The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

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.

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>50000) were analyzed with assessment of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF). Sleep disturbance was associated with higher levels of CRP (ES 0.12; 95% CI 0.05 – 0.19) and IL-6 (ES 0.20; 95% CI 0.08 – 0.31). Shorter sleep duration, but not the extreme of short sleep, was associated with higher levels of CRP (ES 0.09; 95% CI 0.01 – 0.17) but not IL-6 (ES 0.03; 95% CI −0.09 – 0.14). The extreme of long sleep duration was associated with higher levels of CRP (ES 0.17; 95% CI 0.01 – 0.34) and IL-6 (ES 0.11; 95% CI 0.02 – 0.20). Neither sleep disturbances nor sleep duration was associated with TNF. Neither experimental sleep deprivation nor sleep restriction was associated with CRP, IL-6, or TNF. Some heterogeneity among studies was found, but 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.

Innate immune responses are regulated by microorganisms and cell death, as well as by a third class of stress signal from the nervous and endocrine systems. The innate immune system also feeds back, through the production of cytokines, to regulate the function of the central nervous system (CNS), and this has effects on behaviour. These signals provide an extrinsic regulatory circuit that links physiological, social and environmental conditions, as perceived by the CNS, with transcriptional ‘decision-making’ in leukocytes. CNS-mediated regulation of innate immune responses optimizes total organism fitness and provides new opportunities for therapeutic control of chronic infectious, inflammatory and neuropsychiatric diseases.

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 antiviral immune responses with consequences for vaccine responses and infectious disease risk, and on 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. Lastly 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.

Sleep loss induces a functional alteration of the monocyte proinflammatory cytokine response. A modest amount of sleep loss also alters molecular processes that drive cellular immune activation and induce inflammatory cytokines; mapping the dynamics of sleep loss on molecular signaling pathways has implications for understanding the role of sleep in altering immune cell physiologic characteristics. Interventions that target sleep might constitute new strategies to constrain inflammation with effects on inflammatory disease risk.

Lonely older adults have increased expression of pro-inflammatory genes as well as increased risk for morbidity and mortality. Previous behavioral treatments have attempted to reduce loneliness and its concomitant health risks, but have had limited success. The present study tested whether the 8-week Mindfulness-Based Stress Reduction (MBSR) program (compared to a Wait-List control group) reduces loneliness and downregulates loneliness-related pro-inflammatory gene expression in older adults (N=40). Consistent with study predictions, mixed effect linear models indicated that the MBSR program reduced loneliness, compared to small increases in loneliness in the control group (treatment condition × time interaction: F(1,35)=7.86, p=.008). Moreover, at baseline, there was an association between reported loneliness and upregulated pro-inflammatory NF-κB-related gene expression in circulating leukocytes, and MBSR downregulated this NF-κB-associated gene expression profile at post-treatment. Finally, there was a trend for MBSR to reduce C Reactive Protein (treatment condition × time interaction: (F(1,33)=3.39, p=.075). This work provides an initial indication that MBSR may be a novel treatment approach for reducing loneliness and related pro-inflammatory gene expression in older adults.

No abstract