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2018

Grandner M, Mullington J, Hashmi S, Redeker N, Watson N, Morgenthaler T. Sleep Duration and Hypertension: Analysis of > 700,000 Adults by Age and Sex. J Clin Sleep Med. 2018;14(6):1031–1039. doi:10.5664/jcsm.7176
STUDY OBJECTIVES: The objective of this study was to evaluate the cross-sectional relationship between sleep duration and hypertension in a large, nationally-representative dataset that spans 10 years. This analysis may provide detailed information with high resolution about how sleep duration is related to hypertension and how this differs by demographic group. METHODS: Data were aggregated from the 2013 Behavioral Risk Factor Surveillance System (n = 433,386) and the combined 2007-2016 National Health Interview Surveys (n = 295,331). These data were collected by the Centers for Disease Control and Prevention from nationally-representative samples. Surveys were combined, and survey-specific weights were used in all analyses. Sleep duration was assessed with the item, "On average, how many hours of sleep do you get in a 24-hour period?" in both surveys. Hypertension was assessed as self-reported history. Covariates were assessed identically in both datasets and included, age (in 5-year groupings), sex, race/ethnicity, and employment status. RESULTS: In adjusted analyses, compared to 7 hours, increased risk of hypertension was seen among those sleeping ≤ 4 hours (odds ratio [OR] = 1.86, .0005), 5 hours (OR = 1.56, .0005), 6 hours (OR = 1.27, .0005), 9 hours (OR = 1.19, .0005), and ≥ 10 hours (OR = 1.41, .0005). When stratified by age, sex, and race/ethnicity groups, short sleep was associated with increased risk for all age groups 70 years, and long sleep (≥ 10 hours only) was associated with risk for all except 24 years and > 74 years. Findings for short sleep were relatively consistent across all race/ethnicities, although findings for long sleep were less pronounced among Black/African-American and Other/Multiracial groups. A significant sleep by 3-way sleep × age × sex interaction ( .0005) suggests that the relationship depends on both age and sex. For both men and women, the OR of having hypertension associated with short sleep decreases with increasing age, but there is a higher association between short sleep and hypertension for women, throughout the adult lifespan. CONCLUSIONS: Both short and long sleep duration are associated with increased hypertension risk across most age groups. The influence of covariates is stronger upon long sleep relationships. Relationships with short sleep were stronger among younger adults and women.
Alkozei A, Killgore WD, Smith R, Dailey N, Bajaj S, Raikes A, Haack M. Chronic sleep restriction differentially affects implicit biases toward food among men and women: preliminary evidence. J Sleep Res. 2018;27(4):e12629. doi:10.1111/jsr.12629
Chronic sleep restriction and obesity are two major public health concerns. This study investigated how chronic sleep restriction changes implicit attitudes towards low- and high-calorie foods. In a randomized, counterbalanced cross-over design, 17 participants (eight females, nine males) underwent two laboratory testing sessions where they were either sleep-restricted for 3 weeks (i.e. underwent three weekly cycles of 5 nights of 4 h of sleep followed by 2 nights of 8 h of sleep opportunity) or received 3 weeks of control sleep (i.e. 8 h of sleep opportunity per night for 3 weeks). There was evidence for a significant sleep condition x sex interaction (F  = 4.60, P = 0.04). After chronic sleep restriction, men showed a trend towards a significant decrease in their implicit attitudes favouring low-calorie foods (P = 0.08), whereas women did not show a significant change (P = 0.16). Men may be at increased risk of weight gain when sleep-deprived due to a reduced bias towards low-calorie foods.
Alkozei A, Haack M, Skalamera J, Smith R, Satterfield B, Raikes A, Killgore WD. Chronic sleep restriction affects the association between implicit bias and explicit social decision making. Sleep Health. 2018;4(5):456–462. doi:10.1016/j.sleh.2018.07.003
OBJECTIVES: Previous work suggests that sleep restriction (SR) reduces cognitive control and may increase negative implicit biases. Here we investigated whether SR might influence decision making on a social-evaluative task where individuals had to make judgments of threat based on facial photographs. Furthermore, we investigated the effect of changes in negative implicit biases as a result of sleep restriction on this decision-making task. DESIGN: Fourteen healthy adults underwent two 3-week counterbalanced in-laboratory stays (chronic SR and control sleep [CS] conditions). Participants completed the Arab Muslim Names implicit association test (a measure of implicit bias/attitudes toward Arab Muslims) and the Karolinska Airport Task (a measure of explicit decision making). The Karolinska Airport Task requires participants to judge the potential dangerousness of individuals based on facial photographs. RESULTS: After SR, participants were more likely to deem individuals with less positive and more negative facial features as dangerous than after CS. In addition, after SR, those participants showing higher negative implicit bias toward Arab Muslims tended to consider as more dangerous individuals with more quintessentially untrustworthy facial features (r = 0.76, P = .007), whereas this relationship was nonsignificant after CS (r = 0.33, P = .28). CONCLUSIONS: These findings show not only that SR may increase implicit biases against a particular minority group but that SR also modifies how individuals make explicit decisions about another's trustworthiness based on facial features. These findings may have important implications for many occupations where workers who are routinely restricted of sleep are also responsible for making judgments about other people's trustworthiness (eg, police, security, military personnel).
Simpson NS, Scott-Sutherland J, Gautam S, Sethna N, Haack M. Chronic exposure to insufficient sleep alters processes of pain habituation and sensitization. Pain. 2018;159:33–40.
Publisher's Version
Chronic pain conditions are highly comorbid with insufficient sleep. While the mechanistic relationships between the 2 are not understood, chronic insufficient sleep may be 1 pathway through which central pain-modulatory circuits deteriorate, thereby contributing to chronic pain vulnerability over time. To test this hypothesis, an in-laboratory model of 3 weeks of restricted sleep with limited recovery (5 nights of 4-hour sleep per night followed by 2 nights of 8-hour sleep per night) was compared with 3 weeks of 8-hour sleep per night (control protocol). Seventeen healthy adults participated, with 14 completing both 3-week protocols. Measures of spontaneous pain, heat-pain thresholds, cold-pain tolerance (measuring habituation to cold over several weeks), and temporal summation of pain (examining the slope of pain ratings during cold water immersion) were assessed at multiple points during each protocol. Compared with the control protocol, participants in the sleep-restriction protocol experienced mild increases in spontaneous pain (P < 0.05). Heat-pain thresholds decreased after the first week of sleep restriction (P < 0.05) but normalized with longer exposure to sleep restriction. By contrast, chronic exposure to restricted sleep was associated with decreased habituation to, and increased temporal summation in response to cold pain (both P < 0.05), although only in the past 2 weeks of the sleep-restriction protocol. These changes may reflect abnormalities in central pain-modulatory processes. Limited recovery sleep did not completely resolve these alterations in pain-modulatory processes, indicating that more extensive recovery sleep is required. Results suggest that exposure to chronic insufficient sleep may increase vulnerability to chronic pain by altering processes of pain habituation and sensitization.

2017

Simpson, Haack, Mullington. Sleep and immune regulation. In: Chokroverty, editor. Sleep Disorders Medicine: Basic Science, Technical Considerations and Clinical Aspects. 4th ed. New York, NY, USA: Springer; 2017. pp. 195–203.
Alkozei A, Killgore WD, Smith R, Dailey N, Bajaj S, Haack M. Chronic Sleep Restriction Increases Negative Implicit Attitudes Toward Arab Muslims. Scientific Reports. 2017;7:4285.
Chronic sleep restriction is a common experience; and while it has negative physiological effects, little is known about how it affects human behavior. To date, no study has investigated whether chronic sleep restriction can influence implicit attitudes (e.g., towards a race). Here, in a randomized, counterbalanced crossover design, we subjected participants to 3 weeks of chronic sleep restriction in the lab (i.e., 3 weekly cycles of 5 nights of 4 hours of sleep per night followed by 2 nights of 8 hours of sleep) and found evidence for an increased negative implicit bias towards Arab Muslims. No indicators of an implicit bias were found in these same individuals when they were rested (during a counterbalanced 3-week period of 8 hours time in bed per night). These findings suggest that chronic sleep restriction may "unmask" implicit racial or ethnic biases that are otherwise inhibited when in a rested state. Because chronic sleep restriction is prevalent among many occupations that routinely interact with ethnic minorities in potentially high-conflict situations (e.g., police officers), it is critical to consider the role that restricted sleep may play in exacerbating negative implicit attitudes and their potential for provoking unintentional and potentially harmful behavioral consequences.
Yang H, Haack M, Gautam S, Meier-Ewert HK, Mullington J. Repetitive exposure to shortened sleep leads to blunted sleep-associated blood pressure dipping. Journal of Hypertension. 2017.

Background: Blood pressure (BP) dips at night during sleep in healthy individuals but in disturbed sleep, dipping is blunted. However, the impact of chronic insufficient sleep duration, with limited intermittent recovery sleep, on BP dipping is not known. The objective of this study was to examine, in a controlled experimental model, the influence of chronic sleep restriction on BP patterns at night and during the day.
Method: In a highly controlled 22-day in-hospital protocol, 45 healthy participants (age 322 years; BMI 241kg/m2; 22 men and 23 women) were randomly assigned to one of two conditions: repeated sleep restriction (4 h of sleep/night from 0300 to 0700 h for three nights followed by recovery sleep of 8 h, repeated four times in succession) or a sleep control group (8 h/night from 2300 to 0700 h).
Results: Beat-to-beat BP and polysomnography were recorded and revealed that sleep-associated DBP dipping was significantly blunted during all four blocks of sleep restriction (P¼0.002). Further, DBP was significantly increased for the whole day during the first, second, and fourth block of sleep restriction (all P<0.01), and SBP was significantly increased for the whole day during the first block of sleep restriction.
Conclusion: Repeated exposure to significantly shortened sleep blunts sleep-associated BP dipping, despite intermittent catch-up sleep. Individuals frequently experiencing insufficient sleep may be at increased risk for hypertension due to repetitive blunting of sleep-associated BP dipping, and resultant elevations in average circadian BP.
Keywords: autonomic nervous system, blood pressure, circadian, blood pressure dipping, diurnal, heart rate, sleep deprivation, sodium excretion
Abbreviations: BL, baseline; BP, blood pressure; CRC, clinical research center; CVD, cardiovascular disease; HR, heart rate; N1, N2, N3, stages 1–3 in nonrapid eye movement sleep; Rec, recovery; REM, rapid eye movement; SE, sleep efficiency; TST, total sleep time

2016

Morgenthaler T, Hashmi S, Croft J, Dort L, Heald J, Mullington J. High School Start Times and the Impact on High School Students: What We Know, and What We Hope to Learn. J Clin Sleep Med. 2016;12(12):1681–1689. doi:10.5664/jcsm.6358
STUDY OBJECTIVES: Several organizations have provided recommendations to ensure high school starts no sooner than 08:30. However, although there are plausible biological reasons to support such recommendations, published recommendations have been based largely on expert opinion and a few observational studies. We sought to perform a critical review of published evidence regarding the effect of high school start times on sleep and other relevant outcomes. METHODS: We performed a broad literature search to identify 287 candidate publications for inclusion in our review, which focused on studies offering direct comparison of sleep time, academic or physical performance, behavioral health measures, or motor vehicular accidents in high school students. Where possible, outcomes were combined for meta-analysis. RESULTS: After application of study criteria, only 18 studies were suitable for review. Eight studies were amenable to meta-analysis for some outcomes. We found that later school start times, particularly when compared with start times more than 60 min earlier, are associated with longer weekday sleep durations, lower weekday-weekend sleep duration differences, reduced vehicular accident rates, and reduced subjective daytime sleepiness. Improvement in academic performance and behavioral issues is less established. CONCLUSIONS: The literature regarding effect of school start time delays on important aspects of high school life suggests some salutary effects, but often the evidence is indirect, imprecise, or derived from cohorts of convenience, making the overall quality of evidence weak or very weak. This review highlights a need for higher-quality data upon which to base important and complex public health decisions.
Simpson N, Diolombi M, Scott-Sutherland J, Yang H, Bhatt V, Gautam S, Mullington J, Haack M. Repeating patterns of sleep restriction and recovery: Do we get used to it?. Brain, Behavior, and Immunity. 2016;58:142–151.

Despite its prevalence in modern society, little is known about the long-term impact of restricting sleep during the week and ‘catching up’ on weekends. This common sleep pattern was experimentally modeled with three weeks of 5 nights of sleep restricted to 4 h followed by two nights of 8-h recovery sleep. In an
intra-individual design, 14 healthy adults completed both the sleep restriction and an 8-h control condition, and the subjective impact and the effects on physiological markers of stress (cortisol, the inflammatory marker IL-6, glucocorticoid receptor sensitivity) were assessed. Sleep restriction was not perceived to be subjectively stressful and some degree of resilience or resistance to the effects of sleep restriction was observed in subjective domains. In contrast, physiological stress response systems remain activated with repeated exposures to sleep restriction and limited recovery opportunity. Morning IL-6 expression in monocytes was significantly increased during week 2 and 3 of sleep restriction, and remained
increased after recovery sleep in week 2 (p < 0.05) and week 3 (p < 0.09). Serum cortisol showed a significantly dysregulated 24 h-rhythm during weeks 1, 2, and 3 of sleep restriction, with elevated morning cortisol, and decreased cortisol in the second half of the night. Glucocorticoid sensitivity of monocytes
was increased, rather than decreased, during the sleep restriction and sleep recovery portion of each week. These results suggest a disrupted interplay between the hypothalamic-pituitary-adrenal and inflammatory systems in the context of repeated exposure to sleep restriction and recovery. The observed
dissociation between subjective and physiological responses may help explain why many individuals continue with the behavior pattern of restricting and recovering sleep over long time periods, despite a cumulative deleterious physiological effect.