Are psychophysiological arousal and self-reported emotional stress during an oncological consultation related to memory of medical information? An experimental study.

Patients forget 20-80% of information provided during medical consultations. The emotional stress often experienced by patients during consultations could be one of the mechanisms that lead to limited recall. The current experimental study therefore investigated the associations between (analog) patients' psychophysiological arousal, self-reported emotional stress and their (long term) memory of information provided by the physician. One hundred and eighty one cancer-naïve individuals acted as so-called analog patients (APs), i.e. they were instructed to watch a scripted video-recoding of an oncological bad news consultation while imagining themselves being in the patient's situation. Electrodermal and cardiovascular activity (e.g. skin conductance level and heart rate) were recorded during watching. Self-reported emotional stress was assessed before and after watching, using the STAI-State and seven Visual Analog Scales. Memory, both free recall and recognition, was assessed after 24-28 h. Watching the consultation evoked significant psychophysiological and self-reported stress responses. However, investigating the associations between 24 psychophysiological arousal measures, eight self-reported stress measures and free recall and recognition of information resulted in one significant, small (partial) correlation (r = 0.19). Considering multiple testing, this significant result was probably due to chance. Alternative analytical methods yielded identical results, strengthening our conclusion that no evidence was found for relationships between variables of interest. These null-findings are highly relevant, as they may be considered to refute the long-standing, but yet untested assumption that a relationship between stress and memory exists within this context. Moreover, these findings suggest that lowering patients' stress levels during the consultation would probably not be sufficient to raise memory of information to an optimal level. Alternative explanations for these findings are discussed.

Infection load as a predisposing factor for somatoform disorders: evidence from a Dutch General Practice Registry.

OBJECTIVE: Somatoform disorders (SDs) are characterized by chronic multiple functional somatic (FS) symptoms. It has been suggested that infections may be triggers for FS symptoms to occur, pointing to the immune system as a pathogenic factor in their development. The current study aimed to compare the prevalence of infections (i.e., infection load) in the history of patients with SDs with that of matched controls. METHODS: Samples (n = 185) were identified in the Psychiatric Case Register Middle Netherlands and the Julius General Practitioners Network. Patients with an SD diagnosis in the Psychiatric Case Register Middle Netherlands were compared with matched persons without somatoform complaints (controls) on their infection load in two periods before the date of the psychiatric diagnosis or a matched date for the controls (i.e., the total period for which data were available and a 3-year period). Infection load was defined as the total number of infections documented in the Julius General Practitioners Network. RESULTS: Patients with SD had significantly more infections than did controls in both periods (total period: mean [standard error] = 0.87 [0.10] versus 0.51 [0.06], z = -3.08, p = .002; 3-year period: 3.44 [0.47] versus 2.15 [0.50], z = -2.91, p = .004). CONCLUSIONS: Results show that patients with SD have a higher infection load preceding their diagnosis as compared with matched controls, implicating that infection load may indeed predispose for developing FS symptoms. These findings emphasize the importance of further research on immunological mechanisms in FS symptoms. Limitations of the study are discussed.

Fatigue, depressive symptoms, and anxiety from adolescence up to young adulthood: a longitudinal study.

Fatigue is a common complaint among adolescents. We investigated the course of fatigue in females during the transition from adolescence to young adulthood and examined psychological, immunological, and life style risk factors for development of fatigue and chronic fatigue syndrome (CFS)-related symptoms. Six hundred and thirty-three healthy females (age 14.63±1.37 years) filled out questionnaires measuring fatigue severity, depressive symptoms, anxiety, chronic fatigue syndrome (CFS)-related symptoms, sleep features, and life style characteristics at baseline and 4½ years thereafter. Of 64 participants LPS- and CD2CD28-induced cytokine data at baseline were available. The best predictor of fatigue in young adulthood was previous fatigue severity. In participants who were non-fatigued during adolescence and who experienced a notable increase in fatigue, fatigue development was preceded by emotional problems and CFS-related complaints during adolescence. Increases as well as decreases in fatigue severity were accompanied by respectively increase and decrease in depressive symptoms and anxiety, suggesting that these symptoms cluster and co-vary over time. Higher interferon (IFN)-γ, higher IFN-γ/interleukin (IL)-4 ratio, lower tumor necrosis factor-α and lower IL-10 at baseline were related to fatigue severity at follow up. The rise in total number of CFS-related symptoms at follow up was predicted by anxiety and decreased physical activity during adolescence. Sleep and substance use were associated with fatigue severity and anxiety and depression. In conclusion, vulnerability to develop fatigue and associated symptoms in young adulthood can to a certain extent be identified already years before the manifestation of complaints.

Health and physiological effects of an emotional disclosure intervention adapted for application at home: a randomized clinical trial in rheumatoid arthritis.

BACKGROUND: The efficacy of emotional disclosure in alleviating psychological and physical stress has been well documented in controlled laboratory studies. A next step is to evaluate its clinical utility in 'real world' settings. We adapted the emotional disclosure intervention for use in home-based settings by stimulating the suggested effective ingredients of cognitive-emotional processing, and evaluated its psychological and clinical effectiveness. Reviews indicated the need to examine the physiological changes brought about by emotional disclosure, which may be particularly relevant in immune-mediated diseases. This study was the first to examine neuroendocrine and immune changes after emotional disclosure in patients with rheumatoid arthritis. METHODS: Sixty-eight patients were randomly assigned to four weekly oral emotional disclosure or time management sessions. At baseline and 1 week and 3 months after the sessions, depressed and cheerful mood, joint scores, erythrocyte sedimentation rate, cortisol, noradrenaline, interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and IL-10 were evaluated. Repeated measures analyses of variance were performed. RESULTS: No effect on psychological well-being and clinical outcome was found (p > or = 0.10). Cortisol (p = 0.01) and the serum level of the pro-inflammatory cytokine IFN-gamma (p = 0.05) were differentially affected by the two conditions. The change of IL-6 nearly reached significance (p = 0.07). CONCLUSIONS: The physiological changes are in agreement with theories on the mechanisms underlying emotional disclosure benefits and are suggestive of better disease control after emotional disclosure. General and study-specific reasons for the absence of psychological and clinical effects are discussed. The findings warn against widespread implementation of this home-based emotional disclosure intervention in unselected rheumatoid arthritis samples.

Salivary cortisol and binge eating disorder in obese women after surgery for morbid obesity.

BACKGROUND: Binge eating episodes characterized by loss of control are hypothesized to be accompanied by changes in hypothalamic pituitary adrenal (HPA) axis functioning. Cortisol is an end product of this neuroendocrine stress system. PURPOSE: The aim of this study was to examine the cortisol levels and the awakening cortisol response (ACR) in obese persons showing binge eating after surgery for morbid obesity. METHOD: Sixteen obese women with binge eating disorder (BED) and 18 obese women without BED participated in the study. Means+/-SD: age 43 +/- 15, body mass index 40 +/- 8. Salivary cortisol, anthropometric assessments, and the eating disorder examination interview were taken. RESULTS: Women with BED showed a significantly lower waist-to-hip ratio and cortisol levels during the day than women without BED, whereas the ACR did not differ. CONCLUSION: Our cross-sectional study in a small sample generates the hypothesis that neuroendocrine regulation differs between obese women with and without BED after obesity surgery. This finding needs replication in future studies that should also examine the causal direction of the observed association.

Does silence speak louder than words? The impact of oncologists' emotion-oriented communication on analogue patients' information recall and emotional stress.

OBJECTIVE: The impact of two types of oncologists' emotion-oriented communication on participants' recall of medical information was investigated, and the potential mediation by a reduction in emotional stress. Additionally, moderation effects by personal characteristics were explored. METHODS: An oncologist's communication in response to a patient's emotional expressions was manipulated during a videotaped, scripted bad-news consultation. Three conditions were created: 1) standard communication, 2) emotion-oriented silence, and 3) emotion-oriented speech. Participants (N = 217) were randomly allocated to one of the three conditions. Measurements included information recall (free recall and recognition), emotional stress (self-reported and physiological), and personal characteristics. RESULTS: Emotion-oriented silence (p = .002) and speech (p = .019) enhanced information recognition compared to standard communication. No differences in free recall were found. Emotional stress did not mediate these relations. Poorer functional health literacy predicted poorer recognition, but this was counteracted by emotion-oriented communication. CONCLUSIONS: By means of acknowledging, exploring, empathic and supportive statements, and attentive silence, the oncologist's communication resulted in better information recognition. How oncologists' communication impacts patients' information recall warrants further investigation, as this could not be explained by reducing emotional stress. PRACTICE IMPLICATIONS: These insights will help educators to validate the relevance of emotion-oriented strategies, and encourage oncologists to adopt them.

Glucocorticoid sensitivity of immune cells in severely fatigued adolescent girls: a longitudinal study.

Fatigue during adolescence is associated with somatic and psychological complaints that resemble the pattern of symptoms described for chronic fatigue syndrome (CFS). Studies in CFS and other stress-related syndromes suggested a dysfunction of the interactions between the hypothalamic-pituitary-adrenal axis (HPA-axis) and the immune system, i.e. a changed glucocorticoid (GC) receptor sensitivity of immune cells, to exist. Here we investigated whether severely fatigued girls from a healthy population have altered cortisol production and immune cell sensitivity for the synthetic GC, dexamethasone (DEX). In a longitudinal design, we examined ex vivo DEX sensitivity of monocytes and of T-cell mitogen-induced responses of severely fatigued (N=65) and non-fatigued girls (N=60). Fatigued girls reported more severe comorbid complaints than non-fatigued participants across three measurements during 1 year (T1: spring, T2: autumn, T3: spring) and had higher plasma cortisol levels throughout the study. DEX sensitivity of T-cell mitogen-induced responses showed seasonal variation with increased sensitivity in autumn compared to spring. No systematic variation of monocyte glucocorticoid receptor (GR) sensitivity was observed. Significant rank correlations of DEX sensitivity of T-cell mitogen-induced responses between the three assessments during the year suggest a stable trait of immune function. Groups did not differ in DEX sensitivity on any of the read outs. However, in a persistently fatigued subgroup, sensitivity to DEX was significantly reduced on the level of interferon (IFN)-gamma production. These results show that although fatigued participants had severe (comorbid) complaints, only in the case when symptoms persisted, altered GC sensitivity of immune cells was observed.

The HPA-axis and immune function in burnout.

Burnout results from chronic work stress. Its complaints may be related to HPA-axis disturbances or changes in immune function. In our studies the salivary cortisol awakening response, day-curve, and the suppressed level after dexamethasone intake were not different in a burned-out group compared to a control group. Nor was there a change in cortisol after a treatment period. Higher levels of DHEAS and the monocyte released anti-inflammatory cytokine IL-10 were observed, however T-cell stimulated and dexamethasone inhibited cytokine release were not affected. The increased IL-10 level may be related to an increased sensitivity for infections.

Lay trainers with migraine for a home-based behavioral training: a 6-month follow-up study.

OBJECTIVE: To evaluate the changes at 6-month follow-up after a home-based behavioral training (BT) provided by lay trainers with migraine to small groups of fellow patients. BACKGROUND: The need for self-management programs and cost-effective treatments gave rise to this study. METHODS: In a previous randomized controlled trial, we compared the BT group with a waitlist-control group, receiving usual care. The control group was trained directly after their waitlist period. The present study examined the follow-up results in both groups and measurements were held pre BT, post BT, and at 6-month follow-up. RESULTS: Six months after BT, 42% was categorized as responders (>or=-50% decrease in attack frequency), 42% did not change (-49 to 49%), and 16% responded adversely (>or=50% increase). In the group as a whole (n = 95), attack frequency significantly decreased from 3.0 attacks at baseline to 2.5 post BT and to 2.3 at 6-month follow-up (-23%, medium effect size 0.6). The strong improvements of perceived control over and self-confidence in attack prevention were maintained at follow-up. Disability and health status were unchanged but quality of life significantly improved over time (P = .007). BT was more beneficial for patients who entered the training with a high attack frequency. Linear regression analysis demonstrated that a stronger belief at baseline that the occurrence of migraine is due to chance (external control) significantly predicted a lower attack frequency at follow-up. CONCLUSION: Lay trainers with migraine can train small groups of fellow patients at home in behavioral attack prevention. At 6-month follow-up, attack frequency and quality of life were significantly but modestly improved and feelings of control and self-confidence remained strongly improved.

Emotions and emotional approach and avoidance strategies in fibromyalgia.

OBJECTIVE: Disturbances in emotional functioning may contribute to psychological and physical symptoms in patients with fibromyalgia. This study examined emotions and emotion-regulation strategies in women with fibromyalgia and in controls, and how these variables relate to symptoms of fibromyalgia. METHODS: We compared 403 women with fibromyalgia to 196 control women using self-report questionnaires. RESULTS: Negative emotions and the use of emotional-avoidance strategies were elevated, and positive emotions were reduced, in fibromyalgia patients; the alexithymia scale "difficulty identifying feelings" showed a large deviation from normal. Emotional-approach measures were not deviant. In the fibromyalgia sample, emotional-avoidance strategies were highly correlated with more mental distress and were modestly correlated with more pain and fatigue, while emotional-approach strategies were only minimally related to better functioning. We tested two interaction models. The intense experiencing of emotions was related to more pain only in patients who lack the ability to process or describe emotions. Although fibromyalgia patients showed deficits in the experiencing of positive affect, positive affect did not buffer the association between pain and negative affect. CONCLUSION: This study demonstrates increased negative emotions and decreased positive emotions, as well as increased emotional-avoidance strategies, in women with fibromyalgia. Research should test whether interventions that reduce emotional avoidance lead to health improvements in women with fibromyalgia.

Influence of sleep on symptom improvement and return to work in clinical burnout.

OBJECTIVES: The current study examined the extent to which symptom improvement and full return to work occurs among clinically burnt-out employees and what the influence of concurring sleep problems is with respect to health recovery. METHODS: Fifty-nine burnt-out employees on extended sick leave assessed their symptoms for 2 weeks using an electronic diary. After 6 months, the measurements were repeated. Symptom levels were compared with those of a healthy reference group that was assessed only once. RESULTS: After 6 months, all burnout symptoms had decreased significantly, and full return to work was achieved by 37% of the burnt-out individuals. The symptom levels at 6 months of follow-up among those who had fully returned to work were similar to healthy levels and significantly lower than the levels of those still on sick leave. The persons who benefited poorly from sleep at baseline had higher exhaustion levels at follow-up than those who benefited from sleep. Trouble falling asleep and less refreshing sleep at baseline hampered eventual full work resumption. CONCLUSIONS: The results show that a significant number of clinically burnt-out employees is able to recover in a 6-month period and that sleep plays an important role both in symptom improvement and in return to work.

Cortisol and severe fatigue: a longitudinal study in adolescent girls.

Fatigue is a common complaint among adolescents, especially in girls, and is associated with high rates of school absenteeism. Severe fatigue is often accompanied by psychological and physical symptoms. In the chronic fatigue syndrome (CFS) functioning of the hypothalamic-pituitary-adrenal (HPA)-axis has previously been found to be altered. The aim of the present study was to investigate whether cortisol production is deviant in fatigued adolescent girls from the general population and to study longitudinal changes in fatigue in association with possible changes in HPA-axis functioning. In the cross-sectional part of the study the cortisol response to awakening (CAR) and to a low-dose oral dexamethasone were examined in a group of fatigued adolescent girls (n=87) in comparison to a non-fatigued control group (n=77). Questionnaires regarding fatigue, depression, anxiety, sleep quality, somatic symptoms and CFS-related symptoms were filled out. Follow up measurements were performed after 6 and 12 months. While the fatigued and non-fatigued group differed remarkably on all symptom self-reports, no differences between groups in CAR and response to dexamethasone were observed. Girls in the fatigued group remained fatigued over time and reported high levels of other psychological and physical symptoms during the whole year of the study. The CAR varied between time points but correlated non-systematically with situational characteristics or symptom reports. We conclude that trait-like fatigue, as measured in a sample of adolescent girls from a high school population, is not reflected in a dysregulation as assessed on the level of salivary cortisol after awakening.

Medically unexplained symptoms and between-group differences in 24-h ambulatory recording of stress physiology.

People with medically unexplained symptoms (MUS) often have a comorbid history of stress and negative affect. Although the verbal-cognitive and (peripheral) physiological stress systems have shown a great degree of independence, at the same time it is claimed that chronic stress and negative affect can result in a disregulated physiological stress system, which may lead to MUS. Previous studies could not demonstrate a straightforward between subject relationship between MUS and stress physiology, supporting the view of independence. The aim of the current study was to further explore this relationship using an improved methodology based on ecologically valid 24-h real-life ambulatory recordings. Seventy-four participants (19 male; 55 female) with heterogeneous MUS were compared with 71 healthy controls (26 male; 45 females). Momentary experienced somatic complaints and mood, heart rate, cardiac autonomic activity, respiration and saliva cortisol were monitored using electronic diary and ambulatory registration devices. Participants with MUS reported much more momentary complaints and negative affect as compared to controls. Although MUS seemed to be associated with elevated heart rate and reduced low and very-low frequency heart period variability, these effects disappeared after controlling for differences in sports behaviour. No group differences were found for cardiac autonomic activity, respiration, end-tidal CO(2) and saliva cortisol. Our 24-h real-life ambulatory study did not support the existence of a connection between MUS and disregulated peripheral stress physiology. Future studies may instead focus on central measures to reveal potential abnormalities such as deviant central processing of visceral signals in MUS patients.

Exhaustion and endocrine functioning in clinical burnout: an in-depth study using the experience sampling method.

The current study investigates the relationship between HPA-axis functioning and burnout symptoms by employing an electronic symptom diary. This diary method circumvents the retrospection bias induced by symptom questionnaires and allows to study relationships within-in addition to between-subjects. Forty two clinically burned-out participants completed the exhaustion subscale of the Maslach burnout inventory and kept an electronic diary for 2 weeks to assess momentary exhaustion and daily recovery through sleep. On 3 consecutive weekdays within the diary period, saliva was sampled to determine the cortisol awakening response (CAR), levels of dehydroepiandrosterone-sulphate (DHEAS) on the first 2 weekdays, and to conduct the dexamethasone suppression test (DST) on the third weekday. We found significant relationships between endocrine values and general momentary symptom severity as assessed with the diary, but not with the retrospective questionnaire-assessed burnout symptoms. Simultaneous assessments of endocrine values and burnout symptoms assessed with the diary after awakening rendered significant associations between persons, and a trend within persons. More severe burnout symptoms were consistently associated with a lower level and smaller increase of CAR, higher DHEAS levels, smaller cortisol/DHEAS ratios and a stronger suppression after DST. Burnout symptoms were significantly related to endocrine functioning in clinical burnout under the best possible conditions of symptom measurement. This adds support to the view that severity of burnout symptoms is associated with HPA-axis functioning.

Evidence that impaired sleep recovery may complicate burnout improvement independently of depressive mood.

OBJECTIVE: This article examines recovery through sleep in relation to sleep quality, exhaustion, and depression in clinical burnout. We focus on actual recovery per night, given its relevance to burnout improvement. METHODS: Sixty clinically burned-out participants and 40 healthy controls recorded symptoms with an electronic diary for 2 weeks at random times per day. Recovery through sleep was defined as the difference in fatigue between late evening and the next morning. RESULTS: In clinical burnout, sleep quality and recovery are impaired, and depression is elevated. Poor recovery through sleep is associated with poor same-night sleep quality, clarifying the mechanisms underlying poor recovery. Individual differences in recovery though sleep were related to differences in refreshed awakening, but not to other sleep problems. Impaired recovery was also related to severity of exhaustion, but not to severity of depressive mood, indicating that, in burnout, nonprofit from sleep is a symptom of energy depletion, not a sign of depression. CONCLUSION: Impaired recovery through sleep may hamper recovery from burnout independently of the influence of depression.

Sex differences and heritability of two indices of heart rate dynamics: a twin study.

We investigated whether women show larger heart rate variability (HRV) than men after controlling for a large number of health-related covariates, using two indices of HRV, namely respiratory sinus arrhythmia (RSA) and approximate entropy (ApEn). In a twin design, the heritability of both indices was examined. The covariation between RSA and ApEn, a measure of heart rate dynamics derived from nonlinear dynamical systems theory, was decomposed into genetic and environmental components. Subjects were 196 male and 210 female middle-aged twins. Females showed larger HRV than men before (ApEn: p < .001; RSA: p = .052) and after adjustment for covariates (ApEn: p < .001; RSA: p = .015). This sex difference was confirmed by significant intrapair differences in the opposite-sex twin pairs for both ApEn (p < .001) and RSA (p = .03). In addition to sex, only heart period and age (both p < .001) were found to be independent predictors of ApEn, whereas RSA was also influenced by respiration rate and smoking (both p < .001). Age explained 16% and 6% of the variance in RSA and ApEn, respectively. Oral contraceptive use and menopausal status had no effect on HRV. Genetic model fitting yielded moderate heritability estimates for RSA (30%) and ApEn (40%) for both males and females. The correlation between RSA and ApEn (r = .60) could be attributed to genetic factors (48%), environmental factors (36%) and age (16%). The present study found support for a gender difference in HRV with women having greater HRV than men even after controlling for a large number of potential confounders. Indices of heart rate dynamics derived from nonlinear dynamical systems theory are moderately heritable and may be more sensitive than traditional indices of HRV to reveal subtle sex differences with important implications for health and disease.

Feasibility and induced cognitive-emotional change of an emotional disclosure intervention adapted for home application.

OBJECTIVE: Emotional engagement, cognitive restructuring, and positive future directedness are considered core elements to induce change in emotional disclosure interventions. Our aim was to examine the induction of these elements and the feasibility of an emotional disclosure intervention adapted for home application. METHODS: The intervention emphasized expression of negative and positive emotions (session 1-4), search for meaning (session 3), and a positive future-oriented ending (session 4). A randomized clinical trial in patients with rheumatoid arthritis compared the adapted intervention (n=40) with a time management control condition (n=28). Feasibility was evaluated regarding adherence, compliance with instructions, perceived viability, and clinical safety. Induction of core elements was evaluated by analysis of change in immediate affective responses and by computerized text analysis of word use. RESULTS: Feasibility criteria were successfully met. The disclosure condition produced higher immediate negative affect and use of emotion, insight, and optimism words compared to control, and induced the elements of change within sessions as intended. CONCLUSION: The adapted intervention is feasible for home application and induces change in variables that indicate emotional engagement, cognitive restructuring, and positive future directedness. PRACTICE IMPLICATIONS: Empirical support of health benefits of this emotional disclosure intervention will extend its applicability in patient self-care.

Mobile Web-based monitoring and coaching: feasibility in chronic migraine.

BACKGROUND: The Internet can facilitate diary monitoring (experience sampling, ecological momentary assessment) and behavioral coaching. Online digital assistance (ODA) is a generic tool for mobile Web-based use, intended as an adjuvant to face-to-face or Internet-based cognitive behavioral treatment based. A current ODA application was designed to support home-based training of behavioral attack prevention in chronic migraine, focusing on the identification of attack precursors and the support of preventive health behaviour. OBJECTIVE: The aim was to establish feasibility of the ODA approach in terms of technical problems and participant compliance, and ODA acceptability on the basis of ratings of user-friendliness, potential burden, and perceived support of the training for behavioral attack prevention in migraine. METHODS: ODA combines mobile electronic diary monitoring with direct human online coaching of health behavior according to the information from the diary. The diary contains three parts covering the following: (1) migraine headache and medication use, (2) attack precursors, and (3) self-relaxation and other preventive behavior; in addition, menstruation (assessed in the evening diary) and disturbed sleep (assessed in the morning diary) is monitored. The pilot study consisted of two runs conducted with a total of five women with chronic migraine without aura. ODA was tested for 8.5 days (range 4-12 days) per participant. The first test run with three participants tested 4-5 diary prompts per day. The second run with another three participants (including one subject who participated in both runs) tested a reduced prompting scheme (2-3 prompts per day) and minor adaptations to the diary. Online coaching was executed twice daily on workdays. RESULTS: ODA feasibility was established on the basis of acceptable data loss (1.2% due to the personal digital assistant; 5.6% due to failing Internet transmission) and good participant compliance (86.8% in the second run). Run 1 revealed some annoyance with the number of prompts per day. Overall ODA acceptability was evident by the positive participant responses concerning user-friendliness, absence of burden, and perceived support of migraine attack prevention. The software was adapted to further increase the flexibility of the application. CONCLUSIONS: ODA is feasible and well accepted. Tolerability is a sensitive issue, and the balance between benefit and burden must be considered with care. ODA offers a generic tool to combine mobile coaching with diary monitoring,independently of time and space. ODA effects on improvement of migraine remain to be established.

Electronic diary evidence on energy erosion in clinical burnout.

Burnout is generally defined as a state of severe exhaustion. So far, research has predominantly focused on relatively mild burnout in employees able to work despite their complaints. This study examines energy depletion in clinical burnout (e.g., the severest cases on extended sick leave) by comparing the diurnal patterns of fatigue and exhaustion with those of healthy individuals. Sixty clinically burned-out and 40 healthy participants kept an electronic diary for 14 days, 7 times a day, yielding a total of 8,116 diary entries. This study shows that burned-out individuals typically suffer continuously from a severe fatigue throughout the day. The resulting flattened diurnal cycles mark a stable exhaustion that is uncommon in healthy persons. The current results provide novel support for the existence of severe energy erosion in clinical burnout.

Genetic influences on fibrinogen, tissue plasminogen activator-antigen and von Willebrand factor in males and females.

Differences in genetic influence on death from CHD between males and females have been reported. Haemostatic factors have consistently been associated with risk for coronary heart disease (CHD), but sex differences in genetic architecture have not been studied. This study in middle-aged twins investigates whether there are sex differences in means and in genetic and/or environmental variance components of haemostatic risk factors for CHD. A total of 93 monozygotic twin pairs (44 male and 49 female) and 116 dizygotic twin pairs (36 male, 40 female and 40 opposite sex) were available for this study. Structural equation modelling was used to estimate the relative influence of genetic and environmental factors on variation in levels of fibrinogen, tissue plasminogen activator (tPA) antigen and von Willebrand factor (vWF). Mean levels of tPA and vWF increased with age. Oral contraceptive pill (OCP) and menopause had significant influences on levels of fibrinogen and tPA. Genetic influences explained 39, 66 and 72% of the variation in levels of fibrinogen, tPA and vWF, respectively. No quantitative or qualitative differences of genetic influences on haemostatic levels were seen between males and females. Haemostatic factors may account for a significant part of the genetic risk for cardiovascular disease. No difference in genetic architecture for levels of fibrinogen, tPA or vWF was observed between males and females.