimination Disease Eating Eating Disorders Endocrinology Exhibits Feeding behaviors Food Food Aversion Fright Functional Magnetic Resonance Imaging Functional disorder Galvanic Skin Response Growth Heart Rate Homeostasis Hormones Hunger Hydrocortisone Hypothalamic structure Image Impairment Individual Insula of Reil Intake International Intervention Investigation Literature Malnutrition Mental disorders Mind Modeling National Institute of Mental Health Negative Valence Neurobiology Neurodevelopmental Disorder Neurosecretory Systems Odors Outcome Oxytocin Pathogenesis Patient Self-Report Pediatrics Perception Phenotype Phobias Physiological Physiology Prevention Psychopathology Public Health Recovery Research Domain Criteria Resistance Risk Sensory Severities Site Sum Taste Perception Time Vomiting Youth aged appetite loss boys brain behavior cognitive system cohort disease classification feeding follow-up ghrelin girls innovation insight interest multidisciplinary neuroimaging nutrition outcome prediction prospective psychiatric symptom psychosocial public health relevance relating to nervous system response self reported behavior sex therapeutic target three-dimensional modeling trait

项目摘要

DESCRIPTION (provided by applicant): Avoidant and restrictive eating is common across youth mental health disorders, and is prospectively associated with poor growth, nutritional deficiencies, psychiatric symptoms, and psychosocial impairment. The newly introduced DSM-5 Avoidant/Restrictive Food Intake Disorder includes some (but not all) avoidant and restrictive eating presentations. Initial evidence suggests that avoidant and restrictive eating is highly heterogeneous, with poor intake characterized by choking or vomiting phobias; loss of interest in feeding; and/or extreme food selectivity. Moreover, very little is known about its pathophysiology or long- term outcomes. Our study will leverage unique and complementary contributions of an international team with expertise in clinical psychology, child psychiatry, pediatrics, endocrinology, biostatistics and functional neuroimaging to investigate risk mechanisms and longitudinal outcomes of avoidant and restrictive eating. We will establish a clinical cohort of children aged 8-18 years (n=100) and healthy controls (n=50) matched for sex, age, and Tanner stage to investigate how, across units of analysis, RDoC constructs contribute to avoidant and restrictive eating. First, we hypothesize that Negative Valence (acute threat/fear) over-activity (circuits: amygdala activation during a validated fear paradigm; hormones: cortisol and oxytocin; physiology: heart rate and skin conductance; self report: fear and trait anxiety) will correlate with phobic features. Second, we hypothesize that Arousal/Regulatory (homeostasis) dysfunction (circuits: hypothalamus and insula hypoactivation during a validated food paradigm; hormones: PYY, CKK, BDNF; self report: hunger and fullness) will correlate with low-appetite features. Third, we will explore Cognitive Systems (perception) over-sensitivity (circuits: hyperactivation in primary taste cortex during a taste paradigm; hormones: PYY; self report: sensory profile; behavior: taste and odor threshold, discrimination, and detection; physiology: taste perception) and its correlation with sensory features. We expect that the clinical cohort will have greater dysfunction across these 3 constructs than controls. We will then use latent class factor models to determine whether avoidant/restrictive eating comprises multiple distinct phenotypes (as prior literature assumes) or a single phenotype with 3 overlapping dimensions (as we hypothesize). We will follow our clinical cohort for 2 years to evaluate a) the persistence of avoidant/restrictive eating, growth, and psychopathology outcomes; and b) if dysfunction in all 3 RDoC constructs predicts outcomes. This study will be innovative and unique in 3 ways: 1) by providing an empirical investigation of an understudied clinical presentation; 2) by providing the first investigation of pathophysiology and risk mechanisms; and 3) by characterizing poorly understood longitudinal outcomes. In sum, conceptualizing avoidant/restrictive eating within an RDoC framework that integrates mind, brain, and behavior has great potential to reduce the burden of feeding disorders by informing nosology, treatment, and prevention.