Circadian Rhythms

The purpose of this project is to improve our understanding of peripheral circadian rhythms in humans. Circadian clocks are present in most tissues of the body with importance for optimal physiological function, health, and behavior. This project will utilize simulated jetlag protocols to systematically test novel hypotheses about the regulation of peripheral circadian rhythms in humans. Specifically, we will examine how changes in the time of when we are exposed to light and the timing of when we eat impacts proteins in the blood and saliva that represent rhythms from clocks in the brain (e.g., rhythms of the hormones melatonin and cortisol coordinated by the brain) and rhythms from clocks in body tissues (e.g., proteins made by immune and bone cells, and cells in the stomach and liver). We also aim to discover new blood-based biomarkers of peripheral rhythms in humans. We anticipate our findings will be the first step in developing novel circadian based treatments for aligning peripheral clocks under conditions such as jetlag, and for developing novel circadian biomarkers that will advance our scientific understanding of circadian rhythms.

This study is a mechanistic clinical trial designed to investigate the effects of the circadian system and sleep on non-dipping blood pressure (BP) in people with hypertension (HTN).

The purpose of this study is to investigate whether the experience of a daily time delay can affect our internal circadian rhythm.

Opioid use disorder (OUD) is a chronic relapsing disorder and is well-known for its high-risk rate of overdoses and death. In OUD, sleep and circadian disruptions are highly prevalent, interfere with opioid maintenance treatment outcomes and increase the risk of relapse. So far, commonly used pharmacological sleep treatments fail to improve sleep or decrease illicit drug use in OUD. Thus, there is an urgent need to fill this research gap. Previous work showed that OUD patients who were receiving opioid agonist treatment (MOUD+) exhibited greater irregularity of sleep-wake cycle. In OUD patients, sleep-wake irregularity was associated with years of heroin use and low light exposure. Bright light therapy (BLT) is a very promising circadian/sleep intervention for several sleep, psychiatric and neurological disorders. BLT improved circadian, sleep outcomes and negative mood. In a pilot study, BLT improved objective and subjective sleep in patients with alcohol use disorder. Here investigators proposed an intervention study for MOUD+ patients to determine effects of BLT as an adjunct treatment on sleep and circadian outcomes including endogenous circadian rhythm, rest-activity rhythm and sleep neurophysiology (Primary objectives); and to determine effects of BLT on brain function and on clinical outcomes including negative affect, craving and illicit drug use and whether changes in sleep and circadian rhythm mediate the BLT effect on brain recovery and clinical outcomes (Secondary objectives). Fifty MOUD+ will be assigned either to bright light or to dim light group for 2 weeks. The groups will be matched for age, sex, race and OUD medication (Methadone vs Buprenorphine). The study will run throughout the year such that it occurs during all seasons. Light exposure will be measured with light sensor for additional control. All MOUD+ participants will have a daily 30-min light exposure (bright or dim blue light) in the morning after their habitual wake-up time and will be asked to avoid evening light before bed. Dim light melatonin onset, accelerometer, sleep EEG and questionnaires will be used to measure objective and subjective sleep and circadian outcomes. For brain function, cue-reactivity task will be used to assess brain activation during drug craving. Resting state functional connectivity and brain state dynamics will be assessed by rsfMRI. Mood, opiate craving and illicit drug use will be assessed. All measures will be repeated before and after the treatment. Investigators expect that BLT would normalize sleep and circadian outcomes, attenuate impairments in brain functions and result in better clinical outcomes. If successful, light therapy will provide add-on benefits to opioid agonist therapy and facilitate OUD recovery process.