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

糖皮质激素增强暴食症食物暴露疗法（GEAR）

• 批准号: 442211733
• 负责人: Professor Dr. Timo Brockmeyer
• 金额: --
• 依托单位: Division of Cognitive Neuroscience
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/442211733?language=en
• 关键词: Glucocorticoid; enhancement; food; exposure; therapy

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.

背景：暴食症（BED）是最普遍的饮食失调症，主要特征是无法控制的对食物的渴望和经常性的暴食。虽然它可以通过认知行为疗法（CBT）有效治疗，但大约。 25% 的患者退出治疗，50% 的患者出现复发。对食物无法控制的渴望和随后的食物摄入可以被视为对食物/饮食的内部和外部线索的条件反应。预防反应的食物暴露疗法是暴食症 CBT 的重要组成部分，旨在通过重复的灭绝事件来减少这种条件反应。在这次灭绝期间，新的灭绝记忆被巩固。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。糖皮质激素水平升高会抑制唤起情绪的记忆内容的检索并促进记忆巩固。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，检查糖皮质激素对暴食症食物暴露疗法基础记忆过程的潜在影响似乎很有希望。方法：这是一项双盲、随机、安慰剂对照的试点优越性试验，有两个平行治疗组。该项目的总体研究问题是在暴食症中，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。在对饮食失调精神病理学、食物摄入量、特质和线索引起的食物渴望以及与食物相关的焦虑进行基线评估后，参与者将被随机分配接受三期食物暴露疗法以及皮质醇或安慰剂。干预期间和干预后以及 1 个月后，将重新评估参与者的相同参数。此外，对 STAT 蛋白酪氨酸磷酸化水平和 DNA 结合活性变化的分析将有助于更深入地了解免疫系统和灭绝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发现转化为新的联合治疗方法。这将是第一项研究糖皮质激素对增强暴食症暴露疗法基础的消退学习过程的潜在有益作用。如果成功，这将为显着改善这种疾病的治疗铺平道路。此外，在更广泛的层面上，该研究将通过研究参与这些过程的两个重要基因转录因子的相互作用和协同性，有助于丰富对糖皮质激素增强暴露疗法的作用机制的理解。