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

 描述（由申请人提供）：避免和限制性饮食在青少年心理健康疾病中很常见，并且与生长不良、营养缺乏、精神症状和心理社会障碍有关。新引入的DSM-5避免/限制性食物摄入障碍包括一些（但不是全部）避免和限制性饮食介绍。初步证据表明，回避型和限制型饮食是高度异质性的，摄入量不足的特点是窒息或呕吐恐惧症;对喂养失去兴趣;和/或极端的食物选择性。此外，关于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，儿科学，内分泌学，生物统计学和功能性神经影像学专业知识的国际团队的独特和互补贡献，以调查回避和限制性饮食的风险机制和纵向结果。 我们将建立一个8-18岁儿童（n=100）和健康对照组（n=50）的临床队列，这些儿童在性别、年龄和坦纳分期方面相匹配，以研究RDoC结构如何在分析单元中促进回避性和限制性饮食。首先，我们假设负价（急性威胁/恐惧）过度活动（回路：在有效的恐惧范式期间杏仁核激活;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）将与恐惧特征相关。第二，我们假设唤醒/调节（稳态）功能障碍（回路：在经过验证的食物范例期间下丘脑和垂体低活化;激素：PYY，CKK，BDNF;自我报告：饥饿和饱腹感）将与低食欲特征相关。第三，我们将探讨认知系统（感知）过度敏感（回路：在味觉范式期间初级味觉皮层的过度激活;激素：PYY;自我报告：感觉特征;行为：味觉和气味阈值，辨别和检测;生理学：味觉感知）及其与感官特征的相关性。我们预计，在这3种结构中，临床队列将比对照组具有更大的功能障碍。然后，我们将使用潜在的类因素模型，以确定是否回避/限制性饮食包括多个不同的表型（如以前的文献假设）或一个单一的表型与3个重叠的维度（如我们假设）。我们将随访我们的临床队列2年，以评估a）回避/限制性饮食、生长和精神病理学结局的持续性;和B）是否所有3种RDoC结构中的功能障碍都预测结局。本研究将在3个方面具有创新性和独特性：1）通过提供对未充分研究的临床表现的实证研究; 2）通过提供对病理生理学和风险机制的首次研究; 3）通过表征对纵向结局知之甚少的特征。总之，在RDoC框架内将回避/限制性饮食概念化，该框架整合了思想，大脑和行为，具有通过告知疾病分类学，治疗和预防来减轻喂养障碍负担的巨大潜力。

 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.