The role of circadian rhythms in Obstructive Sleep Apnea symptoms and novel targets for treatment

ABSTRACT

Obstructive Sleep Apnea (OSA) is a common disorder that is associated with disability, premature mortality and lost quality of life. Excessive daytime sleepiness and depressive symptoms confer a great portion of the disability and lost quality of life associated with the disorder. While showing robust rates of response and symptoms resolutions, current treatments aimed at correcting the respiratory disturbances are not universally successful and a non-negligible proportion of patients who are correctly using available therapies do not experience symptomatic relief, suggesting that mechanisms beyond the respiratory disturbances may be involved in the pathogenesis of symptoms. A growing body of literature concerning animal and human models suggests that the sleep and respiratory disturbances commonly seen in OSA, namely sleep fragmentation, partial sleep deprivation, intermittent hypoxia, can promote shifts in circadian rhythms ultimately leading to misalignment between sleep-wake rhythms and the internal clock, as well as desynchrony amongst peripheral clocks and peripheral and central clock. This manuscript reviews the current evidence in support of a circadian disturbance underlying OSA symptomatology and proposes new applications for existing chronotherapeutic interventions with the potential for improving symptoms and quality of life for those patients that do not find symptomatic relief with currently available treatments.

KEYWORDS:

• Obstructive Sleep Apnea
• excessive daytime sleepiness
• circadian misalignment
• circadian disruption
• circadian desynchrony
• bright light therapy
• aerobic exercise

Acknowledgements

Dr Soreca is supported by the grant # 1 I21 RX003304-01 from the Department of Veterans Affairs, Rehabilitation Research and Development (RR&D).

Disclaimer

The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government.

Additional information

Funding

This work was supported by the Health Services Research and Development [1 I21 RX003304-01].