Sleep quality is important to health, and increasingly viewed as critical in promoting successful, resilient aging. In this review, the interplay between sleep and mental and physical health is considered with a focus on the role of inflammation as a biological pathway that translates the effects of sleep on risk of depression, pain and chronic disease risk in aging. Given that sleep regulates inflammatory biologic mechanisms with effects on mental and physical health outcomes, the potential of interventions that target sleep to reduce inflammation and promote health in aging is also discussed.

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 (a) antiviral immune responses with consequences for vaccine responses and infectious disease risk and (b) 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.

Thermoregulation and sleep are tightly coordinated, with evidence that impairments in thermoregulation as well as increases in ambient temperature increase the risk of sleep disturbance. As a period of rest and low demand for metabolic resources, sleep functions to support host responses to prior immunological challenges. In addition by priming the innate immune response, sleep prepares the body for injury or infection which might occur the following day. However when sleep is disrupted, this phasic organization between nocturnal sleep and the immune system becomes misaligned, cellular and genomic markers of inflammation are activated, and increases of proinflammatory cytokines shift from the nighttime to the day. Moreover, when sleep disturbance is perpetuated due to thermal factors such as elevated ambient temperature, the beneficial crosstalk between sleep and immune system becomes further imbalanced. Elevations in proinflammatory cytokines have reciprocal effects and induce sleep fragmentation with decreases in sleep efficiency, decreases in deep sleep, and increases in rapid eye movement sleep, further fomenting inflammation and inflammatory disease risk. Under these conditions, sleep disturbance has additional potent effects to decrease adaptive immune response, impair vaccine responses, and increase vulnerability to infectious disease. Behavioral interventions effectively treat insomnia and reverse systemic and cellular inflammation. Further, insomnia treatment redirects the misaligned inflammatory- and adaptive immune transcriptional profiles with the potential to mitigate risk of inflammation-related cardiovascular, neurodegenerative, and mental health diseases, as well as susceptibility to infectious disease.

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.

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.

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.

Sleep and pain are critical homeostatic systems that interact in a bidirectional manner. Complaints of sleep disturbance are ubiquitous among patients with chronic pain disorders, and conversely, patients with persistent insomnia symptoms commonly report suffering from chronic pain. Sleep deprivation paradigms demonstrate that partial or complete sleep loss induce hyperalgesia, possibly due to shared mechanistic pathways including neuroanatomic and molecular substrates. Further, chronic pain conditions and sleep disturbances are intertwined through comorbidities, which together cause detrimental psychological and physical consequences. This critical review examines 29 polysomnography studies to evaluate whether nonmalignant chronic pain patients, as compared to controls, show differences in objective measures of sleep continuity and sleep architecture. Whereas these controlled studies did not reveal a consistent pattern of objective sleep disturbances, alterations of sleep continuity were commonly reported. Alterations of sleep architecture such as increases in light sleep or decreases in slow-wave sleep were less commonly reported and findings were mixed and also inconsistent. Methodological flaws were identified, which complicated interpretation and limited conclusions; hence, recommendations for future research are suggested. Knowledge of abnormalities in the sleep process has implications for understanding the pathophysiology of chronic pain conditions, which might also direct the development of novel intervention strategies.

Self-reported health (SRH) has been consistently shown to predict morbidity and mortality. However, the mechanisms underlying this association are poorly understood. The study by Cohen and colleagues reported in this issue of Psychosomatic Medicine fills this gap by examining a potential biological mechanism: alteration of immune system functioning. The study shows that SRH predicted common cold after experimentally controlled virus inoculation in healthy individuals. More specifically, SRH predicted the cold-related illness expression as measured by objective clinical signs, whereas it did not predict the infection rates as measured by predefined increases in specific antibodies. This editorial discusses the significance of this study and the possibility that inflammation, an innate immune response, is a link between SRH and common cold risk. Because the illness expression of cold is generally attributed to increased local inflammation and SRH has been found associated with increased systemic inflammation, it is possible that SRH is a correlate of a heightened systemic inflammatory state and thus leads to increased local inflammatory responses after an exposure to a cold virus. SRH was also associated with well-known risk factors for inflammation in this study, such as overweight, perceived stress, and social isolation. Because of the strong predictive value of SRH for future morbidity and mortality and the simple low-cost tools that enable its assessment, SRH has the potential to identify high-risk individuals in various public health settings. Future research is needed to address the translational applicability of these findings and to further the mechanistic investigation in high-risk groups including older adults.