Kappa Opioid Receptor Imaging in Anorexia

描述（由申请人提供）：神经性厌食症（AN）是一种严重的精神疾病，其特征在于两个主要特征：（a）与进食相关的强烈厌恶，导致难以维持健康体重，（B）与避免食物、进食或体重增加相关的快乐。在活动性AN患者中，甚至在体重恢复（AN-REC）的AN患者中，动机-奖励系统的紊乱都有很好的记录。理论上，特质焦虑和伤害回避的紊乱与血清素和多巴胺的紊乱有关。然而，进食行为受到阿片系统的严格调节，特别是在压力条件下。我们的提议验证了一个关于压力作用的新理论 和内源性阿片样物质的功能在AN的主要特征。AN的饥饿特征作为慢性应激源在疾病的早期阶段升高内源性阿片类物质。然而，阿片系统适应这种慢性压力，并创造了一种独特的阿片系统，其功能很像成瘾中发现的戒断状态。成瘾研究表明，κ阿片受体介导药物依赖个体的应激诱导复发。因此，我们将饥饿概念化为药物，将AN-REC概念化为AN过程中的戒断状态。这个模型为为什么AN患者的复发率如此之高提供了一个可检验的假设。我们将招募7名最近（< 1岁）体重从AN恢复的成年无药物女性和7名健康年龄和体重匹配的对照（HC）参与PET研究，使用新型PET示踪剂用于κ阿片受体（KOR）。受试者将完成食物回避的实验室测量和基于食物奖励的逆转学习任务。我们有三个具体目标：（1）检验AN-REC和HC之间KOR密度的组间差异;（2）检验下丘脑、杏仁核和下丘脑中KOR密度与实验室和自我报告的食物回避测量之间的相关性;（3）检验动机-奖励回路中KOR密度与逆向学习任务和情绪心理生理测量的相关性。将在AN-REC和HC中糖皮质激素功能与KOR水平之间关系的探索性分析中测量应激激素和阿片肽（ACTH、皮质醇、β-内啡肽）。本研究的结果将用于确定可用于预防AN-REC患者复发的新型药物治疗，并确定可能有助于解释AN患者复发风险的生物标志物。

DESCRIPTION (provided by applicant): Anorexia nervosa (AN) is a serious mental illness that is characterized by two primary features: (a) intense disgust associated with eating leading to difficulty maintaining healthy weight, (b) pleasure associated with avoidance of food, eating, or weight gain. Disturbances in the motivation-reward system are well documented in patients with active AN and even in those with AN who have achieved weight restoration (AN-REC). Disturbances in trait anxiety and harm avoidance have been theoretically linked to disturbances in serotonin and dopamine. However, eating behavior is tightly regulated by the opioid system particularly under conditions of stress. Our proposal tests a novel theory about the role of stress and endogenous opioid function in the primary features of AN. Starvation characteristic of AN acts as a chronic stressor elevating endogenous opioids in the early stages of the illness. However, the opioid system adapts to this chronic stress and creates a unique opioid system that functions much like a withdrawal state found in addiction. Research on addictions suggests that the kappa-opioid receptor mediates stress induced relapse among drug dependent individuals. Thus, we conceptualize starvation as the drug and AN-REC as the withdrawal state in the course of AN. This model provides a testable hypothesis for why relapse rates among those with AN are so high. We will recruit 7 adult medication free women recently (< 1 yr) weight restored from AN and 7 healthy age and weight matched controls (HCs) to participate in a PET study using a novel PET tracer for the Kappa-opioid receptor (KOR). Subjects will complete laboratory measures of food avoidance and a food-reward based reversal learning task. We have three specific aims: (1) To test for group differences in the density of KORs between AN-REC and HCs; (2) To test the correlations between KOR density in insula, amygdala, and hypothalamus and laboratory and self-report measures of food avoidance; (3) To test the correlations between KOR density in motivation- reward circuits and performance on a reversal learning task and psychophysiological measures of emotion. Stress hormones and opioid peptides (ACTH, cortisol, beta-endorphin) will be measured in an exploratory analysis of the relationship between glucocorticoid function and KOR levels among AN-REC and HC. Results from this study will be used to identify novel pharmacological treatments that may be used to prevent relapse among AN-REC patients and identify biomarkers that may help explain relapse risk among those with AN.