Sleep disturbance, inflammation and depression risk in cancer survivors

University of California, Los Angeles - Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, CA, United States.
Brain Behavior and Immunity (Impact Factor: 5.89). 05/2012; 30. DOI: 10.1016/j.bbi.2012.05.002
Source: PubMed


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. However, behavioral co-morbidities often arise during treatment and persist long-term to complicate survival and reduce quality of life. In this review, the inter-relationships between cancer, depression, and sleep disturbance are described, with a focus on the role of sleep disturbance as a risk factor for depression. Increasing evidence also links alterations in inflammatory biology dynamics to these long-term effects of cancer diagnosis and treatment, and the hypothesis that sleep disturbance drives inflammation, which together contribute to depression, is discussed. Better understanding of the associations between inflammation and behavioral co-morbidities has the potential to refine prediction of risk and development of strategies for the prevention and treatment of sleep disturbance and depression in cancer survivors.

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    • "E. Cash et al. / Brain, Behavior, and Immunity 48 (2015) 102–114 103 1.1. Circadian effectors of tumor promoting biology (Arrow F in Fig. 1) Clinical data show cancer patients and cancer survivors with clear circadian disruption have related alteration of inflammatory mediators (Rich et al., 2005; Irwin et al., 2013; Bower et al., 2005; Miller et al., 2008). Chronic inflammatory processes affect all stages of tumor development including initiation, promotion, and progression (Elinav et al., 2013). "
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    ABSTRACT: Psychological distress, which can begin with cancer diagnosis and continue with treatment, is linked with circadian and endocrine disruption. In turn, circadian/endocrine factors are potent modulators of cancer progression. We hypothesized that circadian rest-activity rhythm disruption, distress, and diurnal cortisol rhythms would be associated with biomarkers of tumor progression in the peripheral blood of women awaiting breast cancer surgery. Breast cancer patients (n=43) provided actigraphic data on rest-activity rhythm, cancer-specific distress (IES, POMS), saliva samples for assessment of diurnal cortisol rhythm, cortisol awakening response (CAR), and diurnal mean. Ten potential markers of tumor progression were quantified in serum samples and grouped by exploratory factor analysis. Analyses yielded three factors, which appear to include biomarkers reflecting different aspects of tumor progression. Elevated factor scores indicate both high levels and strong clustering among serum signals. Factor 1 included VEGF, MMP-9, and TGF-β; suggesting tumor invasion/immunosuppression. Factor 2 included IL-1β, TNF-α, IL-6R, MCP-1; suggesting inflammation/chemotaxis. Factor 3 included IL-6, IL-12, IFN-γ; suggesting inflammation/TH1-type immunity. Hierarchical regressions adjusting age, stage and socioeconomic status examined associations of circadian, distress, and endocrine variables with these three factor scores. Patients with poor circadian coordination as measured by rest-activity rhythms had higher Factor 1 scores (R(2)=.160, p=.038). Patients with elevated CAR also had higher Factor 1 scores (R(2)=.293, p=.020). These relationships appeared to be driven largely by VEGF concentrations. Distress was not related to tumor-relevant biomarkers, and no other significant relationships emerged. Women with strong circadian activity rhythms showed less evidence of tumor promotion and/or progression as indicated by peripheral blood biomarkers. The study was not equipped to discern the cause of these associations. Circadian/endocrine aberrations may be a manifestation of systemic effects of aggressive tumors. Alternatively, these results raise the possibility that, among patients with active breast tumors, disruption of circadian activity rhythms and elevated CAR may facilitate tumor promotion and progression. Developmental Cancer Research Award, awarded to authors F.S.D., S.E.S., and D.S. from the Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA; University of Louisville Intramural Research Incentive Grant for Research on Women awarded to S.E.S. from the University of Louisville Office of the Vice President for Research; Carl & Elizabeth Naumann Startup Fund awarded to F.S.D. Copyright © 2015. Published by Elsevier Inc.
    Brain Behavior and Immunity 02/2015; 48. DOI:10.1016/j.bbi.2015.02.017 · 5.89 Impact Factor
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    • "It is important to note that some cancer-related sequelae tend to co-occur, prompting research on symptom clusters such as depression, fatigue, and pain (Jaremka et al., 2013; Reyes-Gibby, Aday, Anderson, Mendoza, & Cleeland, 2006). Although some evidence suggests that the experience of sleep disturbance and fatigue may precede the onset of depressive symptoms and pain in the reentry and early survivorship periods (Irwin, Olmstead, Ganz, & Haque, 2013; Trudel-Fitzgerald, Savard, & Ivers, 2013), other research has not established temporal precedence (Krebber et al., 2014). "
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    American Psychologist 02/2015; 70(2):159-174. DOI:10.1037/a0037875 · 6.87 Impact Factor
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    • "The empirical paper by Witek-Jansek et al. in this volume explores whether childhood adversity is associated with vulnerability for intense sustained behavioral symptoms, including fatigue and depressive symptoms, and quality of life and immune dysregulation (Witek Janusek et al., 2012). Irwin and colleagues describe the common presentation of sleep disturbance and depression in cancer survivors (Irwin et al., 2012). The authors outline a model in which sleep disturbance drives alterations in inflammatory biology, which result in of depressive symptoms and in clinical depression for some. "
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