The role of the circadian system in binge eating disorder

昼夜节律系统在暴食症中的作用

• 批准号: 10611479
• 负责人: Francisco Romo-Nava
• 金额: $ 20.08万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611479
• 关键词: Adult; Age; Agonist; Applications Grants; Binge Eating; Binge eating disorder; Body mass index; Brain; Bulimia; Characteristics; Chronobiology; Circadian Rhythms; Clinical; Collaborations; Communication; Control Groups; Data; Diet Habits; Doctor of Philosophy; Double-Blind Method; Eating; Eating Behavior; Eating Disorders; Food; Fostering; Functional disorder; Gender; Goals; Grant; Health; Hypothalamic structure; Individual; Intervention; Investigational Therapies; Knowledge; Light; Manuscripts; Matched Group; Medical; Melatonin; Mental disorders; Mentors; Metabolic; Motor Activity; Neurosciences; Obesity; Outcome; Outcome Measure; Pathway interactions; Peripheral; Phase; Physiological; Physiological Processes; Placebos; Proxy; Psychiatrist; Psychopathology; Randomized; Reporting; Research; Research Design; Research Personnel; Research Project Grants; Role; Sleep; Statistical Data Interpretation; Symptoms; System; Time; Training; Translational Research; Writing; adult obesity; career development; circadian; comorbidity; discrete time; experience; improved; insight; light effects; loss of control over eating; new therapeutic target; obese person; patient oriented research; placebo controlled study; placebo group; predictive marker; primary outcome; research study; response; response biomarker; secondary outcome; skills; suprachiasmatic nucleus; systems research; therapeutic target

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.

项目概要 这项 K-23 提案的长期目标是推进 Romo-Nava 博士以患者为中心的研究事业 发展成为一名独立研究者，研究脑体通讯在精神病学中的作用 疾病，重点关注昼夜节律系统（CS）。该候选人是一名精神病学家和神经科学博士。 该 K23 提案的主要目标是： 1) 熟练掌握 CS 和暴食症 (BED) 实验疗法，2) 增强对 CS 和 BED 的了解，3) 增强资助和 稿件写作技巧，4) 发展研究网络。这些将通过高级培训来实现 从事 BED 和 CS 研究与合作、统计分析、手稿和资助写作，并进行 BED 中的 CS 研究项目。 BED 显示出显着的昼夜节律特征，表明昼夜节律延迟 阶段，初步证据表明暴饮暴食可能对时间生物学干预有反应， 暗示 CS 功能障碍与其病理生理学有关。仍然缺乏的是全面的知识 BED 中 CS 功能障碍的特征，以及它是否代表治疗目标。因此，总体 研究策略的目标是描述 BED 中 CS 功能障碍的特征，以及这种功能障碍是否 代表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 在 BED 病理生理学中的作用，以及通过早晨的结合来推进昼夜节律阶段 亮光 (BLT) 和夜间褪黑激素 (MEL) 将改善暴食症症状。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)： SA1) 描述 BED 中 CS 功能障碍的特征 （第一阶段）。 CS 功能将在 80 名成年（18 至 50 岁）肥胖受试者中进行评估，其中 40 名患有暴食症，40 名没有暴食症 BED，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（即运动活动末相）将在 BED 稍后出现 组与没有 BED 的组相比，并且将与 BED 临床特征相关。 SA2) 评估 昼夜节律阶段作为对时间生物学干预反应的预测生物标志物和 CS 的证据 BED 的目标参与度（第 2 阶段）。为期 4 周的双盲、随机、假手术/安慰剂对照研究 将利用设计来评估 BLT+MEL 对 40 名成人肥胖者的 CS 和饮食行为的影响 已完成第一阶段的 BED 受试者。我们的工作假设是 BLT+ MEL 会诱导 DLMO 进步越大（主要结果指标），暴食天数/周的减少幅度越大（次要指标） 结果测量）。此外，较晚的基线 DLMO（次要结果）将预测 暴食天数/周以及 BLT+MEL 的代谢参数。预期结果是 候选人完成总体目标并过渡到独立研究。研究研究 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目标的潜力。

项目成果

Insulin resistance in bipolar disorder: A systematic review of illness course and clinical correlates.

双相情感障碍的胰岛素抵抗：对病程和临床相关性的系统评价。

• DOI: 10.1016/j.jad.2023.04.068
• 发表时间: 2023
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Miola,Alessandro;Alvarez-Villalobos,NeriA;Ruiz-Hernandez,FernandoGerardo;DeFilippis,Eleanna;Veldic,Marin;Prieto,MiguelL;Singh,Balwinder;SanchezRuiz,JorgeA;Nunez,NicolasA;Resendez,ManuelGardea;Romo-Nava,Francisco;McElroy,Susa
• 通讯作者: McElroy,Susa

Diagnosing and treating major depressive episodes that lie along the mood disorders spectrum: focus on depression with mixed features.

诊断和治疗属于情绪障碍谱系的重度抑郁发作：重点关注具有混合特征的抑郁症。

• 发表时间: 2021
• 期刊: CNS spectrums
• 影响因子: 3.3
• 作者: McElroy,SusanL;Guerdjikova,AnnaI;Romo-Nava,Francisco
• 通讯作者: Romo-Nava,Francisco

Revisiting the bipolar disorder with migraine phenotype: Clinical features and comorbidity.

重新审视具有偏头痛表型的双相情感障碍：临床特征和合并症。

• DOI: 10.1016/j.jad.2021.08.026
• 发表时间: 2021
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Romo-Nava,Francisco;Blom,Thomas;Cuellar-Barboza,AlfredoB;Awosika,OluwoleO;Martens,BrianE;Mori,NicoleN;Colby,ColinL;Prieto,MiguelL;Veldic,Marin;Singh,Balwinder;Gardea-Resendez,Manuel;Nunez,NicolasA;Ozerdem,Aysegul;Biernacka
• 通讯作者: Biernacka

Study protocol and rationale for a randomized, placebo-controlled trial of solriamfetol to treat binge eating disorder.

solriamfetol 治疗暴食症的随机、安慰剂对照试验的研究方案和基本原理。

• DOI: 10.1016/j.cct.2021.106587
• 发表时间: 2021
• 期刊: Contemporary clinical trials
• 影响因子: 2.2
• 作者: Guerdjikova,AnnaI;Romo-Nava,Francisco;Blom,ThomasJ;Mori,Nicole;McElroy,SusanL
• 通讯作者: McElroy,SusanL

Clinical and Genetic Correlates of Bipolar Disorder With Childhood-Onset Attention Deficit Disorder.

• DOI: 10.3389/fpsyt.2022.884217
• 发表时间: 2022
• 期刊: FRONTIERS IN PSYCHIATRY
• 影响因子: 4.7
• 作者: Nunez, Nicolas A.;Coombes, Brandon J.;Romo-Nava, Francisco;Bond, David J.;Vande Voort, Jennifer;Croarkin, Paul E.;Leibman, Nicole;Gardea Resendez, Manuel;Veldic, Marin;Betcher, Hannah;Singh, Balwinder;Colby, Colin;Cuellar-Barboza, Alfredo;Prieto, Miguel;Moore, Katherine M.;Ozerdem, Aysegul;McElroy, Susan L.;Frye, Mark A.;Biernacka, Joanna M.
• 通讯作者: Biernacka, Joanna M.