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

 描述(由申请人提供)：避免进食和限制进食在青少年精神健康障碍中很常见，并可能与生长不良、营养不良、精神症状和心理社会障碍有关。新推出的DSM-5《避免/限制食物摄取障碍》包括一些(但不是全部)避免和限制进食介绍。初步证据表明，避免进食和限制进食是高度不同的，摄入量很少，表现为窒息或呕吐恐惧症；对进食失去兴趣；和/或极端的食物选择性。此外，人们对其病理生理学或长期结果知之甚少。我们的研究将利用一个在临床心理学、儿童精神病学、儿科、内分泌学、生物统计学和功能神经成像方面的专业知识的国际团队的独特和互补的贡献，以调查避免和限制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(n=50)的临床队列，在性别、年龄和Tanner阶段相匹配的情况下，研究RDoC结构如何有助于避免和限制饮食。首先，我们假设负值(急性威胁/恐惧)过度活动(回路：在有效的恐惧范式中杏仁核激活；激素：皮质醇和催产素；生理：心率和皮肤电导；自我报告：恐惧和特质焦虑)将与恐惧症特征相关。其次，我们假设唤醒/调节(内稳态)功能障碍(回路：在有效的食物范例中下丘脑和脑岛活性低下；激素：PYY、CKK、BDNF；自我报告：饥饿和饱满)将与低食欲特征相关。第三，我们将探索认知系统(感知)过度敏感性(回路：味觉范式期间初级味觉皮质的过度激活；荷尔蒙：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)及其与感觉特征的相关性。我们预计临床队列在这三种结构上会比对照有更大的功能障碍。然后，我们将使用潜在的类别因素模型来确定回避性/限制性进食是否包括多个不同的表型(如先前文献所假设的那样)或具有3个重叠维度的单一表型(如我们所假设的)。我们将跟踪我们的临床队列两年，以评估a)回避性/限制性进食、生长和精神病理结果的持久性；以及b)所有三种RDoC结构的功能障碍是否预测结果。这项研究将在三个方面具有创新性和独特性：1)通过提供对未被充分研究的临床表现的实证研究；2)通过提供第一个病理生理学和风险机制的研究；以及3)通过表征鲜为人知的纵向结果。总之，在RDoC框架内将回避性/限制性饮食概念化，整合了思维、大脑和行为，通过告知病因学、治疗和预防，具有极大的潜力来减轻喂养障碍的负担。

 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.