Molecular Endocannabinoid Mediators of Impaired Aversive Learning in Low Weight Eating Disorders

项目概要： 低体重进食障碍（LW-ED），包括神经性厌食症和相关的非典型变异， 以持续的食物回避为特点。LW-ED患者的行为障碍持续存在 从急性饥饿阶段进入体重正常化阶段，观察到食物异常， 提示学习、与食物相关的期望和食物选择。我们假设， 情感和食物提示学习是由内源性大麻素（eCB）音调的非稳态破坏引起的，具体来说， 通过eCB 1受体的上调和eCB的反应性和张力受损来证明。这项建议 因此，旨在使用新型PET配体[（18）F]MK-9470来测试这一理论，这是一种稳健可靠的测量方法， 6名最近从LW-ED恢复体重的女性和6名年龄、性别和 体重指数与对照组女性相匹配。参与者将完成食物线索学习的行为测量 和食物选择，CB 1受体可用性的PET测量，血浆eCB的时间过程变化， 可口的食物挑战，客观和主观的饮食行为的措施。我们将：（1）建模两者 区域特异性和全脑测量eCB 1受体的可用性，和（2）测试eCB 1受体是否 将LW-ED患者与健康对照区分开来。此外，我们将评估这种上调是否介导了 血浆eCB对食物激发的时程反应受损。这项研究的结果将提供关键的 关于eCBs在LW患者的食物选择和避免的病理模式中的独特作用的数据- EDs.本研究的成功完成将为新型治疗干预提供切实可行的目标 药物、营养或联合治疗LW-ED患者。

Project summary: Low weight eating disorders (LW-EDs), including anorexia nervosa and related atypical variants, are characterized by persistent food avoidance. Disturbances in behavior among individuals with LW-EDs persist beyond the acute starvation stage into the period of weight normalization, with abnormalities observed in food- cue learning, expectancies related to food, and food choice. We hypothesize that the persistence of disordered affect and food-cue learning result from an allostatic disruption of endocannabinoid (eCB) tone, as specifically evidenced by an upregulation of eCB1 receptors and an impaired responsivity and tone of eCBs. This proposal therefore aims to test this theory using the novel PET ligand [(18)F]MK-9470, a robust and reliable measure of brain eCB1 receptor availability in 6 women recently weight restored from a LW-ED and 6 age, gender, and body mass index matched control women. Participants will complete behavioral measures of food-cue learning and food choice, PET measures of CB1 receptor availability, time course changes in plasma eCBs to a palatable food challenge, and objective and subjective measures of eating behavior. We will: (1) model both region specific and whole brain measures of eCB1 receptor availability, and (2) test whether eCB1 receptor discriminates those with LW-EDs from healthy controls. Further, we will evaluate if this upregulation mediates impaired time course response of plasma eCBs to food challenge. Results from this study will provide critical data about the unique role of eCBs in pathological patterns of food choice and avoidance in those with LW- EDs. Successful completion of this study will offers a tangible and robust target for novel treatment intervention with pharmacological, nutritional, or combination therapeutics among those with LW-EDs.