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  • br Conclusions Results are consistent


    Conclusions: Results are Actinomycin D consistent with the hypothesis that eudaimonic well-being may be an important me-chanism in interventions aimed at enhancing health in vulnerable groups, and contribute to our understanding of how psychological well-being may influence physical health in cancer patients.
    1. Introduction
    Chronic adversity and distress are associated with higher risk of morbidity and early mortality (Holt-Lunstad et al., 2015; Penninx et al., 2013). There is increasing evidence that this relationship is mediated at least in part by stress-induced modulation of immunological processes, including alterations in inflammatory and anti-viral responses (Miller
    et al., 2011; Rohleder, 2016). Individuals exposed to trauma (Kohrt et al., 2016), chronic loneliness (Cole et al., 2015), caregiving stress (Miller et al., 2014) and low socioeconomic status (Levine et al., 2017; Powell et al., 2013) all exhibit a gene expression pattern that is con-ducive to the development of chronic disease. This conserved tran-scriptional response to adversity (CTRA) is characterized by the up-regulation of proinflammatory genes and down-regulation of genes
    Corresponding author at: Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, UCLA, Medical Plaza 300 #3200D, Los Angeles, CA 90095, United States E-mail address: [email protected] (C.C. Boyle).
    involved in antiviral response and antibody synthesis in circulating immune Actinomycin D (Cole, 2009). Elegant work in animal models has shown that early life and social stress induce CTRA upregulation (Chun et al., 2017; Cole et al., 2012; Heidt et al., 2014; Korytář et al., 2016; Powell et al., 2013; Snyder-Mackler et al., 2016; Tung et al., 2012), and there is evidence in humans that acute stress can increase related signaling of the pro-inflammatory transcription factor NF-κB (Bierhaus et al., 2003). Less work has focused on whether positive psychological states, such as eudaimonic well-being, can be similarly leveraged to alter these tran-scriptome dynamics. Here, we use a clinical intervention to interrogate the relationship between changes in eudaimonic well-being and down-regulation of the CTRA in a sample of younger breast cancer survivors.
    Eudaimonic well-being encompasses a sense of purpose and meaning in life, social embeddedness, and the potential for personal growth that may or may not be accompanied by hedonic well-being, or feelings of pleasure, happiness and positive affect (Keyes, 2002; Ryan and Deci, 2001; Ryff, 2018). Longitudinal prospective studies have linked eudaimonic well-being to better physical health, including re-duced morbidity and all-cause mortality (Hill and Turiano, 2014; Steptoe et al., 2015). In several cross-sectional reports, eudaimonic well-being was associated with decreased activation of the CTRA (Cole et al., 2015; Fredrickson et al., 2013, 2015; Kitayama et al., 2016) with consistent evidence that this effect was independent of hedonic well-being and reduced distress (Fredrickson et al., 2013, 2015; Kitayama et al., 2016). Indeed, in a sample of older adults, eudaimonic well-being was a stronger correlate of CTRA gene expression than loneliness or depressive symptoms (Cole et al., 2015), which is particularly notable given well established relationships between loneliness, depression and physical health (Holt-Lunstad et al., 2015; Penninx et al., 2013). Several randomized controlled studies have shown that components of the CTRA can be altered following psychological intervention, in-cluding cognitive behavioral stress management (CBSM) (Antoni et al., 2012, 2016) and mindfulness meditation (Black et al., 2015; Bower et al., 2015; Creswell et al., 2012). These interventions have demon-strated broad, beneficial effects on both psychological distress and eu-daimonic well-being (Bower et al., 2015; Labelle et al., 2015; McGregor et al., 2004), but the extent to which these psychological processes are associated with changes in the CTRA has rarely been examined. One study found that baseline levels of distress were linked to changes in the CTRA following CBSM (Antoni et al., 2012), but eudaimonic well-being was not assessed. There is, however, preliminary evidence that an in-tervention with eudaimonic components decreased CTRA gene ex-pression. Nelson-Coffey et al. (2017) found that participants who were assigned to enact acts of kindness to others, a behavior that promotes and is consistent with eudaimonia (Klein, 2016), exhibited decreases in CTRA gene expression over a 4–5 week period in comparison to parti-cipants randomized to a neutral activity control group. Together, this emerging body of evidence highlights a need for a comprehensive ex-amination of both eudaimonic well-being and distress reduction as potential pathways to change in the CTRA.