Glucocorticoid enhancement of food exposure therapy in Binge Eating Disorder (GEAR)

背景资料：暴饮暴食症（BED）是最普遍的饮食失调，主要特征是无法控制的对食物的渴望和暴饮暴食的定期发作。虽然它可以有效地治疗认知行为疗法（CBT），约。25%的患者退出治疗，50%的患者复发。无法控制的对食物的渴望和随后的食物摄入可以被认为是对食物/进食的内部和外部线索的条件反应。食物暴露疗法与反应预防是BED CBT的重要组成部分，旨在通过重复的消退事件减少这种条件反应。在这个绝灭过程中，新的绝灭记忆被巩固。重要的是，临床前和临床研究表明，糖皮质激素可以促进这些记忆过程。糖皮质激素水平的增加抑制了情绪唤起记忆内容的提取，促进了记忆的巩固。这些效应已成功地用于改善焦虑症的暴露疗法。基于这些发现，似乎很有希望检查糖皮质激素对BED食物暴露疗法的记忆过程的潜在影响。方法：这是一项双盲、随机化、安慰剂对照的初步优效性试验，有两个平行治疗组。该项目的总体研究问题是，在BED中，糖皮质激素是否会增强食物暴露期间的消退学习。为此，将招募50名BED患者。在对进食障碍的精神病理学、食物摄入、特质和线索引起的食物渴望以及食物相关焦虑进行基线评估后，参与者将被随机分配接受三次食物暴露治疗，以及皮质醇或安慰剂。在干预期间和之后以及1个月后，将对参与者进行相同参数的重新评估。此外，分析STAT蛋白的酪氨酸磷酸化水平和DNA结合活性的变化将使我们能够更深入地了解免疫系统和消退学习之间的分子串扰。临床相关性和创新：计划中的研究将基础研究的结果转化为一种新的联合治疗方法。这将是第一个研究糖皮质激素对增强BED暴露疗法下的消退学习过程的潜在有益作用。如果成功的话，这将为这种疾病的治疗取得重大进展铺平道路。此外，在更广泛的层面上，这项研究将有助于丰富的糖皮质激素增强暴露治疗的作用机制的理解，通过研究参与这些过程的两个重要的基因转录因子的相互作用和协同性。

Background: Binge Eating Disorder (BED) is the most prevalent eating disorder and primarily characterised by uncontrollable craving for food and regular episodes of binge eating. Although it can be effectively treated by cognitive-behaviour therapy(CBT), approx. 25% of patients drop out from treatment and 50% experience relapse. The uncontrollable craving for food and subsequent food intake can be considered as conditioned responses to internal and external cues of food/eating. Food exposure therapy with response prevention is a crucial component of CBT for BED and aims to reduce such conditioned responses through repeated extinction events. During this extinction, new extinction memories are consolidated. Importantly, preclinical and clinical research has shown that these memory processes can be facilitated by glucocorticoids. Increased glucocorticoid levels inhibit the retrieval of emotionally arousing memory content and facilitate memory consolidation. These effects have been successfully utilised to improve exposure therapy for anxiety disorders. Based on these findings, it appears promising to examine the potential effects of glucocorticoids on memory processes underlying food exposure therapy for BED. Method: This is a double-blind, randomised, placebo-controlled pilot superiority trial with two parallel treatment arms. The overall research question of the project is whether in BED, glucocorticoids enhance extinction learning during food exposure. To this end, 50 patients with BED will be recruited. After baseline assessment of eating disorder psychopathology, food intake, trait and cue-elicited food craving, and food-related anxiety, participants will be randomly allocated to receive three sessions of food exposure therapy and either cortisol or placebo. During and after the intervention as well as 1 month later, participants will be re- assessed for the same parameters. In addition, analyses of changes in the tyrosine-phosphorylation level and DNA binding activity of STAT proteins shall enable a deeper understanding of the molecular cross-talk between the immune system and extinction learning. Clinical relevance and innovation: The planned study translates findings from basic research into a new combined treatment approach. It will be the first study to examine the potentially beneficial effects of glucocorticoids on the enhancement of extinction learning processes underlying exposure therapy for BED. If successful, thiscould pave the way for a significant improvement in the treatment of this disorder. Moreover, on a broader level, the study will contribute to an enriched understanding of the action mechanisms underlying glucocorticoid-augmented exposure therapy by studying the interactions and cooperativity of two important gene transcription factors involved in these processes.