Goal 1: Elucidate the Sleep and Circadian Mechanisms Underlying Health and Disease
National surveillance data from the Center for Disease Control and Prevention estimates that more than 30% of U.S. adults and more than 65-80% of teens nationwide report sleep deficiency (e.g., insufficient sleep, irregular timing of sleep, poor quality of sleep). Chronic diseases and social determinants of health (e.g., race and ethnicity, housing and the built environment, lifestyle and occupational factors, psychosocial stressors) are all associated with sleep deficiency and circadian misalignment – the mistiming of internal biological cycles relative to external environmental or behavioral factors. Identifying mechanisms underlying sleep and circadian biology is essential for predicting responses to influences that might disrupt regulation of these systems and ultimately lead to early detection of health-to-disease transitions. These mechanistic insights could enable earlier and more precisely targeted interventions that could leverage methodological and technological advances in optogenetics, functional brain imaging, wearable devices, and informatics. Ultimately such refined interventions could be implemented at a population level.
This research would:
- Better define the biological processes involved in maintaining sleep and circadian health to enable early detection of their disruption and the consequent transition to disease.
- Promote health and resilience against disease by leveraging these processes.
High-Priority Research Areas
Basic Mechanistic Studies
- Identify non-neuronal cellular and molecular mechanisms, and inter-organ alignment and crosstalk underlying sleep and circadian biological processes.
- Identify the complex interactions of circadian rhythms across various organ systems through computational and mathematical modeling (systems biology) and identify emergent phenomena that influence health and disease.
- Explore mechanisms underlying the bidirectional relationship of the aging process and circadian rhythms.
- Advance mechanistic understanding of the pathways modulating pain, reward, sleep, and circadian rhythms to identify new therapies.
Identification of Disease Processes and Biomarkers
- Identify sleep and circadian influences on the biology underlying obesity and cardiometabolic risk in humans and develop preclinical models to better tailor interventions in clinical-translational studies.
- Understand the interplay between intermittent hypoxia, sympathetic activation, the microbiome, and endogenous stem/progenitor cells, and how this interplay contributes to disease progression.
- Develop and test preclinical models of sleep and circadian disturbances in relation to critical illness (e.g., sepsis) and identify novel targets for drug discovery and therapeutic management.
- Explore single-cell analytics to understand the cellular phenomena of sleep and circadian rhythms and enable discovery of surrogate biomarkers for sleep and circadian disorders.
Pathogenic Effects of Sleep and Circadian Disruption
- Determine the brain mechanisms and effects of sleep and circadian rhythms on development, illness course, and treatment of mental health disorders, and identify the genetic basis of such interactions.
- Explore the mechanistic basis for circadian rhythm and/or sleep disruption and cancer risk.
- Identify the effects of sleep disruption on reproductive development and function.
- Explore the role of sleep and circadian rhythms in blood brain barrier regulation as it affects drug efficacy.
- Explore the genetic, epigenetic, molecular, cellular, and systemic mechanisms that determine sex-related differences in sleep and circadian disorders.
- Define the sex-related differences in sleep quality and quantity in relationship to autoimmune disease.
- Identify the neural mechanisms and bidirectional interactions between sleep deprivation or disruption, and mental health disorders, including emotional dysregulation and mood disorders.
Long Term Environmental and Population Effects
- Understand the effects of developmental alcohol exposure on sleep patterns later in life, and the mechanisms of alcohol-related sleep disorders.
- Examine mechanisms underlying sleep-related pathology contributing to risk for Alcohol Use Disorder (AUD) and the role of persistent sleep problems emerging during abstinence from alcohol use in relapse.
- Elucidate multilevel and multifactorial causal pathways for disparities in sleep and circadian disorders. For example, examine the role of sociocultural and physical/built environmental determinants on population sleep disparities.
- Explore the effects of environmental exposures (e.g., particulates, pathogens, temperature, light exposure, humidity) on sleep and circadian rhythms, and downstream consequences on health, such as for poor diet, physical inactivity, sedentary behaviors, organ dysfunction and disease.
- Explore the effects of substance use such as alcohol, cigarettes, and illicit drugs (e.g., methamphetamine, cocaine, heroin, fentanyl) and misuse of psychotherapeutic drugs (e.g., prescription opioids and stimulants) and how disrupted sleep contributes to addiction.
NIH Sleep Research Plan Strategic Goals
Goal 1: Sleep and Circadian Mechanisms Underlying Health and Disease