Publications

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.

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.

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.

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.

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.

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.

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.

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.

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.