There’s tiredness and fatigue, difficulty concentrating, perhaps irritability or even tired giggles.
Far fewer people have experienced the effects of prolonged sleep deprivation, including disorientation, paranoia and hallucinations.
Total, prolonged sleep deprivation, however, can be fatal. While it has been reported in humans only anecdotally, a widely cited study in rats conducted by Chicago-based researchers in 1983 showed that a total lack of sleep inevitably leads to death.
Yet, despite decades of study, a central question has remained unsolved: why do animals die when they don’t sleep?
Now, Harvard Medical School neuroscientists have identified an unexpected, causal link between sleep deprivation and premature death.
In a study on sleep-deprived fruit flies, researchers found that death is always preceded by the accumulation of molecules known as reactive oxidative species (ROS) in the gut.
When fruit flies were given antioxidant compounds that neutralize and clear ROS from the gut, sleep-deprived flies remained active and had normal lifespans. Additional experiments in mice confirmed that ROS accumulate in the gut when sleep is insufficient.
The findings, published in Cell on June 4, suggest the possibility that animals can indeed survive without sleep under certain circumstances. The results open new avenues of study to understand the full consequences of insufficient sleep and may someday inform the design of approaches to counteract its detrimental effects in humans, the authors said.
“We took an unbiased approach and searched throughout the body for indicators of damage from sleep deprivation.
We were surprised to find it was the gut that plays a key role in causing death,”
said senior study author Dragana Rogulja, assistant professor of neurobiology in the Blavatnik Institute at HMS.
“Even more surprising, we found that premature death could be prevented. Each morning, we would all gather around to look at the flies, with disbelief to be honest. What we saw is that every time we could neutralize ROS in the gut, we could rescue the flies,” Rogulja said.
Scientists have long studied sleep, a phenomenon that appears to be fundamental for life, yet one that in many ways remains mysterious. Almost every known animal sleeps or exhibits some form of sleeplike behavior.
Without enough of it, serious consequences ensue. In humans, chronic insufficient sleep is associated with heart disease, type 2 diabetes, cancer, obesity, depression and many other conditions.
Previous research has shown that prolonged, total sleep restriction can lead to premature death in animal models. In attempts to answer how sleep deprivation culminates in death, most research efforts have focused on the brain, where sleep originates, but none have yielded conclusive results.
Spearheaded by study co-first authors Alexandra Vaccaro and Yosef Kaplan Dor, both research fellows in neurobiology at HMS, the team carried out a series of experiments in fruit flies, which share many sleep-regulating genes with humans, to search for signs of damage caused by sleep deprivation throughout the body.
To monitor sleep, the researchers used infrared beams to constantly track the movement of flies housed in individual tubes.
They found that flies can sleep through physical shaking, so the team turned to more sophisticated methods. They genetically manipulated fruit flies to express a heat-sensitive protein in specific neurons, the activity of which are known to suppress sleep.
When flies were housed at 29 degrees C (84 degrees F), the protein induced neurons to remain constantly active, thus preventing the flies from sleeping.
After 10 days of temperature-induced sleep deprivation, mortality spiked among the fruit flies and all died by around day 20. Control flies that had normal sleep lived up to approximately 40 days in the same environmental conditions.
Because mortality increased around day 10, the researchers looked for markers of cell damage on that and preceding days. Most tissues, including in the brain, were indistinguishable between sleep-deprived and non-deprived flies, with one notable exception.
The guts of sleep-deprived flies had a dramatic buildup of ROS–highly reactive, oxygen-containing molecules that in large amounts can damage DNA and other components within cells, leading to cell death.
.The accumulation of ROS peaked around day 10 of sleep deprivation, and when deprivation was stopped, ROS levels decreased.
Additional experiments confirmed that ROS builds up in the gut of only those animals that experienced sustained sleep loss, and that the gut is indeed the main source of this apparently lethal ROS.
“We found that sleep-deprived flies were dying at the same pace, every time, and when we looked at markers of cell damage and death, the one tissue that really stood out was the gut,” Vaccaro said. “I remember when we did the first experiment, you could immediately tell under the microscope that there was a striking difference. That almost never happens in lab research.”
The team also examined whether ROS accumulation occurs in other species by using gentle, continuous mechanical stimulation to keep mice awake for up to five days. Compared to control animals, sleep-deprived mice had elevated ROS levels in the small and large intestines but not in other organs, a finding consistent with the observations in flies.
To find out if ROS in the gut play a causal role in sleep deprivation-induced death, the researchers looked at whether preventing ROS accumulation could prolong survival.
They tested dozens of compounds with antioxidant properties known to neutralize ROS and identified 11 that, when given as a food supplement, allowed sleep-deprived flies to have a normal or near-normal lifespan.
These compounds, such as melatonin, lipoic acid and NAD, were particularly effective at clearing ROS from the gut. Notably, supplementation did not extend the lifespan of non-deprived flies.
The role of ROS removal in preventing death was further confirmed by experiments in which flies were genetically manipulated to overproduce antioxidant enzymes in their guts. These flies had normal to near-normal lifespans when sleep-deprived, which was not the case for control flies that overproduced antioxidant enzymes in the nervous system.
The results demonstrate that ROS buildup in the gut plays a central role in causing premature death from sleep deprivation, the researchers said, but cautioned that many questions remain unanswered.
“We still don’t know why sleep loss causes ROS accumulation in the gut, and why this is lethal,” said Kaplan Dor. “Sleep deprivation could directly affect the gut, but the trigger may also originate in the brain.
Similarly, death could be due to damage in the gut or because high levels of ROS have systemic effects, or some combination of these.”
Insufficient sleep is known to interfere with the body’s hunger signaling pathways, so the team also measured fruit fly food intake to analyze whether there were potential associations between feeding and death.
They found that some sleep-deprived flies ate more throughout the day compared with non-deprived controls. However, restricting access to food had no effect on survival, suggesting that factors beyond food intake are involved.
The researchers are now working to identify the biological pathways that lead to ROS accumulation in the gut and subsequent physiological disruptions.
The team hopes that their work will inform the development of approaches or therapies to offset some of the negative consequences of sleep deprivation. One in three American adults gets less than the recommended seven hours of sleep per night, according to the U.S. Centers for Disease Control and Prevention, and insufficient sleep is a normal part of life for many around the world.
“So many of us are chronically sleep deprived. Even if we know staying up late every night is bad, we still do it,” Rogulja said. “We believe we’ve identified a central issue that, when eliminated, allows for survival without sleep, at least in fruit flies.”
“We need to understand the biology of how sleep deprivation damages the body, so that we can find ways to prevent this harm,” she said.
Additional authors on the study include Keishi Nambara, Elizabeth Pollina, Cindy Lin and Michael Greenberg.
Funding: The study was supported by the New York Stem Cell Foundation, the Pew Charitable Trusts and the National Institutes of Health (R73 NSO72030). Additional support includes an EMBO long-term fellowship, a Fondation Bettencourt Schueller fellowship, an Edward R. and Anne G. Lefler Center postdoctoral fellowship, an Alice and Joseph E. Brooks Postdoctoral Fellowship and a Life Sciences Research Foundation fellowship.
Sleep Disturbance as a Risk Factor for Cardiovascular Disease
Sleep is a multidimensional biobehavioral process including components such as sleep duration, continuity, architecture, timing, rhythmicity, regularity, and satisfaction (Buysse, 2014).
Individual dimensions of sleep can be measured along a continuum (e.g., hours of sleep), in terms of discrete categories (e.g., short or long sleepers), or described in terms of disorders (e.g., insomnia, sleep apnea). This article will use short sleep duration and insomnia to illustrate opportunities for developing and refining integrative models of the influence of our waking and sleeping lives on the pathophysiology and clinical course of CVD.
Short sleep duration and insomnia are both highly prevalent, strongly linked to cardiovascular risk via common physiological mechanisms, and modifiable via nonpharmacological approaches. Not included in this paper is the well-documented impact of sleep apnea on CVD, which has been systematically reviewed elsewhere (e.g., Dong, Zhang, & Qin, 2013).
The reader interested in the influence of racial/ethnic disparities on sleep apnea and CVD risk, including the importance of sociocultural context and environment, is referred to recent integrative reviews (Grandner et al., 2016a; Williams et al., 2015).
In their 2015 joint consensus statement, the Sleep Research Society (SRS) and American Academy of Sleep Medicine (AASM) recommended that adults regularly obtain 7 hours or more of sleep to promote optimal health and functioning (Watson et al., 2015).
Yet, only 65.2% of adult respondents in the 2014 Behavioral Risk Factor Surveillance System survey reported sleeping 7 or more hours per night (Liu et al., 2014). At the other end of the sleep duration spectrum, discrepant evidence linking long sleep duration to adverse health outcomes led the SRS and AASM to state that the health risk of sleeping 9 hours or more was uncertain (Watson et al., 2015).
Sleep duration may be measured by polysomnography (PSG), which is used to quantify the amount of time spent in rapid-eye-movement (REM) and non-REM sleep. While providing a physiological measure of sleep, the cost and burden associated with PSG can be a barrier to its use.
Population-based studies typically measure sleep duration by self-report or wrist actigraphy, the latter of which estimates sleep duration based on the pattern and level of accelerometer- assessed activity counts.
Behavioral and objective measures of sleep duration, as assessed by wrist actigraphy and PSG, respectively, generally represent the total number of minutes or hours of sleep (typically, nocturnal sleep). Self-reported sleep duration may be measured by retrospective report (e.g., past month) or via daily diaries. While less expensive than PSG and actigraphy, the wording and interpretation of self-report sleep duration questions may differ across studies and participant characteristics may influence responses (Matthews et al., 2018).
The systematic study of sleep and CVD traces its roots back to several reports from the Alameda County Study. Evidence that mortality rates from ischemic heart disease were lowest in men and women who reported habitual sleep durations of 7 to 8 hours inexorably linked sleep duration and cardiovascular health (Wingard, Berkman & Brand, 1982; Wingard & Berkman, 1983).
Numerous epidemiological studies have subsequently reported a U-shaped relationship between sleep duration and cardiovascular morbidity and mortality. For example, cross-sectional analysis of self-reported sleep duration and cardiovascular morbidity in 30,000 National Health Interview Survey participants showed increased odds of any CVD in short and long sleepers (Sabanayagam & Shankar, 2010).
Multivariate odds ratios of 2.20 and 1.57 were observed in those reporting sleep durations of ≤ 5 or ≥ 9 hours, respectively, after adjusting for known sociodemographic, behavioral, and anthropometric CVD risk factors, as well as CVD and psychiatric history. A 2010 meta-analysis of 15 studies conducted in the United States, Europe, and Asia, with over 400,000 participants and follow-up periods between 6.9 – 25 years, reported significant associations among self-reported habitual sleep duration and clinically confirmed cardiovascular outcomes (Cappuccio, Cooper, D’Elia, Strazzullo, & Miller, 2011).
Compared to the reference category of 7 – 8 hours of sleep per night, relative risk for developing or dying from coronary heart disease (CHD) or stroke was between 1.48–1.15 for short sleepers (< 5–6 hours/night) and 1.38–1.65 for long sleepers (>8–9 hours/night).
Reports of increased blood pressure (BP) and arterial stiffness in response to acute sleep deprivation provide experimental support linking short sleep to CVD (Ogawa et al, 2003; Sunbul, Kanar, Durmus, Kivrak, & Sari, 2014).
Experimental sleep restriction, which more closely mimics short sleep duration, has been shown to blunt sleep-associated blood pressure dipping and to reduce endothelial-dependent vasodilation in healthy young adults (Sauvet et al., 2015; Yang, Haack, Gautam, Meier-Ewert, & Mullington, 2017).
In the only study of its kind to date, Haack and colleagues (2013) evaluated the effects of a six-week sleep extension protocol, compared to a maintenance condition, in a group of 22 adults with prehypertension or hypertension type 1. The sleep extension protocol resulted in significant decreases in beat-to-beat systolic and diastolic blood pressure with no comparable decreases in the maintenance condition.
Insomnia is the most common sleep complaint and disorder, with prevalence estimates of 30% for insomnia symptoms and 5 to 10% for insomnia disorder (see Mai & Buysse, 2008). The American Psychiatric Association definition of insomnia further stipulates that these sleep complaints occur at least 3 nights per week for at least 3 months, despite adequate opportunity for sleep, that they cause significant distress or daytime impairment, and are not attributable to the physiological effects of a drug of abuse or medication (American Psychiatric Association, 2013).
Insomnia is diagnosed by clinical interview with a trained clinician and does not require objective findings as measured by PSG. In contrast to insomnia disorder, insomnia symptoms may be assessed by standardized questionnaires such as the Insomnia Severity Index (ISI; Morin, Belleville, Bélanger, & Ivers, 2011), discrete symptoms (e.g., report of difficulty initiating sleep), or actigraphy- or PSG-assessed indices of sleep continuity [e.g., sleep latency (SL), wakefulness after sleep onset (WASO), sleep efficiency (SE; sleep duration/time in bed x 100)].
A 2014 meta-analysis of 17 cohort studies, including 311,260 adult who were free of CVD at baseline, reported significant prospective associations among insomnia (symptoms or disorder) and specific cardiovascular outcomes including myocardial infarction, coronary heart disease, stroke and CVD mortality (Li, Zhang, Hou, & Tang, 2014).
Multivariable analyses demonstrated that insomnia was associated with each outcome, with increased relative risk between 28–55% for incident disease and 33% for cardiovascular mortality, compared to individuals without insomnia. Given that CVD develops over years and decades, other studies have focused on links between insomnia and early disease markers.
For example, a 2013 meta-analysis of 7 studies, including over 40,000 adults, reported significant associations among symptoms of insomnia and incident hypertension during follow-up periods of one or more years (Meng, Zheng, & Hui, 2013). The relative risks (95% confidence intervals [CI]) for difficulties maintaining sleep and early morning awakenings were 1.20 (1.06–1.36) and 1.14 (1.07–1.20) respectively. Evidence of statistical heterogeneity and publication bias was low in both meta-analyses, supporting the strength of study findings.
A handful of studies have evaluated subclinical indices of CVD in patients with insomnia compared to good sleeper control participants. For example, a laboratory-based study of normotensive adults reported elevated heart rate and blunted day-to-night blood pressure dipping in patients compared to control participants (Lanfranchi et al., 2009).
Nakazaki and colleagues (2012) reported that intima-media thickness and carotid plaque scores were significantly elevated in 33 older adults with insomnia disorder compared to 53 good sleeper control participants, after adjusting for other known risk factors.
Insomnia symptoms, which are prevalent in the general population, have also been associated with cardiovascular risk factors. A recent randomized clinical trial in 402 adults with comorbid insomnia and hypertension showed significant improvements in blood pressure control in patients treated with Estazolam compared to placebo, with BP compliance rates (<140/90 mmHg) over a 28-day period of 74.5% in the treatment group and 50.5% in the placebo group (Li et al., 2017)
Multidimensional Sleep Disturbances
For the most part, evidence linking sleep to cardiovascular morbidity and mortality is based on individual dimensions of sleep. Yet, individual dimensions of sleep are not experienced in isolation. In one of the most important discoveries in sleep medicine in the past decade, Vgontzas and colleagues identified a subgroup of patients with insomnia at elevated risk for decrements in health and functioning.
The defining characteristic of this high-risk phenotype is the combined presentation of chronic insomnia and objectively-assessed short sleep duration (< 6 hours). Their first study reported that adults with the insomnia+objective short sleep phenotype were more likely to present with hypertension, compared to patients with insomnia who slept 6 or more hours in the lab as well as individuals who slept less than 6 hours without insomnia (Vgontzas, Liao, Bixler, Chrousos, & Vela-Bueno 2009a).
A prospective study in the same cohort later demonstrated that individuals with the high-risk phenotype had a nearly 4-fold increased odds of developing incident hypertension over a 7.5-year follow-up period (Fernandez-Mendoza et al., 2012). Both cross-sectional and prospective effects were robust to adjustment for standard CVD risk factors as well as objectively-assessed sleep disordered breathing.
More recently, Bathgate and colleagues (2016) replicated these findings in a study of 255 adults with insomnia studied at two large university health centers. After adjusting for standard CVD risk factors, the increased risk of reporting hypertension in the insomnia+objective short sleep group was 3.59 (95% CI, 1.58, 8.17), compared to individuals with insomnia who slept 6 or more hours.
Extending this work to self-report measures, several large European cohort studies have reported increased risk for registry-based clinical cardiovascular outcomes in individuals characterized by self-reported short sleep duration in combination with subjectively-assessed sleep quality complaints (e.g., Hoevenaar-Blom, Spijkerman, Kromhout, van den Berg, & Verschuren, 2011; Rod et al., 2014).
Physiological Mechanisms Linking Disturbed Sleep to Cardiovascular Disease
Sleep duration and insomnia are known to influence the pathophysiology of CVD via inflammatory, autonomic, and metabolic pathways, among others. These physiological mechanisms are used to illustrate links between sleep and CVD; each may, similarly, inform multidimensional, integrative models of the influence of our waking and sleeping lives on the pathophysiology and clinical course of CVD.
Inflammation plays an important role in the development and progression of CVD (e.g., Willeit et al., 2016). A recent systematic review of 72 studies including more than 50,000 participants concluded that short sleep duration was a significant correlate of increased circulating interleukin-6 (IL-6) levels and long sleep duration was associated with elevated levels of both IL-6 and C-reactive protein (CRP; Irwin, Olmstead, & Carroll, 2016).
Elevated CRP levels have also been linked to self-reported and actigraphy-assessed short sleep duration (Grandner et al., 2013; Hall, Lee, & Matthews, 2015a). In the same meta-analysis, laboratory- based sleep deprivation was not associated with increased inflammation, perhaps due to the time course of inflammatory processes.
While experimental sleep restriction is associated with acute increases in the activity of upstream pro-inflammatory molecular pathways (e.g., Tumor Necrosis Factor-α (TNFα) messenger RNA and nuclear factor (NF)-κβ activation), downstream effects on circulating levels of IL-6, CRP and TNFα may not be observed during the short follow-up periods employed in experimental sleep restriction/deprivation studies (Irwin et al., 2016).
Indeed, a protocol designed to mimic habitual sleep restriction in healthy young adults reported significant increases in circulating proinflammatory cytokines following a week-long restriction from 8 to 6 hours of sleep (Vgontzas et al., 2004).
Inflammation has, similarly, been linked to insomnia disorder. For example, two small studies reported increased nocturnal IL-6 in patients with chronic insomnia relative to good sleeper control participants (Burgos et al., 2006; Vgontzas et al., 2002).
Evidence from a randomized controlled trial (n=123) of the comparative efficacy of a multi-component cognitive behavioral therapy for insomnia (CBTI), Tai Chi Chih (TCC), and an attention-control sleep seminar (SS) suggests that insomnia may play a causal role in inflammation.
Compared to the SS control condition, CBTI was associated with decreased indices of cellular and systemic inflammation and TCC was associated with decreased cellular inflammation only; however, both active interventions were associated with decreased activity of proinflammatory transcriptional profiles (e.g., reduced NF-κβ activity) (Irwin et al., 2014; Irwin et al., 2015).
The multicomponent nature of the CBTI condition, which was modified to include behavioral strategies to enhance mood and daytime activity levels, precludes attributions about the mechanisms linking modified CBTI to inflammation, including differences in inflammation profiles over the follow-up period in both active treatment groups (see Irwin et al., 2014). What we do know is that effective treatment of insomnia was associated with significant decreases in inflammation, irrespective of treatment group allocation.
At follow-up, CRP levels were significantly lower in participants whose insomnia remitted, compared to those who still met diagnostic criteria for insomnia (Irwin et al., 2014). In contrast to insomnia disorder, two population-based studies reported that self-reported symptoms of insomnia were not associated with inflammation, measured by CRP, IL-6, or TNF-α, after multivariate adjustment (Laugsand, Vatten, Bjorngaard, Hveem, & Janszky, 2012; Prather, Vogelzangs, & Pennix, 2015).
Autonomic Nervous System Activity
Autonomic nervous system (ANS) activity in the form of decreased parasympathetic activity and increased sympathetic activity is a recognized risk factor for CVD (see Hillebrand et al., 2013). Consistent with the hypothesis that short sleep duration increases CVD risk though autonomic dysfunction, experimental sleep deprivation has been shown to decrease parasympathetic activity and increase sympathetic activity, indexed by high-frequency heart rate variability (HF-HRV) and plasma norepinephrine (NE), respectively (Zhong et al., 2005). Naturalistic observation of on-call physicians, deprived of sleep for 26 hours, revealed diminished HF-HRV and high levels of plasma NE and epinephrine (Tobaldini et al., 2013).
Insomnia has long been described as a disorder characterized by cognitive and somatic hyperarousal (see Bonnet & Arand, 2010). Indeed, early case control studies suggested that parasympathetic activity was significantly lower in patients with insomnia compared to age- and sex-matched participants without insomnia (see Bonnet & Arand, 2010). Yet, as reviewed by Dodds and colleagues (2017), the results of subsequent studies have been highly mixed, perhaps due to the diversity of approaches across studies including differences in diagnostic criteria, sample characteristics, methods and measurement of ANS activity, etc. Converging evidence does suggest ANS dysregulation in patients with the insomnia+objective short sleep phenotype (see Fernandez-Mendoza, 2017).
Chronic metabolic dysfunction in the form of insulin resistance and impaired glucose tolerance is a leading risk factor for CVD morbidity and mortality (e.g., Huang et al., 2014). A seminal study published in 1999 demonstrated that restricting sleep to 4 hours per night over 6 consecutive nights profoundly reduced glucose clearance and insulin response to glucose in a sample of 11 young, lean males to levels usually observed in geriatric patient populations (Spiegel, Leproult, & Van Cauter, 1999).
Subsequent experimental and observational studies have continued to replicate and extend these findings, suggesting that sleep curtailment is a critical risk factor for the development of obesity, diabetes, and their downstream effects on cardiovascular health (Van Cauter, Spiegel, Tasali, & Leproult, 2008).
Two recent studies in healthy adults with lifestyle-restricted short sleep reported improvements in insulin sensitivity following short-term protocols that extended sleep by approximately one hour per night (Killick et al., 2015; Leproult, Deliens, Gilson, & Peigneux, 2015).
A similar pattern of metabolic dysfunction is seen in insomnia in most, but not all, studies (see Depner, Stothard, & Wright, 2014). Vgontzas and colleagues (2009b) reported that diabetes risk was nearly three times greater in patients with insomnia and laboratory-assessed sleep durations of < 5 hours, compared to adults without insomnia and sleep durations of 6 or more hours of sleep, after adjusting for standard diabetes risk factors as well as symptoms of depression and sleep apnea.
A meta-analysis of 6 prospective studies including over 15,000 adults evaluated type 2 diabetes incidence in relation to self-reported symptoms of insomnia (Cappuccio, D’Elia, Strazzullo, & Miller, 2010). Results indicated an increased risk of incident diabetes over a 3- to 32-year follow up in association with symptoms of difficulty initiating [RR = 1.28 (95% CI 1.03–1.60)] and maintaining sleep [RR = 1.48, (95% CI 1.13–1.96)]. The authors further noted that associations among symptoms of insomnia and incident diabetes risk were not attenuated when analyses were restricted to studies with direct clinical assessments (n = 4).
Sleep and Indices of Psychosocial Risk and Resilience
The past 20 years has seen a dramatic increase in the number of studies focused on the psychosocial correlates of sleep. Much of this research has been focused on the impact of psychosocial factors on sleep.
As reviewed below, depression, psychological stress, and close interpersonal relationships have each been linked to sleep duration and insomnia. Yet, the observational and/or cross-sectional nature of many of these studies suggests that attributions of causality are premature.
Importantly, each of these psychosocial factors influences CVD risk (i.e., depression, psychological stress) or resilience (close interpersonal relationships). Also reviewed is the influence of race/ethnicity on sleep duration and insomnia, including its importance to our understanding of disturbed sleep as a risk factor for cardiovascular morbidity and mortality.
A clearer understanding of the extent to which these psychosocial factors influence and are influenced by sleep across racial/ethnic groups is critical to advancing our understanding of the influence of our waking and sleeping lives on the pathophysiology and clinical course of CVD.
As reflected in the diagnostic criteria for major depressive disorder (MDD), depression and disturbed sleep are highly comorbid (American Psychiatric Association, 2013). Prospective observational and experimental studies suggest that insomnia contributes to the onset and clinical course of MDD.
For example, a prospective population-based study of 4,547 Swiss adults found that 17% to 50% of participants with insomnia symptoms lasting 2 weeks or longer subsequently developed incident depression (Buysse et al., 2008). A small RCT that evaluated the impact of antidepressant medication (escitalopram; EsCIT) alone or in combination with CBTI (EsCIT+CBTI) reported higher remission rates of depression and insomnia in the EsCIT+CBTI condition compared to the EsCIT condition (Manber et al., 2008).
These data suggest that treatment related remission of insomnia symptoms may have contributed to the remission of depression. With respect to depression and sleep duration, a meta-analysis of 7 prospective studies including 25,272 participants reported that short [RR=131 (95% CI 1.04–1.64)] and long [RR=1.42 (95% CI 1.04–1.92)] sleep duration were both associated with incident depression, despite heterogeneity in the assessment of depression assessment (self-report rating scales or clinical diagnostic interview) and sleep duration categories (referent group was generally between 6–8 hours) (Zhai, Zhang, & Zhang, 2015). Importantly, results were robust to adjustment for major confounding factors including sociodemographics and body mass index.
Psychological stress is antithetical to sleep. The stress response involves psychophysiological preparation to fight or flee from perceived threat, whereas mental and physiological quiescence are necessary to the initiation of and maintenance of sleep.
A large body of evidence has documented cross-sectional and prospective associations among stress and sleep. For example, disturbed sleep has been associated with numerous indices of psychological stress including academic stress, stressful life events, job and financial strain, lower socioeconomic status, poverty, discrimination, and unfair treatment, among others (e.g., Brindle et al., 2018; Hall et al., 2015b; Patel, Grandner, Xie, Branas, & Gootneratne, 2010).
Objectively- assessed difficulty maintaining sleep, as measured by wakefulness after sleep onset, is the dimension of sleep most reliably associated with stress in cross-sectional and prospective studies (Hall, et al., 2015b; Kim & Dimsdale, 2007).
Moreover, prospective studies suggest that individual differences in vulnerability to stress-related sleep disturbances precipitate and maintain insomnia (Drake, Pillai, & Roth, 2014; Jarrin, Chen, Ivers, & Morin, 2014). Although stress is not consistently associated with sleep duration in observational studies, experimental sleep deprivation has been shown to modulate physiological (e.g., BP, heart rate, cortisol) responses to acute laboratory stress (Franzen et al., 2011; Minkel et al., 2014) and lower the threshold for reporting events as stressful (Minkel et al., 2012).
In their ideal form, interpersonal relationships confer a sense of safety, security, and connection. These feelings, in turn, are important to one’s ability to obtain, fall, and stay asleep which, after all, involves a state of reduced vigilance to one’s surroundings.
Numerous studies have now documented significant cross-sectional associations among greater relationship quality, for both married and nonmarried couples, and fewer objectively- and subjectively-assessed symptoms of insomnia (e.g., Robles, Slatcher, Trombello, & McGinn, 2014; Troxel, Buysse, Hall, & Matthews, 2009).
The concordance between couples’ sleep and the quality of their interactions appears bidirectionally linked such that greater sleep concordance is associated with more positive partner interactions, including conflict resolution, and vice versa (Gordon & Chen, 2014; Hasler & Troxel, 2010). Parent-child relationships are, similarly, important.
A recent study of adolescents reported that close maternal-adolescent relationships buffered the effects of academic stress on self-reported sleep duration and symptoms of insomnia (Van Schalkwijk, Blessinga, & Willemen, Van Der Werf, & Schuengel, 2015). This work, further, suggests that associations between interpersonal relationship quality and sleep may differ for men and women (Hasler & Troxel, 2010; Van Schalkwijk et al., 2015).
Studies conducted in the United States suggest that sleep differs markedly as a function of self-identified racial/ethnic group. To date, the majority of studies have evaluated sleep in blacks (term refers to individuals who self-identify as African-American or black) compared to whites (term refers to individuals who self-identify non-Hispanic Whites or of European descent), as summarized in a meta-analysis of 14 studies, including 1,010 blacks and 3,156 whites, age 18 or older, without diagnosed or suspected sleep disorders (Ruiter, DeCoster, Jacobs, & Lichstein, 2011).
Objectively-assessed sleep duration and sleep efficiency were lower in blacks, with mean effect sizes of −.48 and −.54, respectively. Race/ethnicity differences in subjectively-assessed sleep duration were small (−.23). In another study, genetic ancestry was unrelated to objectively-assessed sleep duration and efficiency (Halder et al., 2017).
Decrements in sleep duration and reports of difficulty initiating sleep have also been observed in other racial/ethnic minorities including Latinos, Chinese- and Asian-Americans, and African and Caribbean immigrants (Chen et al., 2015; Egan, Knutson, Pereira, & von Schantz, 2017).
Multiple modifiable factors contribute to observed racial/ethnic differences in sleep duration and insomnia symptoms. As summarized by others, expectations, attitudes, norms, and beliefs about sleep may influence the interpretation of and response to questionnaires or interviews (Adenekan et al., 2013; Williams et al, 2015).
Other modifiable sociocultural factors that may contribute to decrements in sleep in racial/ethnic minorities include disparities in socioeconomic status (SES), access to health care, characteristics of the physical environment (e.g., crowding, noise, risk to safety), perceived racism and discrimination (see Grandner, Williams, Knutson, Roberts & Jean-Louis, 2016b).
Moderation analyses in the meta-analysis of sleep in blacks and whites by Ruiter and colleagues (2011), similarly, suggest that modifiable risk factors contribute to decrements in sleep duration and, to a lesser extent, sleep efficiency. Setting and employment status had more modest, non-significant, effects on race/ethnicity differences in objectively-assessed sleep efficiency.
While not causal, these data suggest that systemic differences that contribute to racial/ethnic disparities in socioeconomic status and health may, similarly, contribute to decrements in sleep in racial/ethnic minorities in the US. That these factors are modifiable suggests that decrements in sleep duration and efficiency in racial/ethnic minorities, including their long-term impact on cardiovascular morbidity and mortality, are amendable to intervention (Egan et al., 2017).