The role of the circadian system in binge eating disorder

项目摘要 这项K-23提案的长期目标是推进Romo-Nava博士以患者为导向的研究事业 发展为一个独立的调查员，将研究脑-体通信在精神病中的作用， 疾病，重点是昼夜节律系统（CS）。候选人是一名精神科医生和神经科学博士。 这个K23建议的主要目标是：1）掌握CS和暴食症的熟练程度 (BED)实验疗法，2）提高对CS和BED的知识，3）提高补助金， 论文写作技巧; 4）建立研究网络。这些将通过高级培训来实现 在BED和CS研究与合作，统计分析，手稿和赠款写作，并进行 研究项目的CS在床上。BED显示出明显的昼夜节律特征，表明昼夜节律延迟 阶段，初步证据表明，暴饮暴食可能是对时间生物学干预的反应， 表明CS功能障碍与其病理生理学有关。现在还缺乏的是对 BED中CS功能障碍的特征，以及它是否代表治疗靶点。因此整体 研究策略的目的是描述BED中CS功能障碍的特征，以及这种功能障碍是否 是一个潜在的治疗靶点我们的中心假设是，CS功能障碍（相位延迟）起着重要作用。 在BED的病理生理学中的作用，以及与早晨和夜间睡眠相结合 明亮的光线（BLT）和夜间褪黑激素（MEL）将改善BED症状。为了实现总体目标，我们 将分两个阶段追求以下具体目标（SA）：SA 1）表征BED中的CS功能障碍 （第1阶段）。将在80名成人（18至50岁）肥胖受试者中评价CS功能，其中40名患有BED，40名没有BED 在为期两周的观察期内，我们的工作假设是DLMO（主要结果） 测量）和次级昼夜节律参数（即，运动活动高峰期）将发生在床上晚些时候 组与无BED组比较，并将其与BED的临床特征相关联。SA 2）评价 昼夜节律时相作为对时间生物学干预和CS证据反应的预测生物标志物 在BED（第2阶段）的目标参与。一项为期4周的双盲、随机化、假手术/安慰剂对照研究 本研究采用随机对照设计，评价BLT+MEL对40例肥胖成年人CS和进食行为的影响 已完成1期研究的BED受试者。我们的工作假设是，BLT+ MEL将诱导 DLMO进展更大（主要结局指标），暴饮暴食天数/周减少更多（次要 结果测量）。此外，较晚的基线DLMO（次要结局）将预测 暴食天数/周和代谢参数对BLT+MEL的响应。预期的结果是， 候选人完成总体目标并过渡到研究独立。研究性学习 将描述BED中CS功能障碍的特征，并深入了解CS对BED的机制贡献 精神病理学及其作为治疗靶点的潜力。

PROJECT SUMMARY The long-term goal of this K-23 proposal is to advance Dr. Romo-Nava’s patient-oriented research career development as an independent investigator that will study the role of brain-body communication in psychiatric disorders, focusing on the circadian system (CS). The candidate is a Psychiatrist and PhD in neuroscience. The main objectives of this K23 proposal are to: 1) acquire proficiency in CS and binge eating disorder (BED) experimental therapeutics, 2) enhance knowledge on the CS and BED, 3) enhance grant and manuscript writing skills, and 4) develop a research network. These will be achieved through advanced training in BED and CS research and collaboration, statistical analysis, manuscript and grant writing, and conducting a research project on the CS in BED. BED shows prominent circadian features that suggest a delay in circadian phase, and preliminary evidence shows binge eating may be responsive to chronobiological interventions, implicating a CS dysfunction in its pathophysiology. What remains lacking is comprehensive knowledge of the characteristics of CS dysfunction in BED, and whether it represents a therapeutic target. Therefore, the overall objective of the research strategy will be to characterize CS dysfunction in BED and whether this dysfunction represents a potential therapeutic target. Our central hypothesis is that a CS dysfunction (phase delay) plays a role in the pathophysiology of BED, and that advancing the circadian phase with a combination of morning bright light (BLT) and nightly melatonin (MEL) will improve BED symptoms. To attain the overall objectives, we will pursue the following specific aims (SA) in two phases: SA1) To characterize CS dysfunction in BED (Phase 1). CS function will be evaluated in 80 adult (18 to 50 yrs) obese subjects, 40 with BED and 40 without BED, during a two-week observational phase. Our working hypothesis is that DLMO (the primary outcome measure) and secondary circadian parameters (i.e., locomotor activity acrophase) will occur later in the BED group compared with those without BED, and will be associated with BED clinical features. SA2) To evaluate circadian phase as a predictive biomarker for response to a chronobiological intervention and evidence of CS target engagement in BED (Phase 2). A 4-week double-blinded, randomized, sham/placebo controlled study design will be utilized to evaluate the effect of BLT+MEL on the CS and eating behavior in 40 adult obese subjects with BED who have completed phase 1. Our working hypothesis is that BLT+ MEL will induce a greater DLMO advance (primary outcome measure), a greater decrease in binge eating days/week (secondary outcome measure). In addition, a later baseline DLMO (secondary outcome) will predict a greater decrease in binge eating days/week and metabolic parameters in response to BLT+MEL. The expected outcomes are that the candidate completes the overall objectives and transitions to research independence. The research study will characterize CS dysfunction in BED and provide insight into the mechanistic contribution of the CS to BED psychopathology and its potential as a therapeutic target.