Evaluating the Circadian Response to Light in Delayed Sleep-Wake Phase Disorder

Cardiometabolic disease (CMD) is the leading cause of mortality worldwide. There is growing evidence that circadian dysregulation represents a modifiable risk factor for CMD. Later sleep timing has been associated with increased body mass index and poorer glycemic control. Thus, interventions aimed at circadian entrainment may be beneficial for modifying CMD risk. Understanding the causes of circadian dysregulation is key for this goal. Using delayed sleep-wake phase disorder (DSWPD) as a model system for circadian dysregulation the overall aim of this proposal will be to test the hypothesis that an altered ability to respond to light plays a role in the underlying pathophysiology of DSWPD. This will be tested by assessing the circadian response to light by measuring the phase response curve to light in individuals with DSWPD, and by evaluating function of the intrinsically photoreceptive retinal ganglion cells through assessment of the pupillary light response. By better understanding the mechanisms of impaired entrainment in these individuals, we will gain a better understanding of the physiology of the human circadian system, leading to targeted interventions for individuals with DSWPD, and the larger population of individuals with delayed circadian phenotypes, in turn mitigating the comorbid increased CMD risk accompanying this phenotype.