Natalie Owen

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.

Acute mental stress elicits delayed increases in circulating inflammatory cytokine levels

The influence of acute mental stress on cardiovascular responses and concentrations of inflammatory cytokines up to 2 h later was assessed in 12 subjects exposed to stress and in eight control subjects. Beat-by-beat recordings of finger blood pressure and heart rate were made at rest and during two behavioural tasks (colour-word interference and mirror tracing). Blood was drawn after adaptation and at 45 min and 2 h after the tasks, and assayed for interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 receptor antagonist (IL-1Ra), C-reactive protein (CRP) and haematocrit. Saliva was sampled periodically and assayed for free cortisol. The tasks were rated as stressful by the participants. The stress group showed significant increases in systolic and diastolic blood pressure (mean rises of 16.4+/-12.3 and 12.6+/-6.9 mmHg respectively) and heart rate (5.39+/-5.3 beats/min); these values returned to baseline during the recovery period. The IL-6 concentration was increased by 56% at 2 h after the tasks (P<0.05), while IL-1Ra was increased by 12.3% (P<0.01). No changes in cardiovascular variables or cytokine concentrations were observed in the control subjects, and haematocrit did not change. The magnitude of blood pressure responses during tasks was correlated positively with the IL-6 concentration after 45 min (r=0.70, P<0.05), and with the IL-1Ra concentration after 2 h (r=0.63, P<0.05). Increases in TNF-alpha after 2 h were correlated with heart rate responses to tasks (r=0.66, P<0.05). Associations between IL-6 and IL-1Ra concentrations were also recorded. This study indicates that inflammatory cytokines respond to acute mental stress in humans with delayed increases, and suggest that individual differences in cytokine responses are associated with sympathetic reactivity.

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.

Socioeconomic status, C-reactive protein, immune factors, and responses to acute mental stress

Low socioeconomic status (SES) is associated with increased risk of coronary heart disease and immune-related disorders. We hypothesised that SES would be inversely associated with the acute phase reactant C-reactive protein (CRP) and with circulating lymphocyte levels, and that lymphocyte responses to acute psychological stress would also vary with SES. CRP was obtained from 226, and lymphocyte counts from 127 healthy volunteers from the Whitehall II cohort, and SES was defined primarily by grade of employment. CRP concentration was greater in lower compared with higher SES participants (1.18+/-0.75 vs. 0.75+/-0.8 mg/l,p=.002) independently of sex, age, body mass, waist/hip ratio, smoking, alcohol, and season of the year. Similar differences were evident when SES was defined by income and educational attainment. Higher SES was also associated with lower total lymphocyte (p=.023), T-lymphocyte (p=.024) and natural killer (NK) cell counts (p=.006). Total, T- and B-lymphocyte, and NK cell counts increased with stress, but immune stress reactivity did not vary with SES. Post-stress recovery was delayed in women compared with men. The results suggest that moderate inflammation and immune activation may be processes through which lower SES increases disease risk.

Circulating Human Heat Shock Protein 60 in the Plasma of British Civil Servants Relationship to Physiological and Psychosocial Stress

Background—The Whitehall cohort studies (I and II) of British civil servants have identified sociodemographic, psychosocial, and biological risk factors for coronary heart disease (CHD). To identify mechanisms responsible for susceptibility to CHD, specific biological markers of stress are increasingly being measured. One marker linked to susceptibility to CHD is heat shock protein (Hsp) 60. Methods and Results—Blood was taken from 229 civil servants (126 men and 103 women) in the Whitehall II cohort drawn equally from the range of employment grades. Plasma was assayed for levels of Hsp60, tumor necrosis factor &agr; (TNF&agr;), C-reactive protein, von Willebrand factor, high density lipoprotein (HDL), total cholesterol, and total/HDL ratio. Psychosocial measures included socioeconomic status, psychological distress, and social isolation. The majority of the participants had Hsp60 in their plasma, and ≈20% had >1000 ng/mL of this protein (a concentration likely to induce biological effects). A positive association between plasma Hsp60 and TNF&agr; and a negative association with von Willebrand factor was found. There was also a significant association between elevated Hsp60 levels, low socioeconomic status, and social isolation, together with an association with psychological distress in women. Conclusions—The majority of participants exhibited Hsp60 in their plasma, and there was evidence of an association between levels of this stress protein and the proinflammatory cytokine, TNF&agr;, and with various psychosocial measures.

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.

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.

Panic disorder with agoraphobia associated with dizziness: characteristic symptoms and psychosocial sequelae

The aim of this study was to assess the prevalence of symptoms of panic disorder in a representative community sample of people with dizziness and to compare the profile of those whose panic was consistently linked to attacks of dizziness with those in whom dizziness was just one of many, variable somatic symptoms of panic. Validated questionnaires assessing physical and psychological symptoms, occupational disability, and handicap were administered to 128 people reporting dizziness in an epidemiological survey. Nearly two thirds of the sample reported having panic attacks, and one in four met key criteria for panic disorder. People whose panic symptoms were consistently associated with dizziness reported higher rates of vertigo than those with panic unrelated to dizziness, and higher rates of fainting, agoraphobic behavior, and occupational disability than either comparison group. Explanation of perceptual-motor triggers for disorientation may increase the predictability of attacks, thus reducing vulnerability to dizziness-provoked panic.

Natural killer cell and proinflammatory cytokine responses to mental stress: associations with heart rate and heart rate variability

Associations between natural killer (NK) cell, proinflammatory cytokine stress responsivity, and cardiac autonomic responses (indexed by heart rate and heart rate variability) were assessed in 211 middle-aged men and women. Blood was drawn at baseline, immediately following color-word interference and mirror tracing tasks for the assessment of NK cell numbers, and 45 min post-stress for assessing plasma interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha) responses. Heart rate variability was measured as the root mean square of successive differences (RMSSD) in R-R intervals. Increases in NK cell counts following stress were positively associated with heart rate responses independently of age, sex, socioeconomic status, smoking, and change in hematocrit. Heart rate 45 min post-stress was positively associated with plasma IL-6 post-stress, and with TNFalpha changes from baseline, independently of covariates. No relationship between immune responses and heart rate variability was observed. We conclude that individual differences in sympathetically-driven cardiac stress responses are associated with NK and proinflammatory cytokine responses to psychological stress.