NIH Sleep Research Plan Highlights Women’s Health, Reducing Disparities

February 15, 2022

By Deborah Borfitz

February 15, 2022 | In December the National Institutes of Health (NIH) released the latest version if its Sleep Research Plan that used a crowdsourcing campaign to ensure all willing voices on the topic were captured. The congressionally-mandated plan, the fourth in a series published since 1996, seeks to draw the attention of investigators to high-priority areas that could “make an impact within the next five to 10 years,” according to Marishka K. Brown, Ph.D., director of the National Center on Sleep Disorders Research (NCSDR). 

Among the major themes of the listed “critical opportunities” are the health of women and reducing sleep health disparities as it relates to risk, she says. But the research areas viewed as timely and actionable run the gamut from the impact of too little sleep on dementia risk and adolescent health and performance to the underlying mechanisms of fatigue and sleepiness. 

The latest NIH Sleep Research Plan debuted in mid-December and covers five enduring, big-picture strategic goals:

  • Elucidate the sleep and circadian mechanisms underlying health and disease
  • Improve the treatment of sleep and circadian disorders and reduce the risk associated with sleep deficiency and circadian misalignment
  • Identify gaps and opportunities to accelerate the clinical implementation of sleep and circadian research and protect public health
  • Advance the scientific understanding of sleep and circadian contributions to health disparities in diverse populations, and their different impacts on the public safety of these populations
  • Foster the development of a strong and diverse workforce for sleep and circadian research

Development of the plan began with a Sleep Disorders Research Board that holds public meetings three times a year to solicit input from patient advocacy groups, medical professionals, representatives from various NIH institutes and other federal agencies, and all other interested individuals, says Brown. A subsequent request for information elicited hundreds of emails and the information was collated and socialized before the IdeaScale crowdsourcing campaign was launched to further refine the plan.    

Arguably the highest priority area is development and identification of sleep and circadian rhythm biomarkers, Brown says, since “you can’t diagnose what you can’t measure.”

A perennial challenge, particularly in sleep medicine, is that a disease or disorder goes unrecognized until patients manifest symptoms, she continues. Biomarkers would enable earlier diagnosis and provide a means of tracking whether an intervention is working. 

The most useful biomarkers would be akin to blood pressure as a diagnostic for hypertension or an A1C test for diabetes, says Brown, and “may not necessarily be one number… [but] a panel or a signature.” Having an easy and accessible way to measure if individuals are sleep-deprived is a critical need not just in medicine but also aviation—i.e., if a pilot has gotten enough sleep to safely fly.

As has been widely reported, sleep problems have become more common during the ongoing COVID-19 pandemic (termed “coronasomnia”). But sleep has been a hot topic for decades now because everyone does it—ideally, for one-third of their life—and is not just a behavior but a physiological need like air and water that is required for overall health and functioning, Brown says.

Sex Bias

The NIH commonly crafts national goals, as do its multiple offices. Development of the Sleep Research Plan is a legislative mandate that accompanied creation of NCSDR by Congress per the NIH Revitalization Act of 1993, says Brown. But credit for its establishment goes to the sleep medicine community that impressed upon Congress that sleep disorders were a significant health and economic problem warranting national attention.

It has been 10 years since the last Sleep Research Plan was released and a lot has changed—including growing concern about sleep health disparities and sex biases in medical research, Brown continues. Like many diagnostics, the apnea hypopnea index (AHI) measuring the severity of obstructive sleep apnea was developed based on studies in “white males of a certain age, weight and demographic,” she offers as an example. 

“But now research has shown us that the parameters used for AHI may not necessarily work for women,” Brown notes. “What is considered mild sleep-disordered breathing in men can actually be moderate to severe in women, and… sleep apnea in premenopausal women is often not diagnosed because their symptoms could potentially be confused and confounded with societal factors [e.g., stress].” Common symptoms such as snoring and excessive daytime sleepiness also may be less likely in women. 

Women can consequently go on a lengthy “diagnostic odyssey” because their symptoms are not being recognized as associated with sleep apnea, she says. This in turn increases their cardiovascular risk, particularly as these women reach middle age. 

Luckily, for women in general, the NIH has had a “sex as a biological variable” policy that applies to all its funded research. “If you are doing [NIH-funded] research, you can no longer say we are not looking at female mice or women because of their estrogen cycle,” Brown shares. “We are half the population, sorry, [sex] is normal physiology, not a confounder.”

The Sleep Research Plan similarly shines a light on health disparities, an ongoing topic of conversation since the early 2000s, she adds. At a workshop in 2018, the NCSDR together with the National Office on Minority Health and Health Disparities, the National Heart, Lung, and Blood Institute, and the Office of Behavioral and Social Sciences Research explicitly defined sleep health disparities and created funding opportunities to help address them.

Overall, the Sleep Research Plan serves as guidance for research priorities and collaborations over the next several years and serves as a “springboard... to move the field forward,” Brown stresses. There will likely be specific, NIH-wide funding opportunities to stimulate research around some of the priorities outlines in the plan.

But investigator-initiated research constitutes 80% of NIH grant awards, she adds. The NIH has 27 institutes and centers and 24 of them fund research. Of those, 21 fund sleep and circadian biology research—in FY2020, to the tune of almost $500 million.

Sleep Deprivation 

The NIH Sleep Research Plan names a total of 69 critical research opportunities, and the association between sleep loss and dementia risk makes the list. As first reported a decade ago, the lymphatic system is twice as fast at clearing β-amyloid linked to Alzheimer’s disease from the brain during sleep than wakefulness.

In a 2018 paper published in PNAS (DOI: 10.1073/pnas.1721694115), research out of the lab of Nora Volkow, director of the National Institute on Drug Abuse, revealed a bidirectional relationship between β-amyloid accumulation and sleep. After just one night of sleep deprivation, the brain burden of β-amyloid significantly increases, says Brown, raising questions about the phenomenon over decades of chronic sleep deprivation. 

Research on the impact of too little sleep on adolescents has been growing, Brown continues, but still lacking are ways of predicting, detecting, and treating the problem to promote lifelong health and wellbeing and prevent disease. The circadian rhythms of teens are delayed, meaning “11 p.m. for adults can essentially be equated to 7 p.m. for adolescents.” 

Parents often try to drag their kids out of bed in the morning, thinking they’re lazy, but instead are unknowingly violating their biological clock, says Brown. And the sleep loss they experience has effects on both their health and performance.

For adolescents in under-represented and low socioeconomic status groups, the potential health disparities associated with sleep deprivation might negatively impact the trajectory of their career and life potential, she points out.

Connection Points

Another priority line of research in the plan is to elucidate the significance of sleep and circadian biology to immune function and the microbiome. Research over the past several years suggests a connection between metabolism and sleep and the importance of when, and not just what, people eat, Brown says.

Emerging research suggests that the gut microbiome itself experiences circadian and diurnal rhythms and that eating patterns—including time-restricted eating and meal frequency—can influence the risk of obesity and diabetes. “A lot more research needs to happen, but what is out there is really intriguing.”

The Sleep Research Plan also calls attention to the need to embed omics-based approaches in real-world healthcare settings to facilitate personalizing treatments and cures for sleep and circadian rhythm disorders. Sleep data can now be collected more comfortably, affordably, and on a larger scale from just about everywhere, says Brown, and that is allowing the research community to ask new and interesting questions. 

All that big data can also be leveraged via research tools, such as those provided by the National Sleep Research Resource of the NIH (sleepdata.org), to discover new pathways and treatment targets, she continues. The resource offers free access to a large collection of polysomnography and sleep data on research-derived patient cohorts in clinical trials, and members also contribute data and tools for sharing as well as suggestions on how to improve the exchange.

Healthcare providers are also capturing large amounts of digital data, which researchers could perhaps leverage in a deidentified form to create new opportunities to track people’s health or personalize interventions, says Brown. “We’ve been talking about precision medicine for a long time [and] using big data may be a way to actually do that and have it implemented in a real-world setting.” 

Shifting Gears

Adoption of more people-driven methods of promoting awareness of sleep and circadian rhythms and healthy sleep behaviors is another near-term goal in the Sleep Research Plan. Historically, researchers looking to engage communities tended to favor the top-down approach where they altruistically went about trying to help people “without really assessing the assets that those communities and people have,” Brown says. 

“Our idea about building awareness is… engaging people to then drive the research,” she adds, and requires a method that includes face-to-face dialogue and relationship-building. “Researchers that have successfully worked with the communities and formed these relationships have seen great results … we just need to do it at scale.” 

It might also be a good tactic for tackling sleep-related health disparities, which account for the bulk of the actionable research approaches in the overall Sleep Research Plan. According to the Centers for Disease Control and Prevention, minoritized and underrepresented populations bear a disproportionate burden of sleep loss that increases risks to their health, Brown says. 

The future of research into sleep health disparities requires understanding some of the socioeconomic, cultural, and environmental factors that impact disadvantaged communities, she adds, which is a significant step forward for this emerging area of research.  

The final strategic goal in the plan, to foster development of a diverse workforce for sleep and circadian research, has no associated critical opportunities listed. “It is really a call to action for the research communities to put these things into place,” says Brown, noting that the NIH is talking about diversity in terms of under-represented groups as well as different scientific areas.

“The need for sleep and circadian biology is not only for sleep and circadian researchers,” she says. It is connected to multiple specialty areas, including chronotherapy that optimizes the timing of drug administration. About three-quarters of all drugs that are approved by the Food and Drug Administration are circadian-regulated.