Research Links Molecular By-Products of the Steroid Hormone to Excessive Daytime Sleepiness
BOSTON — Most Americans, from pre-teens to elders, just don't get enough sleep, a lifestyle factor that has been linked to increased risk of death, high blood pressure, heart disease, car accidents and overall quality of life. Now, a new study sheds light on the biological underpinnings of excessive daytime sleepiness, a persistent and inappropriate urge to fall asleep during the day — during work, at meals, even mid-conversation — that interferes with daily functioning. The findings published in The Lancet eMedicine, open the door to exploring how nutrition, lifestyle and environmental exposures interact with genetic and biological processes to affect alertness.
"Despite its high prevalence and link to multiple health issues, much remains unknown about excessive daytime sleepiness," said co-corresponding author Tamar Sofer, PhD, director of Biostatistics and Bioinformatics at the Cardiovascular Institute at BIDMC, "Recent studies identified genetic variants associated with excessive daytime sleepiness, but genetics explains only a small part of the story. We wanted to identify biomarkers that can give stronger insights into the mechanisms of excessive daytime sleepiness, and help explain why some people experience persistent sleepiness even when their sleep habits seem healthy."
Investigators from Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women's Hospital (BWH) turned to metabolite analysis to better understand the biology behind excessive daytime sleepiness. Metabolites are small molecules produced as the body carries out its normal functions, from synthesizing hormones, to metabolizing nutrients to clearing environmental toxins. By measuring these metabolites (in a process known as large-scale metabolomics analysis), researchers created a profile of excessive daytime sleepiness.
The scientists analyzed blood levels of 877 metabolites in samples taken from more than 6,000 individuals in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a long-running study sponsored by the National Institutes of Health since 2006. When they cross-referenced these data with participants' self-reported measures of sleepiness on an official survey, investigators identified seven metabolites that were significantly linked with higher levels of excessive daytime sleepiness.
The seven metabolites turned out to be involved in the production of steroids and other biological processes already implicated in excessive daytime sleepiness. When the investigators looked only at data from male participants, an additional three metabolites were identified, suggesting there might be sex-based biological differences in how excessive daytime sleepiness manifests.
The findings add weight to the idea that excessive daytime sleepiness isn't just the result of too little sleep but can reflect physiological circumstances that might someday be diagnosed through blood tests or treated through targeted interventions.
"As we learn what's happening biologically, we are beginning to understand how and why EDS occurs, the early signs that someone might have it, and what we can do to help patients," said lead author Tariq Faquih, PhD, a postdoctoral research fellow in Sofer's lab and in the lab of Heming Wang, PhD, at BWH. "These insights could eventually lead to new strategies for preventing or managing sleep disorders that include daytime sleepiness as a major symptom."
Co-authors included Kaitlin S. Potts, Pavithra Nagarajan, Susan Redline, and co-corresponding author Heming Wang of Brigham and Women's Hospital; Bing Yu, Qibin Qi of the University of Texas Science Center at Houston; Robert Kaplan and Carmen R Isasi of Albert Einstein College of Medicine; Kent D. Taylor, Peter Y. Liu and Jerome I Rotter of Harbor-UCLA Medical Center; Satu J. Strausz and Hanna M Ollila of the Broad Institute; Tianyi Huang of National Institute on Aging; Russell P. Tracy of University of Vermont; Craig Johnson of University of Washington, Seattle; Stephen S. Rich, of University of Virginia, Charlottesville; Clary B Clish of Broad Institute of MIT and Harvard. Please see the publication for disclosures.
This work was supported by the National Institutes of Health (NIH) (grants R01HL153814 (to H.W.), R01HL161012 (to T.S.), and 7R01HL161012 (to S.R. and T.S.)); the National Institute on Aging (grant R01AG080598 supports T.S.). Support for metabolomics data was graciously provided by the JLH Foundation (Houston, Texas).
The Hispanic Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01- HC65236), and San Diego State University (N01-HC65237). Please see the publication for a complete list of Institutes/Centers/Offices that contribute to the HCHS/SOL through the National Heart, Lung, and Blood Institute (NHLBI).
