Pathophysiology of Circadian Rhythm Delayed Sleep Wake Phase Disorder

PROJECT SUMMARY/ABSTRACT Delayed sleep-wake phase disorder (DSWPD) is a circadian rhythm disorder that impacts millions of Americans resulting in adverse health and performance consequences. Patients with DSWPD often obtain insufficient sleep during the work/school week due to difficulties falling asleep and awakening at socially required times, and patients present with excessive sleepiness that significantly interferes with daytime function. Current practice parameter guidelines and metanalyses consider existing treatment strategies for DSWPD, include morning light exposure, evening exogenous melatonin and chronotherapy to be ineffective/“weak” perhaps due to limited understanding of DWSPD pathophysiology and compliance. The overall goal of this proposal is to improve our understanding of DSWPD pathophysiology, which will inform development of new circadian based treatment strategies to improve the health, performance, and well-being of patients with DSWPD. We will conduct ambulatory and baseline circadian phase assessments prior to two in-lab circadian protocols to address our aims: 1) a constant routine protocol to precisely assess the circadian amplitude and phase of central and peripheral circadian rhythms, and 2) a nighttime light exposure protocol to examine cognitive and physiological responses. We will also determine if circadian phase can be accurately predicted in patients with DSWPD using a novel biomarker of circadian phase. Preliminary data from our basic human circadian and clinical trial research set the stage for this proposal. Our overall goal and aims support the NIH Precision Medicine Initiative, the 2021 National Institutes of Health Sleep Research Plan, and the NHLBI Strategic Vision plan.