Sleep has a critical role in promoting health. Research over the past decade has documented that sleep disturbance has a powerful influence on the risk of infectious disease, the occurrence and ...progression of several major medical illnesses including cardiovascular disease and cancer, and the incidence of depression. Increasingly, the field has focused on identifying the biological mechanisms underlying these effects. This review highlights the impact of sleep on adaptive and innate immunity, with consideration of the dynamics of sleep disturbance, sleep restriction, and insomnia on (
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) antiviral immune responses with consequences for vaccine responses and infectious disease risk and (
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) proinflammatory immune responses with implications for cardiovascular disease, cancer, and depression. This review also discusses the neuroendocrine and autonomic neural underpinnings linking sleep disturbance and immunity and the reciprocal links between sleep and inflammatory biology. Finally, interventions are discussed as effective strategies to improve sleep, and potential opportunities are identified to promote sleep health for therapeutic control of chronic infectious, inflammatory, and neuropsychiatric diseases.
The discovery of reciprocal connections between the central nervous system, sleep and the immune system has shown that sleep enhances immune defences and that afferent signals from immune cells ...promote sleep. One mechanism by which sleep is proposed to provide a survival advantage is in terms of supporting a neurally integrated immune system that might anticipate injury and infectious threats. However, in modern times, chronic social threats can drive the development of sleep disturbances in humans, which can contribute to the dysregulation of inflammatory and antiviral responses. In this Review, I describe our current understanding of the relationship between sleep dynamics and host defence mechanisms, with a focus on cytokine responses, the neuroendocrine and autonomic pathways that connect sleep with the immune system and the role of inflammatory peptides in the homeostatic regulation of sleep. Furthermore, I discuss the therapeutic potential of harnessing these reciprocal mechanisms of sleep-immune regulation to mitigate the risk of inflammatory and infectious diseases.
Nearly half of all adults older than 60 years of age report sleep disturbance, as characterised either by reports of insomnia complaints with daytime consequences, dissatisfaction with sleep quality ...or quantity, or the diagnosis of insomnia disorder. Accumulating evidence shows that sleep disturbance contributes to cognitive decline and might also increase the risk of Alzheimer's disease dementia by increasing β-amyloid burden. That sleep disturbance would be a candidate risk factor for Alzheimer's disease might seem surprising, given that disturbed sleep is usually considered a consequence of Alzheimer's disease. However, a bidirectional relationship between sleep and Alzheimer's disease is supported by advances in our understanding of sleep disturbance-induced increases in systemic inflammation, which can be viewed as an early event in the course of Alzheimer's disease. Inflammation increases β-amyloid burden and is thought to drive Alzheimer's disease pathogenesis. Improved understanding of the mechanisms linking sleep disturbance and Alzheimer's disease risk could facilitate the identification of targets for prevention, given that both sleep disturbance and inflammatory activation might be modifiable risk factors for Alzheimer's disease.
Psychological and health-restorative benefits of mind-body therapies have been investigated, but their impact on the immune system remain less defined.
To conduct the first comprehensive review of ...available controlled trial evidence to evaluate the effects of mind-body therapies on the immune system, focusing on markers of inflammation and anti-viral related immune responses.
Data sources included MEDLINE, CINAHL, SPORTDiscus, and PsycINFO through September 1, 2013. Randomized controlled trials published in English evaluating at least four weeks of Tai Chi, Qi Gong, meditation, or Yoga that reported immune outcome measures were selected. Studies were synthesized separately by inflammatory (n = 18), anti-viral related immunity (n = 7), and enumerative (n = 14) outcomes measures. We performed random-effects meta-analyses using standardized mean difference when appropriate.
Thirty-four studies published in 39 articles (total 2, 219 participants) met inclusion criteria. For inflammatory measures, after 7 to 16 weeks of mind-body intervention, there was a moderate effect on reduction of C-reactive protein (effect size ES, 0.58; 95% confidence interval CI, 0.04 to 1.12), a small but not statistically significant reduction of interleukin-6 (ES, 0.35; 95% CI, -0.04 to 0.75), and negligible effect on tumor necrosis factor-α (ES, 0.21; 95% CI, -0.15 to 0.58). For anti-viral related immune and enumerative measures, there were negligible effects on CD4 counts (ES, 0.15; 95% CI, -0.04 to 0.34) and natural killer cell counts (ES, 0.12, 95% CI -0.21 to 0.45). Some evidence indicated mind-body therapies increase immune responses to vaccination.
Mind-body therapies reduce markers of inflammation and influence virus-specific immune responses to vaccination despite minimal evidence suggesting effects on resting anti-viral or enumerative measures. These immunomodulatory effects, albeit incomplete, warrant further methodologically rigorous studies to determine the clinical implications of these findings for inflammatory and infectious disease outcomes.
Sleep disturbances including insomnia independently contribute to risk of inflammatory disorders and major depressive disorder. This review and overview provides an integrated understanding of the ...reciprocal relationships between sleep and the innate immune system and considers the role of sleep in the nocturnal regulation of the inflammatory biology dynamics; the impact of insomnia complaints, extremes of sleep duration, and experimental sleep deprivation on genomic, cellular, and systemic markers of inflammation; and the influence of sleep complaints and insomnia on inflammaging and molecular processes of cellular aging. Clinical implications of this research include discussion of the contribution of sleep disturbance to depression and especially inflammation-related depressive symptoms. Reciprocal action of inflammatory mediators on the homeostatic regulation of sleep continuity and sleep macrostructure, and the potential of interventions that target insomnia to reverse inflammation, are also reviewed. Together, interactions between sleep and inflammatory biology mechanisms underscore the implications of sleep disturbance for inflammatory disease risk, and provide a map to guide the development of treatments that modulate inflammation, improve sleep, and promote sleep health.
Major life stressors, especially those involving interpersonal stress and social rejection, are among the strongest proximal risk factors for depression. In this review, we propose a biologically ...plausible, multilevel theory that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental stress with internal biological processes that drive depression pathogenesis. Central to this social signal transduction theory of depression is the hypothesis that experiences of social threat and adversity up-regulate components of the immune system involved in inflammation. The key mediators of this response, called proinflammatory cytokines, can in turn elicit profound changes in behavior, which include the initiation of depressive symptoms such as sad mood, anhedonia, fatigue, psychomotor retardation, and social-behavioral withdrawal. This highly conserved biological response to adversity is critical for survival during times of actual physical threat or injury. However, this response can also be activated by modern-day social, symbolic, or imagined threats, leading to an increasingly proinflammatory phenotype that may be a key phenomenon driving depression pathogenesis and recurrence, as well as the overlap of depression with several somatic conditions including asthma, rheumatoid arthritis, chronic pain, metabolic syndrome, cardiovascular disease, obesity, and neurodegeneration. Insights from this theory may thus shed light on several important questions including how depression develops, why it frequently recurs, why it is strongly predicted by early life stress, and why it often co-occurs with symptoms of anxiety and with certain physical disease conditions. This work may also suggest new opportunities for preventing and treating depression by targeting inflammation.
Abstract Background Sleep disturbance is associated with inflammatory disease risk and all-cause mortality. Here, we assess global evidence linking sleep disturbance, sleep duration, and inflammation ...in adult humans. Methods A systematic search of English language publications was performed, with inclusion of primary research articles that characterized sleep disturbance and/or sleep duration or performed experimental sleep deprivation and assessed inflammation by levels of circulating markers. Effect sizes (ES) and 95% confidence intervals (CI) were extracted and pooled using a random effect model. Results A total of 72 studies ( n > 50,000) were analyzed with assessment of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNFα). Sleep disturbance was associated with higher levels of CRP (ES .12; 95% CI = .05–.19) and IL-6 (ES .20; 95% CI = .08–.31). Shorter sleep duration, but not the extreme of short sleep, was associated with higher levels of CRP (ES .09; 95% CI = .01–.17) but not IL-6 (ES .03; 95% CI: −.09 to .14). The extreme of long sleep duration was associated with higher levels of CRP (ES .17; 95% CI = .01–.34) and IL-6 (ES .11; 95% CI = .02–20). Neither sleep disturbances nor sleep duration was associated with TNFα. Neither experimental sleep deprivation nor sleep restriction was associated with CRP, IL-6, or TNFα. Some heterogeneity among studies was found, but there was no evidence of publication bias. Conclusions Sleep disturbance and long sleep duration, but not short sleep duration, are associated with increases in markers of systemic inflammation.
•Inflammation contributes to the pathophysiology of depression.•Inflammatory markers can be used to identify risk and to predict treatment response in depression.•Targeting anti-inflammatory ...mechanisms show potential in the treatment in depression.•Inflammatory profiling can refine clinical decision-making for depression treatment.
Depression, one of the most common mental health disorders, is among the leading causes of health-related disability worldwide. Although antidepressant treatment has been available for decades, depression remains largely refractory to the prevailing limited treatment approach of monoamine transmission modulation. Fortunately, recent evidence points to a link between depression and inflammatory factors within the innate and the adaptive immune system. The purpose of this review is to evaluate current and potential clinical immunotherapies for depression, as contextually focused by an immunologic lens of the pathophysiologic mechanisms of depression. The utility of pro-inflammatory cytokines (primarily interleukin-1β, interleukin -6 and tumor necrosis factor-α) is considered in their role as screening biomarkers in prediction of treatment response or nonresponse. The evidence base of numerous recent clinical studies is discussed as related to their antidepressant efficacy and favorable safety profile, with consideration of multiple agents that target inflammatory mechanisms linked to depression including nonsteroidal anti-inflammatory pathways (i.e., aspirin, celecoxib), cytokine antagonism (i.e., etanercept, infliximab), N-methyl-D-aspartate receptor (NMDA) receptor antagonism (i.e., ketamine), and modulation of kynurenine pathways (i.e., minocycline). Additionally, new and exciting directions in targeting inflammatory mechanisms in the treatment of depression are underway, and future investigation is also warranted to explore the utility of inflammation in diagnosing depression, guiding clinical treatment decision-making, and monitoring disease burden and relapse risk.
Highlights • 26 randomized controlled trials of Tai Chi, Qigong, yoga, and meditation reviewed. • Trials showed consistent reductions in genomic markers of inflammation. • Mixed effects on ...circulating and cellular inflammatory markers.
Over two-thirds of the 11.4 million cancer survivors in the United States can expect long-term survival, with many others living with cancer as a chronic disease controlled by ongoing therapy. ...Behavioral comorbidities often arise during treatment and persist long term to complicate survival and reduce quality of life. This review focuses on depression and insomnia with an emphasis on understanding the role of cancer-specific factors and their contribution to the prevalence of these behavioral comorbidities in cancer patients following cancer diagnosis and treatment. The clinical significance of depression and insomnia for cancer patients is further stressed by epidemiological observations that link depression and insomnia to cancer morbidity and mortality risk.
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