Negative affectivity predicts decreased pain tolerance during low-grade inflammation in healthy women.

INTRODUCTION: Experimental animal studies provided evidence for a synergistic effect of immunological and psychological stressors on subsequent sickness behaviours. Up to now, little corroborating evidence for such synergy exists for humans, in whom it may provide a mechanism leading to the expression of functional somatic symptoms. The aim of the present study was to determine an interaction between stress(-vulnerability) and an immunological activation on experimental pain sensitivity, i.e., pressure pain threshold and tolerance in healthy humans. METHODS: In healthy female participants (n=25, mean age 22.3 years), negative affectivity (NA) and experienced stress were assessed by questionnaire before receiving a Salmonella typhi vaccine or saline control in a randomized blinded cross-over design. Pressure pain threshold was assessed at the lower back and calves and pain tolerance was assessed at the thumbnail, before and six hours after each injection. RESULTS: Vaccination induced leukocytosis (+100%) and increased serum IL-6 (+670%). NA predicted decreased pain tolerance after vaccination (ß=-.57, p=.007), but not after placebo (ß=.25, p=.26). Post-hoc analyses also demonstrated an association with administration order. DISCUSSION: NA moderated the effects of inflammation on pain tolerance. This finding is consistent with a synergistic model whereby inflammation may lower the threshold for pain reporting in individuals with increased vulnerability for somatic symptom reporting.

Young adults' reactions to infant crying.

An infant's optimal development is determined to a great extent by the adequate and sensitive responses of the caregiver. The adequacy and sensitivity of a reaction to an infant in distress (i.e. crying) will partly depend on the causal attributions of the crying and on the individual's sympathy for the infant. Being female, prior caring experiences, and multiparity have shown to be linked to more sympathetic, tolerant and less hostile emotional responses to crying. However, little is known about other factors explaining inexperienced future caregivers' reactions to infant crying. The present paper's goal is to shed more light on the subject by looking at how personality factors, caregiving interest, sex, promptness of the reaction, and gender identity are related to emotional reactions and causal attributions to crying in a population of young adults without children. One hundred and ninety-one childless university students participated (126 females; ages 18-35 years). The participants completed questionnaires on personality, gender identity and caregiving interest, and listened to an audio sample of an infant crying, reporting their emotions and their causal attributions to the crying. The results showed that experiencing anger was associated with more child-blaming attributions to the crying, while quickness of response and feelings of sympathy predicted more child-oriented attributions. The latter was stronger in males. Explicit care interest decreased child-blaming causal attributions more for men than for the women. Interestingly, solely in the females' personality factors neuroticism and conscientiousness played a role in child blaming attributions together with anger. These findings suggest that the motives that young adults attribute to a crying infant depend in males on the emotions triggered by the crying, responsiveness and care interest. While in females, emotions, responsiveness and personality affect the causal attribution to the crying. Future research is needed in order to determine whether these attributions are also linked to young adults' actual behaviour towards a crying infant.

[Questioning the mechanism behind slow breathing and heart coherence training]. / Vraagtekens bij het werkingsmechanisme van slow-breathing en hartcoherentietraining.

BACKGROUND: Slow breathing and heart coherence training are being offered increasingly as treatments for anxiety, depression and stress-related mental and somatic complaints. Both of these interventions are aimed at influencing (i.e. increasing or optimising) heart rate variability and the mechanism involved is described in terms such as heart coherence, resonance breathing and heart-brain communication. AIM: To find out whether treatment effects are indeed based on the optimisation of heart rate variability. METHOD: Our literature search focused on 1) the assumption that poor mental health is definitely linked to deviant heart rate variability, and 2) the assumption that optimising heart rate variability leads specifically to a reduction of complaints and symptoms. RESULTS: There is insufficient evidence to support these two assumptions. CONCLUSION: Slow breathing and heart coherence training probably achieve their effects as a result of non-specific psychological mechanisms.

[Work-stress and cortisol; measurements and results]. / Werkstress en cortisol; meetfilosofie en bevindingen.

Physiological measurements of stress are believed to help with the 'objectivation' of the rather subjective phenomenon called 'stress'. Because there are only moderate interpersonal correlations between the subjective experience of work-stress and physiological stress measurements, the latter are useful mainly for comparing groups with high stress and groups with low stress and not as a diagnostic tool at individual level. Physiological measurements have added value because they quantify the strain that stress exerts on the body, which ultimately determines what effect stress has on health. In addition, physiological measurements on persons with stress-related symptoms such as burn-out can help us understand the nature of the dysregulation of the stress-regulatory system which occurs in the persons with these types of symptoms. The comparison of high-stress groups and low-stress groups on the basis of various cortisol parameters has produced rather inconsistent results. This seems to be due not only to the unreliability of the measurements but also to the fact that cortisol is apparently a rather inaccurate reflection of the stress-regulatory system in the brain. Research into the changes that occur over time in the cortisol-regulatory system resulting from chronic work-stress and into the health-relevance of various cortisol parameters is essential if progress is to be achieved in this area.

Migraine patients as trainers of their fellow patients in non-pharmacological preventive attack management: short-term effects of a randomized controlled trial.

In conformity with current views on patient empowerment, we designed and evaluated the effects of home-based behavioural training (BT) provided by lay trainers with migraine to small groups of fellow patients. The primary aims of BT were to reduce attack frequency and increase perceived control over and self-confidence in attack prevention. In a randomized controlled trial the BT group (n = 51) was compared with a waitlist-control group (WLC), receiving usual care (n = 57). BT produced a minor (-21%) short-term effect on attack frequency and clinically significant improvement in 35% of the participants. Covariance analysis showed a non-significant trend (P = 0.07) compared with WLC. However, patients' perceived control over migraine attacks and self-confidence in attack prevention increased significantly with large effect sizes. Patients with high baseline attack frequency might benefit more from BT than those with low attack frequency. In conclusion, lay trainers with migraine strengthened fellow patients' perceived control, but did not induce a significant immediate improvement in attack frequency.

Emotion regulation predicts change of perceived health in patients with rheumatoid arthritis.

OBJECTIVES: To examine whether emotion regulation predicts change of perceived health in patients with rheumatoid arthritis (RA). METHODS: Sixty six patients (44 female, 22 male; mean (SD) age 57.7 (11.6) years) participated in a prospective study. Hierarchical regression analysis was used to predict change of perceived health between study entry and follow up (1(1/2) years later) from the emotion regulation styles ambiguity, control, orientation, and expression at study entry. RESULTS: Valuing and intensely experiencing emotions (emotional orientation) predicted a decrease of positive affect. Difficulty recognising and expressing emotions (ambiguity) predicted an increase of perceived disease activity. Emotion regulation showed no associations with change of negative affect and social and physical functioning. CONCLUSIONS: Two styles of emotion regulation were shown to have a significant though modest role in the prediction of perceived health change in patients with RA. This suggests that the monitoring of emotion regulation may help to identify patients who are at risk for a reduction of perceived health. If our findings were confirmed by experimental research, improving emotion regulation skills might favourably affect perceived health.

Neuroendocrine-immune relationships between emotion regulation and health in patients with rheumatoid arthritis.

OBJECTIVES: Emotion regulation is hypothesized to be related to health through neuroendocrine-immune changes. This study examined the role of the neuroendocrine variables 24-h urinary cortisol and noradrenaline, and the immune variable serum interleukin 6 as mediators between emotion regulation styles and health (perceived health and disease activity: erythrocyte sedimentation rate (ESR) and Thompson joint score). METHODS: Sixty patients with rheumatoid arthritis (mean age 59.0+/-11.2 yr; 38 female) participated. RESULTS: Emotion regulation was not associated with immune functioning or disease activity, but it was somewhat related to neuroendocrine functioning: one of the emotion regulation styles, ambiguity, was related to noradrenaline in women (r = 0.39) but not in men. The indicators of neuroendocrine functioning (cortisol and noradrenaline) were correlated (r = 0.40), as were indicators of immune functioning (interleukin 6) and inflammatory activity (ESR; r = 0.53), but analyses did not indicate a role of these physiological variables in mediating between emotion regulation and health: neuroendocrine variables were not related to interleukin 6 or ESR, and none of the physiological parameters was correlated with joint score or perceived health. CONCLUSIONS: To examine whether the proposed mediational processes apply to individual patients, a longitudinal within-subjects design is needed. In our cross-sectional study, emotion regulation was somewhat related to neuroendocrine functioning, but our study did not uncover a potential mediational role of cortisol, noradrenaline or interleukin 6 in the relationship between emotion regulation and health in rheumatoid arthritis.

Perioperative microembolism is not associated with cognitive outcome three months after carotid endarterectomy.

OBJECTIVE: To investigate the association between perioperative microembolism and cognitive outcome 3 months after carotid endarterectomy (CEA). DESIGN: Prospective study. MATERIALS AND METHODS: Patients were tested 1 day before and 3 months after surgery with neuropsychological tests measuring a wide range of cognitive functions. Number of microemboli was monitored with transcranial Doppler ultrasonography in 58 patients during the operation and in a random subgroup of 27 patients directly following the procedure. RESULTS: Forty patients (69%) had intraoperative embolism, varying from 1 to 33 isolated microemboli and/or 1 to 11 embolic showers. Postoperative emboli were present in 22 of the 27 patients (81%), ranging from 1 to 142 isolated microemboli. More than 10 microemboli (including showers) were detected in 13 patients (22%) intraoperatively and in 6 patients (22%) postoperatively. Twenty-two patients (38%) showed deterioration in three or more cognitive function variables at 3 months. There were no significant associations between any cognitive change or deterioration score and presence or number of intraoperative and/or postoperative emboli. CONCLUSIONS: The degree of microembolism during and immediately following CEA is generally small and seems to be of no significance with respect to postoperative cognitive functioning. Future research should include a larger group of patients to allow reliable subgroup analysis.

Elevated sympathetic nervous system activity in patients with recently diagnosed rheumatoid arthritis with active disease.

OBJECTIVE: To investigate sympathetic (SNS) and parasympathetic (PNS) nervous system activity in patients with recently diagnosed rheumatoid arthritis (RA), and to analyze the association between activity of these systems and disease activity, and complaints that frequently occur in RA, viz., pain, fatigue, negative mood, and stiffness. METHODS: To assess sympathetic and parasympathetic nervous activity, the Pre-Ejection-Period (PEP) and Respiratory Sinus arrhythmia (RSA) were measured on two consecutive nights in a real-life environment in 25 patients with RA [19 female (f), 6 male (m), mean age 55.2 years) and 28 healthy controls (20f, 8m, mean age 55.8 years]. RESULTS: Patients showed a significantly shorter PEP (reflecting elevated SNS activity) compared to healthy controls, an effect that was most pronounced in those with active disease. RSA and the heart period did not differ between patients and healthy controls. The heart period was significantly associated with stiffness, but neither PEP nor RSA were associated with pain, fatigue, mood, or stiffness. CONCLUSION: Our study showed that cardiac sympathetic nervous system activity is elevated in RA, whereas cardiac parasympathetic activity remains at a normal level. Our results suggest that inflammatory stress rather than the common symptoms of RA challenge the SNS.

Experimentally challenged reactivity of the hypothalamic pituitary adrenal axis in patients with recently diagnosed rheumatoid arthritis.

OBJECTIVE: There is evidence that the hypothalamic pituitary adrenal (HPA) axis is subresponsive in patients with rheumatoid arthritis (RA). We assessed HPA axis responses to experimental stressors mimicking daily life challenges in patients with RA to determine whether HPA axis activity is associated with Th1 and Th2 activity. METHODS: ACTH and cortisol responses in reaction to the succession of a bicycle ergometer task, a cold pressor task, and a computerized Stroop Color-Word interference test, as well as basal Th1 and Th2 cell activity, were assessed in 29 patients (21 female, 8 male) with recently diagnosed RA (mean disease duration 29 wks, range 5-69), mean age 55.7 years, none receiving glucocorticoid treatment, and 30 (20 female, 10 male) healthy age and sex matched controls (mean age 54.1 yrs). RESULTS: Mean ACTH and cortisol levels did not differ between the groups (p > 0.10). Patients tended to have a less pronounced ACTH response (F2.50 = 2.7, p = 0.08) and had a significantly smaller cortisol response (P F2.50 = 6.1, p < 0.01) than healthy controls in reaction to the stressors. This difference in cortisol response was reduced, but remained significant when ACTH responsiveness was accounted for by entering it as a covariate (P F2.49 = 3.7, p = 0.03). ACTH and cortisol levels and responses were not associated (all p > 0.19) with basal interferon-gamma and interleukin 4 as reflections of Th1 and Th2 cell activity, respectively. HPA axis activity was not linked to current disease activity. CONCLUSION: Our findings show reduced HPA axis responsiveness in RA patients with recent diagnosis receiving longterm medication that is suggested to be located both at a hypothalamic/pituitary and at an adrenal level. It appears that common HPA axis activity accomplishes low amounts of cortisol release, which makes it difficult to determine an influence of endogenous cortisol changes on the Th1/Th2 balance.

Job strain and risk indicators for cardiovascular disease in young female nurses.

This study examined the possible effects of job demands, decision latitude, and job-related social support on risk indicators for cardiovascular disease (CVD) in 165 female nurses. Job strain was measured with the Job Content Questionnaire; CVD risk was measured with insulin, total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fibrinogen, tissue-type plasminogen activator (tPA) antigen, tPA activity, plasminogen activator inhibitor-1 antigen, and blood pressure. Multivariate analysis of covariance and regression analyses revealed no effects of either job strain or social support on these risk indicators. All risk indicators deteriorated with age and body mass index. Oral contraceptive use improved fibrinolytic potential and increased HDL-C but had adverse effects on TG levels. Results suggest that in healthy young women job strain is not associated with an unfavorable metabolic or fibrinolytic risk profile.

Effects of work stress on ambulatory blood pressure, heart rate, and heart rate variability.

Work stress has repeatedly been associated with an increased risk for cardiovascular disease. This study tested whether this relationship could be explained by exaggerated cardiovascular reactivity to work or impaired recovery in leisure time. Vagal tone was assessed as a possible determinant of these work stress effects. Participants included 109 male white-collar workers (age, 47.2+/-5. 3) who were monitored on 2 workdays and 1 nonworkday for ambulatory blood pressure, heart rate, and heart rate variability. Chronic work stress was defined according to Siegrist's model as (1) high imbalance, a combination of high effort and low reward at work, or (2) high overcommitment, an exhaustive work-related coping style indexing the inability to unwind. All findings were adjusted for possible differences in posture and physical activity between the work stress groups. High imbalance was associated with a higher heart rate during work and directly after work, a higher systolic blood pressure during work and leisure time, and a lower 24-hour vagal tone on all 3 measurement days. Overcommitment was not associated with an unfavorable ambulatory profile. Logistic regression analysis revealed that heart rate [odds ratio 1-SD increase 1.95 (95% CI, 1.02 to 3.77)] and vagal tone [odds ratio 1-SD decrease 2.67 (95% CI, 1.24 to 5.75)] were independently associated with incident mild hypertension. Surprisingly, the values during sleep were more predictive for mild hypertension than the values during work. The results from the present study suggest that the detrimental effects of work stress are partly mediated by increased heart rate reactivity to a stressful workday, an increase in systolic blood pressure level, and lower vagal tone.

Genetics of testosterone and the aggression-hostility-anger (AHA) syndrome: a study of middle-aged male twins.

The aim of this study was to determine the genetic contribution to the variation in testosterone and the aggression-hostility-anger (AHA) syndrome in middle-aged twins. Moreover, the relation between testosterone and this syndrome, and possible common genetic mechanisms were investigated. Towards this end, blood samples were collected at two time points; the AHA syndrome was measured using three questionnaires: the Buss-Durkee Hostility Inventory with seven subscales, the Jenkins Activity Survey and the Spielberger State-Trait Anger Scale. The results showed substantial heritabilities for testosterone (approximately 60%) and moderate to fair heritabilities for the nine measures of the AHA syndrome (23-53%). The best fitting model for testosterone at two time points included a small age component and additive genetic and unique environmental factors, while a multivariate analysis of the nine AHA subscales resulted in an independent pathway model with two common additive genetic and two common unique environmental factors. No correlation between the common genetic factor influencing testosterone and the AHA subscales was found. We did, however, detect a negative correlation between the common environmental factor underlying testosterone and both common environmental factors influencing the nine AHA subscales, which may reflect a tendency for testosterone levels to rise and hostility to drop (or vice versa) after repeatedly experiencing success (or failure).

Work stress and metabolic and hemostatic risk factors.

OBJECTIVE: A high level of work stress has been associated with cardiovascular disease. However, the pathophysiological mechanisms underlying this association remain unclear. This study examined the effect of work stress on a cluster of metabolic and hemostatic risk factors. METHODS: Blood was collected three times, on the first, third, and fifth day of a work week, from 124 middle-aged, white-collar workers. Metabolic measures were insulin, glucose, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and total cholesterol. Hemostatic measures were fibrinogen, tissue-type plasminogen activator activity, tissue-type plasminogen activator antigen, and type 1 plasminogen activator inhibitor antigen. Chronic work stress was defined according to Siegrist's model as 1) a combination of high effort and low reward at work (effort-reward imbalance) or 2) high overcommitment (an exhaustive work-related coping style). RESULTS: Overcommitment, but not imbalance or the imbalance-overcommitment interaction, was associated with an impaired fibrinolytic system, as reflected in decreased tissue-type plasminogen activator activity levels and increased type 1 plasminogen activator inhibitor antigen levels on all three measurement occasions. After controlling for body mass index, total cholesterol, triglycerides, high-density lipoprotein/low-density lipoprotein cholesterol ratio, glucose, and insulin, the relation between overcom-mitment and the fibrinolytic factors was attenuated but remained significant. CONCLUSIONS: The results suggest that individuals with an exhaustive coping style at work have an impaired fibrinolytic capacity that is possibly due to the effects of chronic stress on insulin resistance.

Dissecting the genetic architecture of lipids, lipoproteins, and apolipoproteins: lessons from twin studies.

We review the ways in which twin studies have been used to investigate the genetic architecture of lipids, lipoproteins, and apolipoproteins. We focus on the age dependency of genetic effects and the importance of pleiotropy for the lipid system. Finally, consequences are discussed of age dependency and pleiotropy for the design and power of twin studies aimed at detecting the actual quantitative trait loci (QTLs) involved. It is concluded that twin studies have played an important role and will remain highly valuable for the elucidation of the genetic architecture of lipids, lipoproteins, and apolipoproteins. Twins can efficiently be used to identify the location and function of QTLs. Taking account of pleiotropy and age-dependent gene expression in study design and data analysis will improve the power and efficiency to find these QTLs for components of the lipid system.

Light and diurnal cycle affect human heart rate: possible role for the circadian pacemaker.

Humans and animals demonstrate diurnal rhythms in physiology and behavior, which are generated by the circadian pacemaker, located in the supra-chiasmatic nucleus (SCN). The endogenous diurnal rhythm of the SCN is synchronized to the diurnal cycle most effectively by light. However, light also influences the SCN and its output instantaneously, as is demonstrated for the immediate effects of light on SCN neuronal firing frequency and on the output of the SCN to the pineal, inhibiting melatonin secretion. In addition to this, the circadian pacemaker modulates neuronally also other organs such as the adrenal. Therefore, the authors investigated the effect of this light input to the SCN on human heart rate, using light at different phases of the day-night cycle and light of different intensities. Resting heart rate (HR) was measured in volunteers between 20 and 40 years of age during supine, awake, resting conditions, and after 2 hours of fasting. In Experiment 1, HR was measured at different times over the day-night cycle at 0 lux and at indoor light. In Experiment 2, HR was measured at different times over the day-night cycle at controlled light intensities of 0 lux, 100 lux, and 800 lux. The authors demonstrate a clear diurnal rhythm in resting HR in complete darkness, similar to that measured under constant routine conditions. Second, it is demonstrated that light increases resting HR depending on the phase of the day-night cycle and on the intensity of light. These data strongly suggest that the circadian pacemaker modulates human HR.

Bivariate genetic analysis of fasting insulin and glucose levels.

The main aim of this study was to estimate the relative influence of genes and environment on fasting insulin levels, which were considered a proxy of insulin resistance. Possible sex differences in genetic and environmental influences, and the origin of the covariance between fasting insulin and glucose were investigated. Subjects were 209 pairs of middle-aged twins, divided into 5 sex-by-zygosity groups. A general bivariate model and a reciprocal causation model including fasting insulin and glucose were used in the analyses. For both quantitative genetic models, a model specifying additive genetic and unique environmental factors, which were the same in males and females, showed the best fit to the data. Heritability estimates were modest and highly similar in both models: 20-25% of the variance in fasting insulin, and around 50% of the variance in fasting glucose levels could be attributed to genetic factors. The two models could not be discriminated on the basis of their fit to the data. A submodel of the general bivariate model suggested that the covariance between glucose and insulin has a unique environmental basis, whereas for the reciprocal causation model both causal paths were needed to explain the phenotypic correlation between insulin and glucose and estimates of the reciprocal paths were of opposite sign, an indication for the expected negative feedback loop.

Epinephrine-induced panic attacks and hyperventilation.

To assess the effects of epinephrine on ventilation in patients with panic disorder and in social phobics, analyses were performed on pooled data from two previous infusion studies. Throughout the infusion, changes in transcutaneous PCO2 (tcPCO2), subjective anxiety, heart rate and blood pressure were recorded continuously. Twenty-nine patients received epinephrine, ten patients received placebo. Thirteen patients (45%) had a panic attack during epinephrine. The fall in tcPCO2 and the cardiovascular response was greater in panicking patients than patients who did not panic. Although the fall in tcPCO2 associated with panic was not substantial and did not indicate clinically significant acute hyperventilation, it appears to be a sensitive index for epinephrine-induced panic. The fall in tcPCO2 was predicted rather by the frequency of occurrence of anxiety-related somatic symptoms than by the fear of these symptoms. These findings further reduce a role for fear of bodily sensations in epinephrine-induced panic attacks and favor a biological sensitivity to sympathetic stimulation.

Serum lipids and cardiovascular reactivity to stress.

Several studies have reported an association between serum lipid levels and cardiovascular reactivity to laboratory stressors. Their findings, however, are equivocal. The inconsistencies may be due to shortcomings such as the small number of subjects, the inclusion of patient groups, no control for medication, and no control for age effects. Two studies are presented investigating the relationship in large groups of adolescent and middle-aged males and females. Cholesterol, triglycerides and HDL were measured. Subjects were exposed to mental stressors, and in one study also to a cold pressor test. In addition to heart rate and blood pressure, in one study impedance cardiography was used to measure pre-ejection period, stroke volume and total peripheral resistance. Canonical correlation analysis suggested an association between triglycerides and decreased cardiac reactivity to mental stressors in middle-aged females. Trends in the same direction were found in both middle-aged males and females with respect to reactivity to the cold pressor. These associations, however, were not confirmed when the extreme deciles of the triglyceride distributions were compared with respect to stress reactivity. The fact that associations were completely absent in youngsters but sometimes showed up in older persons suggested an age dependency of the association. In post hoc analyses, indeed, some evidence was found for stronger cardiac responsivity being associated with cholesterol specifically in relatively older males. In females, in contrast to this, the association between triglycerides and cardiac responsivity was stronger in the younger group. More detailed measurement techniques, of specifically vascular processes, may be needed to explore further the effects of sex and age on the association between lipids and stress reactivity.