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

摘要 避免进食和限制进食在青少年精神健康障碍中很常见，而且有可能是 与生长不良、营养不良、精神症状和社会心理障碍有关。 新推出的DSM-5《避免/限制性食物摄取障碍》包括部分(但不是全部) 避免进食和限制进食的陈述。初步证据表明，避免进食和限制进食 异质性很强的，摄入量很少，表现为窒息或呕吐恐惧症；对 喂食；和/或极高的食物选择性。此外，人们对它的病理生理或长期的- 期限结果。我们的研究将利用一个国际团队的独特和互补的贡献 拥有临床心理学、儿童精神病学、儿科、内分泌学、生物统计学和功能医学的专业知识 神经成像研究避免进食和限制进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。 性别、年龄和Tanner阶段相匹配，以调查RDoC如何跨分析单位构建 有助于避免和限制饮食。首先，我们假设负价(严重威胁/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；生理学：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。其次，我们假设唤醒/调节(内稳态)功能障碍(回路： 下丘脑和脑岛在有效食物范例中的低活性；激素：PYY、CKK、BDNF； 自我报告：饥饿和饱满)将与食欲低下的特征相关。第三，我们将探索认知 系统(知觉)过度敏感(回路：味觉期间初级味觉皮质过度激活 范式；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)及其与感官特征的相关性。我们预计， 临床队列在这三种结构上的功能障碍将比对照更严重。然后我们将使用潜伏期 确定避免进食/限制进食是否包括多种不同表型的阶级因素模型 (如先前的文献假设)或具有3个重叠维度的单一表型(如我们假设的)。我们 将跟踪我们的临床队列两年，以评估a)避免/限制进食、生长、 和精神病理学结果；以及b)如果所有三种RDoC结构的功能障碍都能预测结果。 这项研究将在三个方面具有创新性和独特性：1)通过对 临床表现研究不足；2)通过提供病理生理学和风险的第一次调查 机制；以及3)通过描述知之甚少的纵向结果。总而言之，概念化 在RDoC框架内整合了思维、大脑和行为，避免/限制饮食有很大的好处 通过告知病因学、治疗和预防，有可能减轻喂养障碍的负担。

ABSTRACT 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.