Neuroendocrine and Inflammatory Factors Associated with Positive Affect in Healthy Men and Women: The Whitehall II Study

Abstract

Positive affective states are associated with favorable health outcomes, but the underlying mechanisms are poorly understood. The authors assessed associations between positive affect, cortisol sampled over the day, and inflammatory markers (C-reactive protein and interleukin-6) among 2,873 healthy members of the Whitehall II study. Data for this study were collected in 2002-2004 in London, United Kingdom. Saliva free cortisol was assessed on waking, 30 minutes later, and four times over the day and evening. Positive affect was indexed by aggregating ecological momentary assessments of positive mood over the day. Salivary cortisol averaged over the day was inversely associated with positive affect after controlling for age, gender, income, ethnicity, body mass index, waist/hip ratio, smoking, paid employment, time of waking in the morning, and depression (p ¼ 0.003). There was no association with cortisol responses to waking. The adjusted odds of C-reactive protein 3.00 mg/liter was 1.89 (95% confidence interval: 1.08, 3.31) in low-compared with high-positive-affect women, and plasma interleukin-6 was also inversely related to positive affect in women (p ¼ 0.016). Neither inflammatory marker was related to positive affect in men. These results confirm findings from smaller studies relating cortisol with positive affect while suggesting that in women, positive affect is associated with reduced levels of inflammatory markers. adrenal cortex hormones; affect; C-reactive protein; happiness; interleukin-6 Abbreviations: CES-D, Center for Epidemiologic Studies Depression; CRP, C-reactive protein; IL-6, interleukin-6; SD, standard deviation.Positive affective states and positive well-being are associated with reduced risk of physical disease and prolonged healthy life expectancy (1). Associations have been described between positive psychological states and greater longevity, reduced risk of death due to stroke and coronary heart disease, and delayed onset of disability and hypertension (2-8), stimulating the search for mediating biologic and behavioral pathways.Direct associations with neuroendocrine, inflammatory, and immune processes may be present. Positive affect has been shown to predict reduced risk of upper respiratory infectious illness following experimentally administered virus (9) and greater antibody responses to hepatitis B vaccination (10). In an earlier study with a subsample from the Whitehall II cohort (n ¼ 216), we assessed positive affect by aggregating ecological momentary assessments of positive affect over a working day and evening (11). Positive affect was associated with lower salivary free cortisol over the working day independently of age, gender, socioeconomic status, smoking, body mass index, and negative affect. Similar findings were observed over a weekend day, and effects were replicated at 3-year follow-up (12). Positive affect was also related to reduced fibrinogen responses to acute mental stress. These cortisol differences have been observed in Correspondence to Dr.

Positive emotional style and subjective, cardiovascular and cortisol responses to acute laboratory stress

“…Psychobiological pathways linking positive emotions and health outcomes are not yet well understood but may include variations in the activation and/or control of neuroendocrine, autonomic, immune and inflammatory pathways. Positive emotional dispositions have been associated with enhanced parasympathetic nervous system control in CHD patients (Bhattacharyya et al, 2008), increased antibody response to a vaccine (Marsland et al, 2006), and reduced daily cortisol output (Polk et al, 2005;Steptoe et al, 2008). Positive dispositions could influence cognitive appraisal of potentially 'stressful' daily events, leading to lower threat perceptions and reduced activation of the autonomic nervous system and hypothalamic-pituitary (HPA) axis (Lazarus and Folkman, 1984).…”

“…Evidence from naturalistic studies indicates that positive affect over several days is inversely related to daily cortisol output, independent of negative affect (Polk et al, 2005;Steptoe et al, 2005Steptoe et al, , 2008. However, findings are not entirely consistent; in a study measuring cortisol and current mood amongst 556 women over five days, Jacobs et al (2007) found that only negative affect was independently associated with cortisol.…”

Post awakening salivary cortisol secretion and trait well-being: The importance of sample timing accuracy

“…These data contribute to evidence that, unlike for post awakening AUCg, there may be no reliable association between the CAR and TWB in healthy populations (e.g. Garcia-Banda et al, 2014;Steptoe et al, 2008) . Indeed in their meta-analysis of PACS and psychosocial factors Chida and Steptoe noted that the relationship between the dynamic of the CAR (unlike for the AUCg) and general life stress was not statistically significant when only studies with high methodological quality were included in the analysis (Chida & Steptoe, 2009).…”

“…For instance, opposite or null relationships have often been reported (e.g. Evans et al, 2007;Juster et al, 2011;Lovell et al, 2011;Stalder et al, 2010b;Steptoe et al, 2007;Steptoe et al, 2008;Thorn et al, 2006;Wahbeh et al, 2008;Wuest et al, 2000a). It is now recognized as essential to distinguish the CAR and AUCg measures of PACS.…”

Happiness and its molecular fingerprints

“…Steptoe et al 2008;Tuck et al 2016). But because low-grade systemic inflammation is related to numerous other exposures and phenotypes, the assessment of its causal role in well-being is hampered by potential confounding.…”