The role of the circadian system in binge eating disorder

点击翻译按钮获取中文摘要

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.