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：
9244073
负责人：
Elizabeth Austen Lawson
金额：
$ 71.37万
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/9244073
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.

描述（由申请人提供）：回避和限制性饮食在青少年心理健康障碍中很常见，并且可能与生长不良、营养缺乏、精神症状和社会心理障碍有关。新推出的 DSM-5 回避/限制性食物摄入障碍包括。一些（但不是全部）回避性和限制性饮食表现表明，回避性和限制性饮食具有高度异质性，摄入不足的特点是窒息或呕吐恐惧症；此外，我们对其病理生理学或长期结果知之甚少，我们的研究将利用具有临床心理学、儿童精神病学、儿科专业知识的国际团队的独特和互补的贡献。我们将建立一个由 8-18 岁儿童 (n=100) 和健康对照组 (n=50) 匹配的临床队列。性别、年龄和坦纳阶段，以研究跨分析单元，RDoC 结构如何导致回避和限制性饮食。首先，我们捕获了负价（急性威胁/恐惧）过度活动（电路：在验证期间杏仁核激活）其次，我们发现恐惧范式；激素：皮质醇和催产素；生理学：心率和皮肤电导；自我报告：恐惧和特质焦虑。唤醒/调节（稳态）功能障碍（回路：经过验证的食物范式期间下丘脑和岛叶激活不足；激素：PYY、CKK、BDNF；自我报告：饥饿和饱腹感）将与食欲不振特征相关。第三，我们将探索认知系统。（感知）过度敏感（回路：味觉范式期间初级味觉皮层过度激活；激素：PYY；自我报告：感官概况；行为：味觉和气味阈值、辨别和检测；生理学：味觉感知）及其与感觉特征的相关性，我们预计临床队列在这 3 种结构上会出现比对照组更大的功能障碍。确定回避/限制性饮食是否包含多种不同的表型（如先前文献假设的）或具有 3 个重叠维度的单一表型（如我们所渴望的）我们将跟踪我们的临床队列 2 年来评估 a) 回避/限制性饮食的持续性。 ,生长和精神病理学结果；以及 b) 如果所有 3 个 RDoC 结构的功能障碍都可以预测结果，那么这项研究将在 3 方面具有创新性和独特性：1) 通过提供未充分研究的临床表现的实证研究；2) 通过提供首次调查；病理生理学和风险机制；3）通过描述人们知之甚少的纵向结果，总之，在整合思想、大脑和行为的 RDoC 框架内概念化回避/限制性饮食具有减轻负担的巨大潜力。通过告知疾病学、治疗和预防来了解喂养障碍。