The National Center on Sleep Disorders Research—progress and promise

Mounting scientific evidence links sleep deficiency and sleep disorders to pathobiology in almost every human tissue. Chronic disease and lifestyle factors (e.g. work schedules) are associated with sleep deficiency, disruptions in circadian rhythm, and residual fatigue in an estimated 15%–30% of the general adult population. Economic analyses indicate that the US sustains the highest economic losses world-wide ($411 billion annually, or about 2.3% of gross domestic product) from the repercussions of sleep deficiency including disease burden, lost productivity and accidents, and an array of social determinants underlying health and health disparities [1].

In growing recognition of the toll that sleep deficiency and sleep disorders exact on productivity, morbidity, and mortality, Congress established the National Center on Sleep Disorders Research (NCSDR) within the National Institutes of Health (NIH), and National Heart, Lung, and Blood Institute (NHLBI) in 1993 [2]. As we approach the quarter-century mark since its creation, it is timely to reflect on the progress of a collaborative, community-engaged approach to public education, discovery, and translational science that portends unparalleled opportunities for sleep and circadian research in the future.

Public Education for Public Health Impact

Community involvement as the foundation of the NCSDR was formally incorporated through the legislative establishment of a Sleep Disorders Research Advisory Board to provide guidance to NIH on research gaps and directions. These scientific discussions have guided community engagement including the development of health education resources, public service announcements, and coordination with other federal agencies in critical domains, such as the prevention of sudden infant death and motor vehicle accidents. Several key highlights below demonstrate the efforts facilitated by the NCSDR in its first decade that were critical to increasing public knowledge related to sleep and health.

• The “Back to Sleep” campaign, a collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), is credited with saving thousands of newborn lives annually.

• Increased attention to the dangers of drowsy driving was initiated in collaboration with the Department of Transportation [3].

• Production of a NIH Sleep Neurobiology Curriculum featuring novel internet-based activities disseminated to school systems nation-wide to educate students on the importance of sleep health was performed in collaboration with the NIH Office of Science Education [4].

• The acclaimed five-year Garfield Star Sleeper campaign was another collaboration with NCSDR that targeted school-age children with carefully validated health messages linking sleep, education, and sports performance using age-appropriate coloring pads, online videogames, a Star-Sleeper costumed Garfield cat, and guidance to health educators [5].

Pivoting toward the creation of a data-guided research agenda, the NCSDR in its second decade enabled foundational surveillance capacity and launched an evidence review to better define the scope of the sleep health problem. The Centers for Disease Control and Prevention, National Health and Nutrition Examination Survey led the first surveillance of sleep health problems nation-wide. To complement the data gathered from surveillance, in 2006, NCSDR and community partners commissioned an assessment of progress by the Institute of Medicine (IOM). The IOM report concluded that sleep deprivation and disorders remain an unmet challenge to public health [6] and identified a spectrum of needs, including research training and educational tools supporting professional and public awareness. To meet these needs, NHLBI supports novel institutional training programs (T32) for sleep research, and educational research programs [7] to develop portable strategies to increase sleep health awareness among professionals, trainees, and the public.

These efforts led to a transformation in public awareness with increased recognition of sleep deficiency and untreated sleep disorders as a credible issue for public health and safety. At a landmark Frontiers of Knowledge NIH national conference in 2004, US Surgeon General Richard Carmona, MD, declared “It is essential that we get the public and health care professionals talking about sleep and the effects of insufficient sleep and sleep disorders.” [8]

Synergy Through Government Engagement and Coordination

By its nature, sleep research requires a coordinated, multidisciplinary approach to understanding sleep biology and disorders as well as the broad multisystem implications. NCSDR has served as the hub for sleep research coordination facilitated through an NIH-wide Sleep Research Coordinating Committee. Over the past 2–3 decades, a steadily increasing number of NIH Institutes and Centers have led workshops to inform the sleep research agenda. These workshops and collaborations have fostered new directions in sleep science including the intersection with health disparities (NHLBI-led), pain (NCCIH-led), diabetes (NIDDK-led), chrono-medicine (NCI-led), pregnancy (NICHD-led), and light (NIEHS-led).

Expanding the breadth of collaboration across a growing number of governmental venues, the NCSDR facilitated important sleep research activities into missions with broader implications on daily life. For example, NCSDR collaborations across DHHS led to the incorporation of “Sleep Health” as a topic area within the Healthy People initiative with national health objectives and benchmarks [9]. NCSDR outreach to the Department of Transportation, Department of Defense, and National Aeronautics and Space Administration led to several key milestones and accomplishments—from the development of a new drowsy driving prevention agenda by the National Highway Transportation and Safety Administration [10] to the development of policies ensuring public safety and military readiness. These activities laid the foundation for the recent identification of the “performance triad,” which now includes sleep as a third leg alongside diet and exercise [11].

These federal collaborative activities have brought about a unified recognition of the need to quantify the sleep-related health status of individuals and overcome barriers to conducting clinical research, a priority echoed in a biomarker development workshop jointly organized by NCSDR, NIA, and the Sleep Research Society [12]. The ability to measure sleep and circadian health status would facilitate the spectrum of biomedical sleep research, open the door to personalized medicine [12], and transform policies protecting public safety. Discussion with NIH, federal agencies, and potential third-party partners to substantially facilitate this avenue of research development are ongoing and a top priority for NCSDR.

Transformative Discovery Science

The stakeholder engagement and collaborative synergies that successfully expanded the public’s awareness about sleep as a major public health issue also set the stage for the NCSDR to engage the community to advance sleep and circadian discovery science. The inaugural NIH Sleep Disorders Research Plan in 1996 guided several landmark research initiatives including Specialized Centers of Research (SCOR), epidemiological data collection, and Sleep Academic Awards (Table 1). Collectively, these initiatives and investigator-initiated research set the foundation for the legacy of scientific advances and funding for sleep and circadian research (Figure 1). Several notable examples of NHLBI-supported science have had a sizable impact on the field, including the pioneering Wisconsin Sleep Cohort study, which revealed the natural history of sleep apnea associated with excessive daytime sleepiness [14, 15], incident hypertension [16–18], cardiomyopathy [15, 19], incident coronary heart disease [18], and carotid artery disease [20]. The landmark Sleep Heart Health Study leveraged multiple NHLBI-supported cohort studies nationwide to assess sleep apnea incidence in a large population and incident stroke [21], arrhythmia [22], diabetes [23], and all-cause mortality [24] during 14 years of follow-up. Other pivotal studies have discovered mechanisms through which mild sleep disturbance, irregular sleep, and untreated sleep disorders is associated with vascular endothelial inflammation [25] and may contribute to the future risk of hypertension, especially during gestation [26]. The NIH Sleep Disorders Research Plan in 2003 [27] guided a second phase of initiatives to stimulate clinical sleep research translation including pediatric sleep disorders, cardiometabolic disease, and HIV outcomes. Multisite clinical trials evaluated the treatment of sleep apnea in children and adults. NHLBI support for genetic epidemiology studies led to the discovery of risk factors for sleep apnea [28–30] and gene variants associated with racial and ethnic differences in sleep apnea risk [31–33]. These genetic discoveries served as an impetus for objective overnight assessment of breathing in the 15 000-participant NHLBI-led Hispanic Community Health Study [34]. More recently, establishment of the National Sleep Research Resource (https://sleepdata.org/) is contributing big data resources and opportunities needed to improve the clinical evaluation of breathing and integrate polysomnographic sleep data with trans-omic findings for large-scale analyses.

Table 1.

Selected NCSDR Research Programs

Title	Years
Sleep Heart Health Study	1995–2008
Sleep Academic Award	1996–2002
Molecular Biology and Genetics of Sleep and Sleep Disorders	1997–2001
Obstructive Sleep Apnea in Children	1998–2002
Specialized Centers: Neurobiology of Sleep and Sleep Apnea	1999–2009
Phenotypic Characterization of Sleep in Mice	1999–2003
Nocturnal Asthma, Chronobiology, and Sleep	1999–2004
Interrelationship of Sleep and Heart, Lung, and Blood Diseases	2002–2007
Sleep and Sleep Disorders in Children	2003–2007
Inter-relationship of Sleep, Fatigue, and HIV/AIDS	2004–2009
Sleep and Sleep Disorders in Metabolic Syndrome	2005–2009
Obesity and Sleep Duration	2006–2011
Circadian-Coupled Cellular Function in Heart, Lung, and Blood Tissue	2009–2012
Reducing Cardiovascular Disease Risk Through Treatment of Obstructive Sleep Apnea	2010–2013
Education Research in Sleep Health and Sleep-Circadian Biology	2012–2014
Mechanisms and Consequences of Sleep Disparities	2017–2023
Circadian Mechanisms Contributing to Obesity, Diabetes Metabolism, and Underlying Heart, Lung, and Blood Disorders	2017–2021

Figure 1.

Estimated NIH funding for sleep research each fiscal year from 1996 to 2017. Funding estimate includes the total of direct and indirect costs. Estimates from 1996 to 2006 are based on the annual report of the Trans NIH Sleep Research Coordinating Committee. Estimates from 2007 to 2017 are based on the NIH-wide budget category “Sleep Disorders Research” [13]. Total costs in this figure are lower in 2015 (by $71 million), 2016 (by $45 million), and 2017 (by $22 million) compared to published NIH sleep research budget category data to adjust for contracts unrelated to sleep and circadian research.

In the 2011 Sleep Research Plan, NIH Director Dr. Francis S. Collins recognized the current phase of NCSDR operations as exemplifying the NIH goal of fostering fundamental creative discoveries and innovation, and applying that knowledge to ultimately protect health and prevent disease [35]. New basic science initiatives have facilitated a spectrum of advances in understanding circadian-coupled cellular function, ranging from the organization of gene expression [36] to energy metabolism [37], mitochondrial redox [38], immune defense [39], inflammation [40], and autophagy. Circadian triggered pathophysiology in animal models includes vascular dysfunction [41, 42], cardiac arrhythmia [43], ischemic injury [44], lung remodeling, pancreatic beta cell dysfunction [45], and neurodegeneration [46]. Studies now underway are investigating how insufficient sleep and sleep disorders are coupled to microvascular and neurobiological mechanisms underlying cognitive decline. Multisite clinical trials were launched to determine if treating adult obstructive sleep apnea reduces cardiovascular disease risks and whether surgical treatment improves sleep disordered breathing during childhood. A new clinical study program is now underway to investigate potentially life-threatening prematurity-related abnormalities in newborn ventilation [47].

Greater NIH-wide coordination is accelerating the pace of population-based research discoveries. Collection of sleep data in a National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) project has determined the prevalence of untreated sleep apnea in obese diabetics [48], and whether untreated sleep apnea complicates medical management of type 2 diabetes [49]. The incorporation of sleep measures to NICHD programs has revealed that sleep deficiency and sleep apnea increases gestational cardiometabolic disease risk [50]. A treatment trial jointly sponsored by NHLBI and NICHD is now underway to determine whether apnea treatment during pregnancy reduces cardiometabolic risks [51].

Looking Toward the Future

As we look back over the evolution of the NCSDR, there have been great advances in education, coordination, and breakthroughs in sleep and sleep disorders research. In a little more than two decades, the field has advanced from basic knowledge of how sleep/somnolence affects safety, to understanding sleep disorders (such as narcolepsy and sleep apnea), and the broad multisystem effects of sleep and sleep deprivation on health.

The power of sleep and circadian scientific accomplishments, such as the 2017 Nobel Prize in Physiology or Medicine for discoveries of molecular mechanisms controlling circadian rhythm [52] exemplifies how the combination of basic science and medicine can overcome barriers to promote the health and well-being of society. A growing community partnership with researchers and public stakeholders, the Sleep Disorders Research Advisory Board, NIH components, and other Federal agencies is contributing to the development of a future research agenda recognizing sleep and circadian health and function as a fundamental principle of biological organization. Sleep and circadian mediated alignment of diverse metabolic, immunologic, and behavioral systems contributes to mechanisms of adaptation, disease tolerance, and resilience. Juxtaposing molecular advances in understanding sleep and circadian coupled functions with knowledge of disease processes, disease states, and aging is opening new avenues for research to improve medical therapies.

The future vision is founded on developing sustainable research strategies that will deliver scientific advances and the sound evidence needed by medicine, health care systems, and governmental human services to promote public health, well-being, and safety. Quantitative biomarker tools are needed to study how individual differences in lifestyle, environment, and biology contribute to sleep and circadian abnormalities, and to enable advances in prevention and treatment that support health, performance, and safety across the lifespan. Multidisciplinary teams will leverage a new generation of circadian-sensitive biomarker tools and knowledge to determine how abnormalities in circadian-ordered gene expression contribute to inflammation, oxidative stress, and other disease processes. Elucidating mechanistic sleep and circadian connections that affect disease open new avenues to advance both personalized medicine and population health surveillance.

Sleep deficiency because of insufficient sleep, irregular sleep schedules, and poor-quality sleep or sleep disorders is pervasive across the United States. Mechanistic studies are needed to understand how poor sleep and environmental exposures influence circadian-coupled biology, protein misfolding, and epigenetic pathobiology. Clinical studies are needed to demonstrate how protecting sleep and circadian health would reduce real-world disease risks and to open new avenues for the development of improved pharmacotherapies. Gene-based individual variation in the duration of circadian cycles (tau) exist at a cellular level, but the significance to disease is not well understood. A myriad of high value scientific opportunities are within reach building on two decades of sleep and circadian biology discoveries.

Great progress has been made establishing and advancing sleep research, education, and coordination of programs in keeping with the original legislation. A growing community of researchers and infrastructure will foster the pursuit of next step discoveries linking sleep and circadian biology to health, disease, and public safety. NCSDR will continue to represent the field and bolster the spectrum of scientific opportunities and innovation serving public health. We look forward to continuing our remarkable partnership to improve sleep health for all.

Conflict of interest statement. None declared.