Publications

2020
Gaffey AE, Redeker NS, Rosman L, Mullington JM, Brandt CA, Haskell SG, Burg MM. The role of insomnia in the association between posttraumatic stress disorder and hypertension. J Hypertens. 2020;38 (4) :641-648.Abstract
OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with incident hypertension. Although this relationship is poorly understood, PTSD is also associated with insomnia symptoms, which increases the risk for hypertension. Whether insomnia contributes to PTSD-associated risk for hypertension is unknown. METHODS: We examined self-report survey and electronic health record data from 1109 participants in the Women Veterans Cohort Study (mean age: 43.8 ± 10.9 years; 52% women, 81% White) to assess the cross-sectional associations between PTSD symptom severity, recent symptoms of insomnia, and hypertension, defined as self-reported treatment for high blood pressure in the last year. Structural equation modeling was used to examine whether insomnia symptoms mediate the association between PTSD and hypertension. RESULTS: PTSD symptom severity was associated with hypertension (r = 0.09, P < 0.001). PTSD symptom severity and hypertension were each associated with the insomnia symptoms difficulty falling asleep, difficulty staying asleep, and worry/distress about sleep problems (PTSD: rs = 0.58--0.62, P <  0.001; hypertension: rs = 0.07--0.10, P <  0.001). A latent variable derived from those symptoms mediated 9% of the association between PTSD symptom severity and hypertension (P = 0.02). CONCLUSION: In this study of young and middle-aged Veterans, insomnia symptoms mediated the association between PTSD and hypertension. Difficulties falling asleep and maintaining sleep and related distress may be particularly deleterious for cardiovascular health in Veterans. Longitudinal data is required to further investigate the associations between PTSD, insomnia, and hypertension.
Haspel JA, Anafi R, Brown MK, Cermakian N, Depner C, Desplats P, Gelman AE, Haack M, Jelic S, Kim BS, et al. Perfect timing: circadian rhythms, sleep, and immunity - an NIH workshop summary. JCI Insight. 2020;5 (1).Abstract
Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate and adaptive immune responses - ranging from leukocyte mobilization, trafficking, and chemotaxis to cytokine release and T cell differentiation -are mediated in a time of day-dependent manner. The National Institutes of Health (NIH) recently sponsored an interdisciplinary workshop, "Sleep Insufficiency, Circadian Misalignment, and the Immune Response," to highlight new research linking sleep and circadian biology to immune function and to identify areas of high translational potential. This Review summarizes topics discussed and highlights immediate opportunities for delineating clinically relevant connections among biological rhythms, sleep, and immune regulation.
Haack M, Simpson N, Sethna N, Kaur S, Mullington J. Sleep deficiency and chronic pain: potential underlying mechanisms and clinical implications. Neuropsychopharmacology. 2020;45 (1) :205-216.Abstract
Pain can be both a cause and a consequence of sleep deficiency. This bidirectional relationship between sleep and pain has important implications for clinical management of patients, but also for chronic pain prevention and public health more broadly. The review that follows will provide an overview of the neurobiological evidence of mechanisms thought to be involved in the modulation of pain by sleep deficiency, including the opioid, monoaminergic, orexinergic, immune, melatonin, and endocannabinoid systems; the hypothalamus-pituitary-adrenal axis; and adenosine and nitric oxide signaling. In addition, it will provide a broad overview of pharmacological and non-pharmacological approaches for the management of chronic pain comorbid with sleep disturbances and for the management of postoperative pain, as well as discuss the effects of sleep-disturbing medications on pain amplification.
2019
Mullington JM. Please forgive our appearance while under biomarker construction. Sleep. 2019;42 (1).
Makarem N, Shechter A, Carnethon MR, Mullington JM, Hall MH, Abdalla M. Sleep Duration and Blood Pressure: Recent Advances and Future Directions. Curr Hypertens Rep. 2019;21 (5) :33.Abstract
PURPOSE OF REVIEW: This review discusses the recent literature on subjectively and objectively assessed sleep duration in relation to hypertension risk and out-of-clinic blood pressure (BP) measures and highlights critical areas for future research. RECENT FINDINGS: Sleep duration, particularly short sleep, may influence BP through disturbed autonomic balance, hormonal imbalances, increased adiposity and metabolic dysfunction, and disrupted circadian rhythms. Observational studies indicate that short and long sleep are associated with hypertension risk, reduced nocturnal dipping, and elevated morning BP, but evidence is stronger for short sleep. Experimental sleep restriction increases BP, while sleep extension may lower BP in prehypertensive individuals. Women and racial/ethnic minorities are more prone to the detrimental effects of short sleep on BP. Additional studies are warranted to clarify the association of objectively assessed sleep with BP level and diurnal pattern and to determine the sex- and race-specific effects of sleep restriction and extension on BP.
Redeker NS, Caruso CC, Hashmi SD, Mullington JM, Grandner M, Morgenthaler TI. Workplace Interventions to Promote Sleep Health and an Alert, Healthy Workforce. J Clin Sleep Med. 2019;15 (4) :649-657.Abstract
STUDY OBJECTIVES: The purpose of this review is to synthesize the published literature that addresses employer-initiated interventions to improve the sleep of workers and in turn improve health, productivity, absenteeism, and other outcomes that have been associated with sleep disorders or sleep deficiency. METHODS: We conducted a systematic search and a selective narrative review of publications in PubMed from 1966 to December 2017. We extracted study characteristics, including the workers' professions, workplace settings and shift work, and workplace interventions focused on worker sleep. Because of the high degree of heterogeneity in design and outcomes, we conducted a narrative review. RESULTS: We identified 219 publications. After restriction to publications with studies of workplace interventions that evaluated the outcomes of sleep duration or quality, we focused on 47 articles. An additional 13 articles were accepted in the pearling process. Most studies employed non-randomized or controlled pretest and posttest designs and self-reported measures of sleep. The most common workplace interventions were educational programs stressing sleep hygiene or fatigue management. Other interventions included timed napping before or after work, urging increased daytime activity levels, modifying workplace environmental characteristics such as lighting, and screening, and referral for sleep disorders treatment. Overall, most reports indicated that employer efforts to encourage improved sleep hygiene and healthier habits result in improvements in sleep duration, sleep quality, and self-reported sleepiness complaints. CONCLUSIONS: These studies suggest employer-sponsored efforts can improve sleep and sleep-related outcomes. The existing evidence, although weak, suggests efforts by employers to encourage better sleep habits and general fitness result in self-reported improvements in sleep-related outcomes, and may be associated with reduced absenteeism and better overall quality of life. Candidate workplace strategies to promote sleep health are provided.
Berger KI, Kanters S, Jansen JP, Stewart A, Sparks S, Haack KA, Bolzani A, Siliman G, Hamed A. Forced vital capacity and cross-domain late-onset Pompe disease outcomes: an individual patient-level data meta-analysis. J Neurol. 2019;266 (9) :2312-2321.Abstract
BACKGROUND: Late-onset Pompe disease (LOPD) is a rare, metabolic disease primarily affecting the musculoskeletal and respiratory systems. Forced vital capacity (FVC) is commonly used to measure pulmonary function; however, associations between FVC and other LOPD outcomes remain unclear. METHODS: A systematic literature review was conducted on November 2015, updated September 2016 and supplemented with clinical trial data from the sponsor. Outcomes included: 6-min walk test distance (6MWT), FVC, maximal inspiratory/expiratory pressure (MIP/MEP), Medical Research Council-skeletal muscle strength score (MRC), 36-item short-form survey-physical component score (SF-36), Rotterdam Handicap Scale (RHS), Fatigue Severity Scale (FSS) and survival. Individual patient data meta-analysis was used for cross-sectional analyses and longitudinal analyses to determine associations between percent of predicted FVC and LOPD measures and outcomes. RESULTS: Fifteen studies were selected. From cross-sectional analyses, FVC and MRC were most strongly associated. Specifically, patients with 10% higher FVC (a round number for illustrative purposes only) were associated with a 4.72% (95% confidence interval [CI]: 3.37, 6.07) higher MRC score, indicating a positive association. Similarly, slopes for the 6MWT and SF-36 relative to a 10% higher FVC were estimated at 33.2 meters (95% CI 24.0, 42.4) and 1.2% (95% CI 0.24, 2.16%), respectively. From longitudinal analyses, a 10% incremental increase in predicted FVC was associated with an average increase of 4.12% in MRC score (95% CI 1.29, 6.95), 35.6 m in the 6MWT (95% CI 19.9, 51.6), and 1.34% in SF-36 (95% CI 0.08, 2.60). There was insufficient data to conduct analyses for RHS, FSS and survival. CONCLUSIONS: FVC is positively associated with LOPD measures and outcomes across multiple domains. Additionally, longitudinal changes in FVC are positively associated with changes in the 6MWT, MRC and SF-36.
Devine JK, Bertisch SM, Yang H, Scott-Sutherland J, Wilkins A, Molina V, Henrikson K, Haack M. Glucocorticoid and inflammatory reactivity to a repeated physiological stressor in insomnia disorder. Neurobiol Sleep Circadian Rhythms. 2019;6 :77-84.Abstract
Despite known associations of insomnia disorder with alterations in cytokine and glucocorticoid (GC) production, neither the sensitivity of immune cells to a GC signal nor the reactivity of the hypothalamus-pituitary-adrenal (HPA) axis and inflammatory system to stress, or adaptation of these systems to repeated stress have been assessed in patients with insomnia. To investigate potential dysregulation in stress reactivity and adaptation to repeated exposure, a physiological stressor (the cold pressor test; CPT) was repeatedly administered to N = 20 participants with insomnia disorder (based on DSM-V, 18 females, age 30 ± 2.5 years) and N = 20 sex-matched healthy controls following an at-home actigraphy and in-laboratory PSG. HPA and inflammatory markers (serum cortisol, plasma interleukin [IL]-6) were measured at baseline/resting levels and following each of the three CPTs. In addition, sensitivity of monocytes to the synthetic GC dexamethasone was assessed in-vitro at baseline levels in order to examine the cortisol-IL-6 interplay at the cell level. Compared to healthy controls, individuals with insomnia disorder exhibited shorter sleep duration as assessed by actigraphy and PSG (p ≤ 0.05). HPA, but not inflammatory reactivity to the repeated CPT challenge was greater in insomnia disorder (p ≤ 0.05 for group effect), due to greater cortisol responses to the initial CPT (p ≤ 0.05). There were no between-group differences in the ability of the HPA to adapt to stress repetition nor in basal/resting levels of cortisol, IL-6, and GC sensitivity. These findings suggest that insomnia disorder potentiates HPA axis reactivity to initial/novel stressors, which may constitute a pathway underlying adverse health consequences in the long term.
Yang H, Haack M, Dang R, Gautam S, Simpson NS, Mullington JM. Heart rate variability rebound following exposure to persistent and repetitive sleep restriction. Sleep. 2019;42 (2).Abstract
While it is well established that slow-wave sleep electroencephalography (EEG) rebounds following sleep deprivation, very little research has investigated autonomic nervous system recovery. We examined heart rate variability (HRV) and cardiovagal baroreflex sensitivity (BRS) during four blocks of repetitive sleep restriction and sequential nights of recovery sleep. Twenty-one healthy participants completed the 22-day in-hospital protocol. Following three nights of 8-hr sleep, they were assigned to a repetitive sleep restriction condition. Participants had two additional 8-hr recovery sleep periods at the end of the protocol. Sleep EEG, HRV, and BRS were compared for the baseline, the four blocks of sleep restriction, and the second (R2) and third (R3) nocturnal recovery sleep periods following the last sleep restriction block. Within the first hour of each sleep period, vagal activation, as indexed by increase in high frequency (HF; HRV spectrum analysis), showed a rapid increase, reaching its 24-hr peak. HF was more pronounced (rebound) in R2 than during baseline (p < 0.001). The BRS increased within the first hour of sleep and was higher across all sleep restriction blocks and recovery nights (p = 0.039). Rebound rapid eye movement sleep was observed during both R2 and R3 (p = 0.004), whereas slow-wave sleep did not differ between baseline and recovery nights (p > 0.05). Our results indicate that the restoration of autonomic homeostasis requires a time course that includes at least three nights, following an exposure to multiple nights of sleep curtailed to about half the normal nightly amount.
Lazaridou A, Koulouris A, Devine JK, Haack M, Jamison RN, Edwards RR, Schreiber KL. Impact of daily yoga-based exercise on pain, catastrophizing, and sleep amongst individuals with fibromyalgia. J Pain Res. 2019;12 :2915-2923.Abstract
Background: Fibromyalgia (FM) is a chronic widespread pain disorder characterized by negative affect, sleep disturbance, and fatigue. This uncontrolled pilot study investigated the efficacy of daily yoga-based exercise to improve FM symptoms and explored baseline phenotypic characteristics associated with the greatest benefit. Methods: FM patients (n=46, with 36 completers) reported psychosocial functioning and a range of FM symptoms using validated instruments before and after participation in Satyananda yoga, which included weekly in-person pain-tailored group classes for 6 weeks and daily home yoga video practice. Results: Changes in FM symptoms from pre- to post-yoga were variable amongst participants. Group means for pain decreased, as reported by average daily diary and Brief Pain Inventory, with greater home practice minutes associated with a greater decrease in pain. Average daily ratings of sleep and fatigue improved. Pain catastrophizing was decreased overall, with greater change correlated to a decrease in FM symptoms. We did not observe any group mean changes in actigraphy sleep efficiency, Patient-Reported Outcomes Measurement Information System-anxiety and the Revised Fibromyalgia Impact Questionnaire. Multilevel Modeling analysis revealed a significant interaction between anxiety and catastrophizing for end-study sleep efficiency, fatigue, and pain, such that patients with higher baseline catastrophizing and lower baseline anxiety reported less pain and fatigue, and higher sleep efficiency after the sixth week of yoga practice. Conclusion: This pilot study suggests that yoga may reduce pain and catastrophizing, as well as improve sleep, but these changes were modest across study participants. Greater uptake of home yoga practice as well as a phenotype of higher baseline catastrophizing combined with lower baseline anxiety were associated with greater impact. Future randomized, controlled trials comparing different types of yoga or exercise will allow determination of the most effective treatments for FM and allow closer targeting to the patients who will benefit most from them.
Besedovsky L, Lange T, Haack M. The sleep-immune crosstalk in health and disease. Physiological Reviews [Internet]. 2019;99 (3) :1325-1380. Publisher's VersionAbstract
Sleep and immunity are bidirectionally linked. Immune system activation
alters sleep, and sleep in turn affects the innate and adaptive arm of our body’s defense
system. Stimulation of the immune system by microbial challenges triggers an inflammatory
response, which, depending on its magnitude and time course, can induce an increase in sleep
duration and intensity, but also a disruption of sleep. Enhancement of sleep during an infection is
assumed to feedback to the immune system to promote host defense. Indeed, sleep affects various
immune parameters, is associated with a reduced infection risk, and can improve infection outcome
and vaccination responses. The induction of a hormonal constellation that supports immune functions
is one likely mechanism underlying the immune-supporting effects of sleep. In the absence of an
infectious challenge, sleep appears to promote inflammatory homeostasis through effects on several
inflammatory mediators, such as cytokines. This notion is supported by findings that prolonged sleep
deficiency (e.g., short sleep duration, sleep disturbance) can lead to chronic, systemic low-grade
inflammation and is associated with various diseases that have an inflammatory component, like
diabetes, atherosclerosis, and neurodegeneration. Here, we review available data on this regulatory
sleep-immune crosstalk, point out methodological challenges, and suggest questions open for future
research.
besedovsky_2019_physiol_rev.pdf
2018
Grandner M, Mullington JM, Hashmi SD, Redeker NS, Watson NF, Morgenthaler TI. Sleep Duration and Hypertension: Analysis of > 700,000 Adults by Age and Sex. J Clin Sleep Med. 2018;14 (6) :1031-1039.Abstract
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.
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 (1) :33-40.Abstract
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.
Alkozei A, Haack M, Skalamera J, Smith R, Satterfield BC, Raikes AC, Killgore WD. Chronic sleep restriction affects the association between implicit bias and explicit social decision making. Sleep Health. 2018;4 (5) :456-462.Abstract
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).
Alkozei A, Killgore WD, Smith R, Dailey NS, Bajaj S, Raikes AC, Haack M. Chronic sleep restriction differentially affects implicit biases toward food among men and women: preliminary evidence. J Sleep Res. 2018;27 (4) :e12629.Abstract
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.
Baker K, Gordon SL, Melland H, Bumbak F, Scott DJ, Jiang TJ, Owen D, Turner BJ, Boyd SG, Rossi M, et al. SYT1-associated neurodevelopmental disorder: a case series. Brain. 2018;141 (9) :2576-2591.Abstract
Synaptotagmin 1 (SYT1) is a critical mediator of fast, synchronous, calcium-dependent neurotransmitter release and also modulates synaptic vesicle endocytosis. This paper describes 11 patients with de novo heterozygous missense mutations in SYT1. All mutations alter highly conserved residues, and cluster in two regions of the SYT1 C2B domain at positions Met303 (M303K), Asp304 (D304G), Asp366 (D366E), Ile368 (I368T) and Asn371 (N371K). Phenotypic features include infantile hypotonia, congenital ophthalmic abnormalities, childhood-onset hyperkinetic movement disorders, motor stereotypies, and developmental delay varying in severity from moderate to profound. Behavioural characteristics include sleep disturbance and episodic agitation. Absence of epileptic seizures and normal orbitofrontal head circumference are important negative features. Structural MRI is unremarkable but EEG disturbance is universal, characterized by intermittent low frequency high amplitude oscillations. The functional impact of these five de novo SYT1 mutations has been assessed by expressing rat SYT1 protein containing the equivalent human variants in wild-type mouse primary hippocampal cultures. All mutant forms of SYT1 were expressed at levels approximately equal to endogenous wild-type protein, and correctly localized to nerve terminals at rest, except for SYT1M303K, which was expressed at a lower level and failed to localize at nerve terminals. Following stimulation, SYT1I368T and SYT1N371K relocalized to nerve terminals at least as efficiently as wild-type SYT1. However, SYT1D304G and SYT1D366E failed to relocalize to nerve terminals following stimulation, indicative of impairments in endocytic retrieval and trafficking of SYT1. In addition, the presence of SYT1 variants at nerve terminals induced a slowing of exocytic rate following sustained action potential stimulation. The extent of disturbance to synaptic vesicle kinetics is mirrored by the severity of the affected individuals' phenotypes, suggesting that the efficiency of SYT1-mediated neurotransmitter release is critical to cognitive development. In summary, de novo dominant SYT1 missense mutations are associated with a recognizable neurodevelopmental syndrome, and further cases can now be diagnosed based on clinical features, electrophysiological signature and mutation characteristics. Variation in phenotype severity may reflect mutation-specific impact on the diverse physiological functions of SYT1.
Simpson NS, Scott-Sutherland J, Gautam S, Sethna N, Haack M. Chronic exposure to insufficient sleep alters processes of pain habituation and sensitization. Pain [Internet]. 2018;159 :33-40. Publisher's VersionAbstract
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.
simpson_pain_2018.pdf
2017
Morgenthaler TI, Dort L, Mullington J. Transparency and Partnership. J Clin Sleep Med. 2017;13 (5) :763.
Alkozei A, Killgore WD, Smith R, Dailey NS, Bajaj S, Haack M. Chronic Sleep Restriction Increases Negative Implicit Attitudes Toward Arab Muslims. Sci Rep. 2017;7 (1) :4285.Abstract
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 JM. Repetitive exposure to shortened sleep leads to blunted sleep-associated blood pressure dipping. J Hypertens. 2017;35 (6) :1187-1194.Abstract
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 32 ± 2 years; BMI 24 ± 1 kg/m; 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 (P = 0.002). 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.

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