The role of the circadian system in binge eating disorder

项目总结 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 发展为一个独立的研究人员，将研究脑-身体沟通在精神病学中的作用 紊乱，重点是昼夜节律系统(CS)。这位候选人是一名精神病学家和神经科学博士。 K23建议的主要目标是：1)熟练掌握CS和暴饮暴食障碍 (BED)实验治疗学，2)增进对CS和BED的认识，3)增加补助金和 手稿写作技巧，以及4)发展研究网络。这些将通过高级培训来实现 在BED和CS研究和协作中，统计分析，手稿和赠款写作，并进行 关于床上CS的研究项目。Bed显示明显的昼夜节律特征，提示昼夜节律延迟 阶段，初步证据表明暴饮暴食可能对时间生物学干预有反应， 在其病理生理学上暗示存在CS功能障碍。仍然缺乏的是对 卧床CS功能障碍的特点，以及它是否代表一个治疗靶点。因此，总体来说， 研究策略的目标将是描述卧床CS功能障碍的特征，以及这种功能障碍 代表了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)对 在床的病理生理学中的作用，以及结合早晨来提前昼夜节律 强光(BLT)和夜间褪黑激素(MEL)将改善卧床症状。为实现总体目标，我们 我将在两个阶段追求以下具体目标(SA)：SA1)表征床上CS功能障碍 (第一阶段)。将对80名成年(18至50岁)肥胖者、40名卧床和40名不卧床的受试者进行CS功能评估 床上，在为期两周的观察阶段。我们的工作假设是DLMO(主要结果 测量)和次要昼夜节律参数(即运动活动峰期)将在床上稍后出现 与无卧床者比较，并将与卧床者的临床特征相关联。SA2)评估 昼夜节律相作为预测对时间生物学干预反应的生物标志物和CS的证据 目标是在床上参与(第二阶段)。一项为期4周的双盲随机假/安慰剂对照研究 采用设计评价BLT+MEL对40例成年肥胖者CS和饮食行为的影响 我们的工作假设是BLT+MEL将诱导 DLMO进展越大(主要结果衡量标准)，暴饮暴食天数/周减少越多(次要指标 结果衡量标准)。此外，较晚的基线DLMO(次要结果)将预测更大的下降 每周暴饮暴食的天数和代谢参数对BLT+MEL的反应。预期的结果是 应聘者完成总体目标并过渡到研究独立性。研究性学习 将表征CS在床上的功能障碍，并提供对CS在床上的机械性贡献的洞察 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.