Sabine Kunz-Ebrecht

Differences in cortisol awakening response on work days and weekends in women and men from the Whitehall II cohort

It is thought that the salivary cortisol awakening response can serve as a reliable marker of hypothalamic-pituitary-adrenocortical activity. Response magnitude might be influenced by stress, but results of studies on work-related stress have been inconclusive. Non-compliance with the sampling schedule is a potential confounding factor that has rarely been controlled. The objective of the study was to determine whether the cortisol awakening response is greater on a work day than on a weekend day, and whether responses vary with gender and socioeconomic position. Compliance was controlled by excluding participants who reported a delay of more than 10 min between waking up and taking the first saliva sample. Data were collected from 196 men and women aged 47 to 59 years drawn from the Whitehall II cohort of British civil servants, with free salivary cortisol sampled immediately after waking up and 30 min later on 2 days. Data on stress, perceived control and happiness over the remainder of the day, and on sleep quality, time of waking, and health behaviour were also obtained. The awakening response was lower in non-compliant participants than in compliant ones, so non-compliant participants were excluded from further analyses. Salivary cortisol levels on waking did not differ by gender or socioeconomic position, or between work and weekend days. However, the cortisol awakening response (defined as the difference between waking and 30 min later) was greater on work than weekend days (mean increases 10.5 and 3.7 nmol/l, P < 0.001). On the work day, women showed larger increases than men (P = 0.011), but there were no gender differences on the weekend day. Across both days, lower socioeconomic position was associated with a larger cortisol awakening response (P = 0.014). Time of waking up was not related to the cortisol awakening response on either day. Participants rated themselves as more stressed, less in control, and less happy over the remainder of the work than weekend day. These results indicate that the cortisol awakening response occurs on both work and non-work days, but that anticipation of the working day is associated with an enhanced response. Cortisol output over the early part of the day may be particularly sensitive to the influence of chronic stress and its anticipation, especially in women.

Loneliness and neuroendocrine, cardiovascular, and inflammatory stress responses in middle-aged men and women

Loneliness is a psychological experience related to social isolation and perceived lack of companionship, and may be relevant to health risk. The revised UCLA loneliness scale was completed by 240 working men and women aged 47-59 years, and related to affective state and neuroendocrine, cardiovascular, and inflammatory responses. Loneliness scores were not associated with gender, age or socioeconomic position, but were lower in married than single or divorced participants, and were positively related to social isolation, low emotional support, ratings of depression, hopelessness and low self-esteem, and to reported sleep problems. Diastolic blood pressure reactions to acute mental stress were positively correlated with loneliness in women but not men, independently of age, socioeconomic status, smoking, body mass and marital status (p = 0.014). Lonely individuals also displayed significantly greater fibrinogen (p = 0.038) and natural killer cell responses (p = 0.042) to stress, independently of covariates. The cortisol response over the first 30 min following waking was positively associated with loneliness after adjusting for waking cortisol value, sex, socioeconomic status, smoking, time of waking, and body mass (p = 0.046). We conclude that loneliness is a psychological experience with potentially adverse effects on biological stress processes that may be relevant to health.

Work stress, socioeconomic status and neuroendocrine activation over the working day

Socioeconomic status (SES) differences in cardiovascular and metabolic disease risk may be mediated in part by differential activation of neuroendocrine pathways. We have previously found that salivary cortisol levels over the working day are greater in lower than higher SES men, but that cortisol output is greater in higher than lower SES women. This study investigated the role of work stress in generating these patterns, analysing cortisol output in relation to job demands and job control. Participants were 97 men and 84 woman from the Whitehall II cohort, London, UK, recruited from higher and lower grades of employment. Saliva samples were obtained on waking and 30 min later to assess the cortisol waking responses, and at two hourly intervals over a typical working day. Cortisol responses to waking were positively associated with high job demands, but this effect was attenuated by higher SES. In women but not men, cortisol levels over the remainder of the day were elevated in lower SES participants who experienced high job demands, but depressed in lower status women who reported low job demands. Job control did not influence cortisol responses to waking, but in men cortisol levels over the remainder of the day were inversely related to job control. These cortisol differences were independent of age, smoking status and time of waking up. Subjectively, the most stress was reported by higher SES individuals who experienced low job control. We conclude that work stress and SES are related differently to cortisol responses to waking and cortisol output over the day. Job control may partly mediate SES differences in cortisol in men, while job demands are more relevant for women. Analyses of psychobiological pathways must take account of variations in exposure to chronic stressors as well as differences in responsivity to stressors.

Cortisol responses to mild psychological stress are inversely associated with proinflammatory cytokines

Glucocorticoids can down-regulate immune activity, but acute stress has been reported to increase both cortisol and levels of plasma cytokines. We investigated individual differences in cortisol responses and their associations with proinflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), cardiovascular activity, and mental health. Saliva samples and blood were taken from 199 healthy middle-aged participants of the Whitehall II cohort at baseline, immediately after stress and 45 min later. We defined the 40% of participants with the highest cortisol response to stress as the cortisol responder group and 40% with the lowest response as the cortisol non-responder group. Plasma IL-6 was higher and the IL-1ra response to stress was greater in the cortisol non-responder group. The cortisol non-responders showed lower heart rate variability than the cortisol responders. The cortisol responder group experienced more subjective stress during the tasks and reported more impaired mental health than the non-responders. We conclude that individual variations in neuroendocrine stress responsivity may have an impact on proinflammatory cytokines, and that both high and low cortisol stress responsiveness has potentially adverse effects.

Socioeconomic status and stress-related biological responses over the working day.

Objectives The influence of low socioeconomic status on cardiovascular disease may be mediated in part by sustained activation of stress-related autonomic and neuroendocrine processes. We hypothesized that low socioeconomic status would be associated with heightened ambulatory blood pressure and cortisol output over the working day. Methods One hundred eight men and 94 women from the Whitehall II epidemiological cohort participated. Blood pressure and heart rate were monitored every 20 minutes over a working day and evening, and salivary cortisol was sampled on waking up and at 2-hour intervals. Measures were also taken under resting laboratory conditions. Socioeconomic status was indexed by grade of employment. Results Resting blood pressure, heart rate, and cortisol did not differ by grade. Ambulatory systolic pressure was greater in the morning in the lower (128.9 ± 15.7 mm Hg) than the intermediate (122.6 ± 12.5 mm Hg) and higher grades (123.3 ± 12.7 mm Hg) after adjustment for age, sex, smoking, and alcohol intake (p = .019). Heart rate was also raised in the morning in the lower grade participants. Differences in morning systolic pressure and heart rate were independent of concurrent physical activity. Cortisol concentration was greater in lower than higher grade men (9.54 ± 4.1 vs. 7.38 ± 2.8 nmol/liter, p = .008) but was more elevated in higher than lower grade women (7.84 ± 2.5 vs. 6.35 ± 1.9 nmol/liter, p = .014). Differences remained significant after adjustment for age, time of awakening, smoking, and alcohol intake. Conclusions Socioeconomic differences in blood pressure and cortisol may reflect stress-related activation of biological pathways that contribute to variations in disease risk.

Inflammatory cytokines, socioeconomic status, and acute stress responsivity

Socioeconomic status is a major determinant of coronary heart disease (CHD). Proinflammatory cytokines are implicated in the etiology of CHD, and are also sensitive to emotional stress. We hypothesised that concentration of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 receptor antagonist (IL-1Ra) would be inversely related to socioeconomic status, and that cytokine responses to stress would be associated with SES. One hundred and twenty-five middle-aged men and 105 women from the Whitehall II epidemiological cohort were tested, and socioeconomic status was indexed by grade of employment, with participants divided into high, intermediate, and low status groups. Plasma concentrations at rest of TNF-alpha, IL-1Ra, and IL-6 (women only) were associated with socioeconomic status, with lower levels in the high status group, but the effect was non-linear. There was no relationship between socioeconomic status and cytokine responses to stress, but sex differences were observed, with men showing greater TNF-alpha, and women greater IL-6 and IL-1Ra increases. The role of inflammatory cytokines in mediating psychosocial influences on CHD is discussed.

Lack of association between depressive symptoms and markers of immune and vascular inflammation in middle-aged men and women

BACKGROUND Disturbed immune activity and vascular inflammation are associated both with clinical depression and coronary atherogenesis, and may constitute a mechanism through which depression contributes to coronary heart disease. If this is the case, then non-clinical depressive symptoms and psychological distress should be associated with immune activation and vascular inflammation. We tested this hypothesis in a healthy middle-aged sample. METHOD Measures of depressive symptoms and hopelessness were obtained from 226 volunteers (122 men, 104 women) aged 47-59 years, drawn from the Whitehall II epidemiological cohort. C-reactive protein, fibrinogen, plasma interleukin-6, tumour necrosis factor alpha, interleukin-1 receptor antagonist, and T- and B-lymphocyte, and natural killer cells numbers and percentages were assessed. RESULTS There were no associations between measures of depressive symptoms or hopelessness and markers of immune activation or inflammatory response. CONCLUSIONS Factors such as the measures of depressive symptoms, the choice of inflammatory and immune indices, and sample size, are unlikely to be responsible for these null effects. Associations may be confined to clinically depressed or older age populations, but there are problems of confounding by co-morbidity and health compromising behaviours in this literature. We conclude that disturbances of immune function and inflammatory processes are unlikely to be primarily responsible for the associations between depressive symptoms and coronary heart disease described in the literature, and that other pathways are involved.

Changes in Financial Strain Over Three Years, Ambulatory Blood Pressure, and Cortisol Responses to Awakening

Objective: Chronic psychosocial stress has been associated cross-sectionally with ambulatory blood pressure and with salivary cortisol, but there have been few longitudinal studies of the effects of changes in chronic stress. We assessed the influence of changes in financial strain on ambulatory blood pressure and salivary cortisol. Methods: Data were analyzed from 160 men and women age 47 to 59 years at the first assessment (T1) who repeated ambulatory monitoring 3 years later (T2). We analyzed change in financial strain as a continuous variable, and specifically compared people who did and did not report an improvement in financial strain. Results: Change in financial strain was associated with change in ambulatory systolic pressure after controlling for T1 ambulatory systolic pressure, gender, socioeconomic position, age, smoking, body mass index, and T1 financial strain (p = .041). Systolic pressure at T2 was lower in the improved financial strain (121.7 ± 11.2 mm Hg) than in the worse/no change group (125.5 ± 11.5 mm Hg; p = .029). The corresponding diastolic pressures averaged 78.5 ± 7.1 mm Hg and 80.7 ± 7.9 mm Hg, respectively (p = .061). The cortisol awakening response (difference between waking and 30 minutes later) was lower (p = .048) in men who reported improved financial strain, controlling for T1 cortisol response, socioeconomic position, age, smoking, time of waking, and T1 financial strain. There were no differences in the slope of cortisol decline over the day or in evening values. Conclusion: These longitudinal data extend cross-sectional findings in showing associations between favorable changes in chronic stress and reduced cardiovascular and neuroendocrine activation in everyday life. CAR = cortisol awakening response; BMI = body mass index; SEP = socioeconomic position; CHD = coronary heart disease; CI = confidence interval.

Dispositional optimism and health behaviour in community-dwelling older people: associations with healthy ageing.

OBJECTIVE Dispositional optimism measured with the Life Orientation Test has been associated with a variety of health outcomes. We assessed whether optimism was related to indices of healthy ageing, and if effects were mediated through health behaviours. METHOD A community sample of 128 men and women aged 65 to 80 years was recruited from general practice lists. Optimism and health behaviours were assessed by questionnaire, and healthy ageing indexed by physical health summary scores from the Short Form 36, and by self-rated health. RESULTS Optimism was associated with not smoking, moderate alcohol consumption, brisk walking, and vigorous physical activities (women only), independently of socio-demographic factors and clinical condition. Physical health status was associated with optimism, independently of socio-demographic factors, clinical condition, negative affectivity, and body mass. This effect was attenuated when health behaviours were taken into account. Self-rated health was also positively related to optimism, and this association was not mediated by health behaviours. Neither the optimism nor pessimism subscales of the Life Orientation Test showed as consistent effects as the full scale. CONCLUSIONS We conclude that dispositional optimism is associated with healthy ageing. The relationship between optimism and healthy ageing was only partly mediated by the health behaviours assessed in this sample.

Influence of socioeconomic status and job control on plasma fibrinogen responses to acute mental stress.

Objective An elevation in plasma fibrinogen may be one of the pathways through which low socioeconomic status increases cardiovascular disease risk. This study assessed the influence of socioeconomic status, job control, and social isolation on fibrinogen responses to acute stress. Methods The study was conducted with 125 white men and 96 white women aged 47 to 58 years, drawn from the Whitehall II cohort. Socioeconomic status was indexed by grade of employment, with 82 high, 75 intermediate, and 64 low grade participants. Plasma fibrinogen and hematocrit were assessed at baseline, immediately after performance of color-word and mirror tracing tasks, and 45 minutes later. Results Plasma fibrinogen increased from baseline to stress (from 2.85 ± 0.57 to 2.92 ± 0.58 g/liter), remaining elevated 45 minutes after stress (2.89 ± 0.58 g/liter, p < .001). Fibrinogen concentration was greater in the low than in the high or intermediate employment grade groups, independently of sex, age, body mass index, smoking status, and hematocrit. Fibrinogen responses to acute stress did not differ across employment grades. Women had higher fibrinogen levels than men, but this pattern was abolished in women taking hormone replacement therapy. Men experiencing low job control showed greater fibrinogen responses to acute stress than did those with high job control (p = .003). Fibrinogen levels were greater in socially isolated individuals, but social isolation did not affect responses to acute stress. Conclusions Socioeconomic status and acute stress had independent effects on the plasma fibrinogen level. Low job control may influence cardiovascular disease risk in men partly through provoking greater fibrinogen stress responses.