Can the DEX/CRH test or markers of oxidative stress distinguish work-related stress from major depressive disorder and normal controls?

Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity measured by the combined dexamethasone-CRH test (DEX-CRH test) has been found in patients with major depressive disorder (MDD), whereas hypoactivity has been found in patients with work-related stress. We aimed to investigate the DEX-CRH test as a biomarker to distinguish between MDD and work-related stress (exhaustion disorder - ED). We hypothesized that there would be lower cortisol and ACTH response in participants with ED compared to MDD and healthy controls (HC). Also, we explored if the cortisol response of those patients interacted with robust markers of oxidative stress. Thirty inpatients with MDD and 23 outpatients with ED were recruited. Plasma cortisol and ACTH were sampled during a DEX-CRH test. The main outcome measure, area under the curve (AUC) for cortisol and ACTH, was compa-red between MDD vs. ED participants and a historical HC group. Secondary markers of oxidative stress urinary 8-oxodG and 8-oxoGuo; quality of sleep and psychometrics were obtained. Cortisol concentrations were higher in MDD and ED participants compared to HC, and no differences in AUC cortisol and ACTH were found between ED vs. MDD. Compared to ED, MDD participants had higher stress symptom severity and a lower sense of well-being. No differences in oxidative stress markers or quality of sleep between the groups were found. The result indicates that the patients with ED, like patients with MDD, are non-suppressors in DEX-CRH test and not hypocortisolemic as suggested.

Do objective and subjective measures of cognitive impairment predict occupational status in patients with work-related stress? A clinical follow-up study.

OBJECTIVE: Cognitive impairment is a common complaint in prolonged work-related stress and may contribute to work disability. The objective was to evaluate the longitudinal impacts of objectively and subjectively measured cognitive impairment on occupational status and to evaluate the measurement's predictive properties regarding occupational prognosis in patients with work-related stress. METHODS: Patients with work-related stress (n = 82) were assessed with Danish versions of the Screen for Cognitive Impairment in Psychiatry (SCIP-D) and the Cognitive Failure Questionnaire (CFQ), as screeners of objective and subjective cognitive impairments, respectively. Patients were contacted via telephone at 6-month follow-up providing data on occupational status (employment vs. non-employment). Impacts of cognitive impairment on occupational status were evaluated using logistic regression analyses adjusting for other explanatory covariates (sociodemographic factors, comorbidities etc.). The predictive performance of SCIP-D and CFQ were evaluated using non-adjusted logistic regression analysis and receiver-operating-characteristics curves. RESULTS: There was a strong association between objective cognitive impairment measured with SCIP-D and non-employment when adjusting for other explanatory factors (OR adjusted 3.25, 95% CI 1.09-9.69). The association was attenuated but remained robust in the non-adjusted analysis (OR non-adjusted 1.74, 95% CI 1.08-2.81). Yet, a cut-score of SCIP-D performed inadequate as a sole predictor of occupational status. Subjective cognitive impairment was unrelated to subsequent occupational status. CONCLUSIONS: Objective-but not subjective-cognitive impairment was associated with subsequent non-employment. Our results suggest a predictive potential in objective measurements of cognitive impairment with significant implications for clinical assessment of patients with work-related stress.

Developing a prognostic model for stress reduction in patients with prolonged work-related stress.

Mindfulness-based stress reduction (MBSR) is a 9-session group-treatment programme for managing stress. Research suggests variability in the outcomes of MBSR among participants. This prognostic (not causal) study develops a multivariable model that may support clinicians in forecasting expected MBSR outcomes. We used data of 763 patients collected from MBSR programs conducted between October 2015 and March 2022. Candidate prognostic factors at baseline included psychosocial work environment, sociodemographic, and clinical information. Multiple imputation was used to handle missing data (imputations = 200). Important prognostic factors were backward selected in ≥5% of the imputed datasets. The final prediction model including the selected prognostic factors was evaluated using linear regression with a four-fold internal cross-validation procedure. Reductions in perceived stress from baseline to end of the MBSR programme were predicted by a lower General Severity Index (ß = 2.00, p < 0.01), higher baseline levels of stress (ß = -0.88, p < 0.01), and somewhat by having managerial responsibility in the latest job (vs. no; ß = -2.53, p = 0.07). The remaining prognostic factors were weaker predictors, for example, gender and income. Internal validity of the final model was indicated by consistent results from four randomly folded subsamples. This study developed a prognostic model predicting changes in stress levels in relation to the MBSR programme. A reduction in stress level was particularly predicted by milder psychological symptoms and higher baseline levels of perceived stress. These predictions cannot be taken as evidence of causal associations. Forecasting of the illness course should be cautiously practiced using clinical judgement regarding individual patients.

Screening for cognitive impairment among patients with work-related stress complaints in Denmark: validation and evaluation of objective and self-report tools.

OBJECTIVE: Many patients with work-related stress display cognitive impairment that may hamper recovery. We examined objective and subjective tools for screening of cognitive impairment in this patient group. METHODS: Patients were assessed with Danish versions of the objective Screen for Cognitive Impairment in Psychiatry (SCIP-D), standardized neuropsychological tests that tapped into the same cognitive domains, the self-assessed Cognitive Failure Questionnaire (CFQ), and several additional scales of symptom severity and psychosocial status. Concurrent validity of the SCIP-D and CFQ was assessed by calculation of Pearson's correlation coefficients between the objective and subjective tools and the scores on more conventional standardized neuropsychological tests. Decision validity was assessed with logistic receiver-operating-characteristic analyses using a cut-score approach to the objective and the subjective test results to predict impairment detected by the standardized tests. Cognitive norms were established through the data of 79 healthy controls. SCIP-D scores were compared between patients and healthy controls with independent t-tests. RESULTS: We included 82 patients with work-related stress. The SCIP-D total scores were strongly associated with standardized neuropsychological tests (r=0.76, P<0.001). The self-assessed CFQ was not associated with either measure of objective cognitive functioning (r≤0.12, P≥0.30). The optimal SCIP-D total-score cut of ≤72 identified 43.2% of the patients with global objective cognitive impairment. The patients performed mildly-to.moderately lower than the healthy controls on the SCIP-D total score (Cohen's d=0.39) and the subtests for working memory (d=0.39) and processing speed (d=0.61). CONCLUSION: The SCIP-D is a valid screening tool sensitive to objective performance-based cognitive impairment among patients with work-related stress.

Work-related exposure to violence or threats and risk of mental disorders and symptoms: a systematic review and meta-analysis.

Objective This review aimed to examine systematically the epidemiological evidence linking work-related exposure to violence and threats thereof with risk of mental disorders and mental ill-health symptoms. Methods We searched PubMed, EMBASE, PsycINFO and Web of Science to identify original studies that provide quantitative risk estimates. The evidence was weighted according to completeness of reporting, potential common method bias, and bias due to differential selection and drop out, selective reporting, and misclassification of exposure and outcome. Results We identified 14 cross-sectional and 10 cohort studies with eligible risk estimates, of which 4 examined depressive disorder and reported an elevated risk among the exposed [pooled relative risk (RR) 1.42, 95% confidence interval (CI) 1.31-1.54, I 2=0%]. The occurrence of depressive and anxiety symptoms, burnout and psychological distress was examined in 17 studies (pooled RR 2.33, 95% CI 3.17, I 2=42%), and 3 studies examined risk of sleep disturbance (pooled RR 1.22, 95% CI 1.09-1.37, I2=0%). In most studies, common method bias and confounding could not be ruled out with confidence and strong heterogeneity in most outcome definitions invalidate the strict interpretation of most pooled risk estimates. Conclusion The reviewed studies consistently indicate associations between workplace violence and mental health problems. However, due to methodological limitations the causal associations (if any) may be stronger or weaker than the ones reported in this study. Prospective studies with independent and validated reporting of exposure and outcome and repeated follow-up with relevant intervals are highly warranted.

[Work-related stress and the hypothalamic-pituitary-adrenal axis].

This is a review on the topic of work-related stress (WRS), and how difficulities with differential diagnostics often arise because of overlapping symptoms between WRS and depression. Investigation into the hypothalamic-pituitary-adrenal (HPA) axis deviations seems to reveal the HPA axis as a promising biomarker, since studies have shown, that patients with melancholic type depression exhibit hyper-cortisolism, while patients with WRS exhibit hypocortisolism. More studies of better quality are needed, before anything conclusive can be said. Consensus regarding definition and a development of diagnostic criteria for WRS, e.g. the Swedish "exhaustion disorder", could enable a better differentiation and contribute to more accurate treatment and research.

Total power and high frequency components of heart rate variability and risk factors for atherosclerosis.

INTRODUCTION: Low heart rate variability, HRV, is associated with diabetic neuropathy and with ischemic heart disease, IHD. The time context points to diabetes preceding changes in HRV, while changes in HRV precede the development of atherosclerosis and IHD. The purpose of the study was to analyse the association between the physiological risk factors of IHD and HRV in a prospective design. METHODS: In 1998 and 2002, data was gathered in a study concerning the risk factors for atherosclerosis. From among the participants it was possible to include 50 women and 24 men in a sub-study concerning HRV. Heart rate variability was measured partly during a clinical examination with exposure to a simple stress test, and partly during the first 4 h of sleep. The clinical examination, which lasted 45 min, resulted in 9, 5-minute HRV measurements, while the sleep period was divided into 2 periods of 2 h each, for which average HRV measurements were calculated. The associations between HRV and risk factors for IHD were analysed using the GLM, repeated measures method. As the dependent variables in the GLM analyses 11 levels (9 while awake and 2 while sleeping) of total power and high frequency variability, respectively, were used. The included risk factors were; body mass index, waist-hip ratio, systolic blood pressure, fibrinogen, cholesterol, HDL-cholesterol, HbA1c, testosterone, DHEAs, cortisol and catecholamines. Catecholamines were measured in urine and only in 1998. Cortisol was measured in both urine and saliva in 1998, but only in saliva in 2002. The results were adjusted according to the starting time of the measurements. RESULTS: Among the women, waist-hip ratio and HbA1c were significantly and negatively associated with both TP and HF. Stress hormones were not associated with HRV. Among the men, waist-hip ratio, HbA1c, and fibrinogen in 2002, and cortisol and noradrenaline in 1998 were significantly and negatively associated with TP and HF. CONCLUSION: The study showed gender differences in the observed associations. In both gender, waist ratio and HbA1c were negatively associated with TP and HF. Furthermore, in the men, but not in the women, stress hormones in 1998, i.e. cortisol and noradrenaline, was negatively associated with TP and HF. The presented data give rise to discussion of the pathophysiology behind heart rate variability and ischemic heart disease, which may be different between women and men.

Estimation of individual reference intervals in small sample sizes.

In occupational health studies, the study groups most often comprise healthy subjects performing their work. Sampling is often planned in the most practical way, e.g., sampling of blood in the morning at the work site just after the work starts. Optimal use of reference intervals requires that the population, on which the reference interval is based, is representative for the study group in question. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommends estimating reference interval on at least 120 subjects. It may be costly and difficult to gain group sizes of that order of magnitude for all topics in question. Therefore, new methods to estimate reference intervals for small sample sizes are needed. We present an alternative method based on variance component models. The models are based on data from 37 men and 84 women taking into account biological variation from various variables such as gender, age, BMI, alcohol, smoking, and menopause. The reference intervals were compared to reference intervals calculated using IFCC recommendations. Where comparable, the IFCC calculated reference intervals had a wider range compared to the variance component models presented in this study. The presented method enables occupational health researchers to calculate reference intervals for specific groups, i.e. smokers versus non-smokers, etc. In conclusion, the variance component models provide an appropriate tool to estimate reference intervals based on small sample sizes.

Psychosocial factors at home and at work and levels of salivary cortisol.

BACKGROUND: Salivary cortisol as a physiological measure of stress has attracted great interest in recent years. METHOD: A 55 women and 28 men, all healthy volunteers, were included in a study on psychosocial factors at work and at home and salivary cortisol. General linear models, univariate and repeated measures, respectively, were used to evaluate the associations between psychosocial factors and cortisol excretion measured six times during a working day. Age, physical activity, tobacco use and the time of the first saliva sample were used as covariates. RESULTS: In the women, high degrees of time pressure, effort and effort reward imbalance were significantly associated with higher levels of cortisol. In the men, high degrees of effort, effort reward imbalance and overcommitment were significantly associated with higher levels of cortisol. CONCLUSION: Psychosocial factors are of significance to the level of salivary cortisol. The study emphasises the benefits of taking physiological measurements of stress in epidemiological studies.

Corrigendum to "Prognostic Factors of Returning to Work after Sick Leave due to Work-Related Common Mental Disorders: A One- and Three-Year Follow-Up Study".

[This corrects the article DOI: 10.1155/2015/596572.].

Progression in intima media thickness--the significance of hormonal biomarkers of chronic stress.

OBJECTIVE: The pathophysiological pathways from stress caused by psychosocial stress to IHD has not been dealt with very extensively. The objective of this study was to analyse the association between cortisol levels and progression in intima media thickness (IMT). METHODS AND RESULTS: In 1998 and 2002, 95 participants went through a clinical investigation including ultrasound of the artery carotis communis. Progression in IMT was analysed in relation to levels of salivary cortisol in 1998 and the average levels of salivary cortisol in 1998/2002. Further, the significance of conventional coronary risk factors, testosterone and dehydro-epiandrosterone sulphate (DHEAS) were evaluated. Among the men, only age and HDL-cholesterol (negative) were significantly correlated with progression in IMT. Among the women, awakening cortisol response was significantly correlated with progression in IMT. Testosterone and DHEAS were borderline significantly associated (negatively) with progression in IMT in both genders. CONCLUSION: Progression in atherosclerosis were determined by different risk factors in women and men. The awakening cortisol response was of great importance to IMT progression in women but not in men.

Prognostic Factors of Returning to Work after Sick Leave due to Work-Related Common Mental Disorders: A One- and Three-Year Follow-Up Study.

The aim of this paper was to assess the prognostic factors of return to work (RTW) after one and three years among people on sick leave due to occupational stress. Methods. The study population comprised 223 completers on sick leave, who participated in a stress treatment program. Self-reported psychosocial work environment, life events during the past year, severity of the condition, occupational position, employment sector, marital status, and medication were assessed at baseline. RTW was assessed with data from a national compensation database (DREAM). Results. Self-reported high demands, low decision authority, low reward, low support from leaders and colleagues, bullying, high global symptom index, length of sick leave at baseline, and stressful negative life events during the year before baseline were associated with no RTW after one year. Low work ability and full-time sick leave at inclusion were predictors after three years too. Being single was associated with no RTW after three years. The type of treatment, occupational position, gender, age, and degree of depression were not associated with RTW after one or three years. Conclusion. The impact of the psychosocial work environment as predictor for RTW disappeared over time and only the severity of the condition was a predictor for RTW in the long run.

[Violence against health personnel]. / Vold mod læger og sundhedspersonale.

Health personnel are at risk of threats and violence, especially when young and inexperienced. Also, working in emergency departments, psychiatric wards, and eldercare bears a risk. The phenomenon is reported from all over the world and may originate in intoxication, confusion or frustration during long waiting hours and uncertainty of treatment and prognosis. Experiences of threats and violence result in decreased well-being, anger, helplessness and thoughts about change of workplace or quitting the job. Training in communication and teamwork may prevent threats and violence.

[Negative press coverage can lead to acknowledgement of occupational psychiatric disorder].

Some of the cases of acknowledged occupational psychiatric disorder in Denmark have been exposed to negative press coverage. Such individuals might have been exposed to violence to a lower extent than other with an acknowledged psychological work injury. We compared 25 cases with 35 controls matched on age and gender. The cases had experienced significantly fewer incidents of violence and had less anxiety and flashback symptoms than the controls. The results suggest that the negative press coverage was the reason for the psychiatric symptoms rather than exposures at the workplace.

Occurrence of delayed-onset post-traumatic stress disorder: a systematic review and meta-analysis of prospective studies.

OBJECTIVE: Post-traumatic stress disorder (PTSD) develops according to consensus criteria within the first 1-6 months after a horrifying traumatic event, but it is alleged that PTSD may develop later. The objective was to review the evidence addressing occurrence of PTSD with onset >6 months after a traumatic event (delayed-onset PTSD). METHODS: Through a systematic search in PubMed, EMBASE, and PsycINFO, we identified 39 studies with prospective ascertainment of PTSD. A meta-analysis was performed in order to obtain a weighted estimate of the average proportion of delayed-onset PTSD cases, and meta-regression was used to examine effects of several characteristics RESULTS: Delayed-onset PTSD was reported in all studies except one, and the average prevalence across all follow-up time was 5.6% [95% confidence interval (95% CI) 4.3-7.3%]. The proportion with delayed-onset PTSD relative to all cases of PTSD was on average 24.5% (95% CI 19.5-30.3%) with large variation across studies. In six studies with sub-threshold symptom data, delayed-onset PTSD seemed most likely an aggravation of early symptoms. The proportion with delayed-onset PTSD was almost twice as high among veterans and other professional groups compared to non-professional victims. CONCLUSION: Descriptive follow-up data suggest that PTSD may manifest itself >6 months after a traumatic event, delayed-onset PTSD most often, if not always, is preceded by sub-threshold PTSD symptoms, and a higher proportion of PTSD cases are delayed among professional groups. Contextual factors and biased recall may inflate reporting of PTSD and a cautious interpretation of prevalence rates seems prudent.

Effort reward imbalance, and salivary cortisol in the morning.

BACKGROUND: Effort reward imbalance (ERI) is suggested to increase risk for stress and is hypothesized to increase cortisol levels, especially the awakening cortisol response, ACR. METHODS: In 2006 and 2008, 480 individuals collected saliva samples at awakening and 30 min post-awakening. Mixed effects models with subject as a random effect and appropriate covariates were used to evaluate associations between the Effort Reward Model, and salivary cortisol at awakening (S0), and ACR. RESULTS: ERI was negatively and significantly associated with S0 for women and positively associated with ACR. S0 and ACR increased significantly from 2006 to 2008. CONCLUSION: ERI was significantly associated with cortisol levels at awakening (inverse association) for women, and positively associated with ACR. The population experienced a significant increase in morning cortisol levels and ACR from 2006 to 2008, which may originate in a re-organization of the included work places.

Long-term effects of psychosocial factors of home and work on biomarkers of stress.

INTRODUCTION: The current study analyzed the relationship between psychosocial factors measured at baseline and heart rate variability (HRV) and salivary cortisol measured at baseline and again, six years later. METHODS: In 2002 and 2008, measurements of HRV and salivary cortisol at three time points were obtained from 70 healthy participants (48 women and 22 men). The associations between the psychosocial factors measured in 2002 and the dependent variables, HRV and salivary cortisol measured in 2002 and 2008, were examined using a series of repeated measures ANCOVAs. The dependent variables were as follows: the logarithmically transformed levels of total power (LnTP), high frequency power (LnHF), the ratio between low and high frequency power (LnLF/HF) and salivary cortisol (LnCortisol). RESULTS: For women, high social status was associated with high LnTP, high LnHF, and low LnLF/HF. In work, lack of control was associated with low LnTP, and lack of support was associated with an increased LnLF/HF ratio. For men, high social status was associated with low LnTP, low LnHF and high LnCortisol. Greater number of hours spent doing housework was associated with both low LnLF/HF and low LnCortisol, whereas a large imbalance between effort and reward was associated with low LnTP and high LnCortisol. CONCLUSION: Despite the small sample size, this study demonstrated that psychosocial factors impact levels of activity in the allostatic systems.

Effort reward imbalance is associated with vagal withdrawal in Danish public sector employees.

OBJECTIVES: The current study analyzed the relationship between psychosocial work environment assessed by the Effort Reward Imbalance Model (ERI-model) and heart rate variability (HRV) measured at baseline and again, two years later, as this relationship is scarcely covered by the literature. METHODS: Measurements of HRV during seated rest were obtained from 231 public sector employees. The associations between the ERI-model, and HRV were examined using a series of mixed effects models. The dependent variables were the logarithmically transformed levels of HRV-measures. Gender and year of measurement were included as factors, whereas age, and time of measurement were included as covariates. Subject was included as a random effect. RESULTS: Effort and effort reward imbalance were positively associated with heart rate and the ratio between low frequency (LF) and high frequency power (HF) and negatively associated with total power (TP) and HF. Reward was positively associated with TP. CONCLUSION: Adverse psychosocial work environment according to the ERI-model was associated with HRV, especially in the form of vagal withdrawal and most pronounced in women.

Psychosocial factors at home and at work and four-year progression in intima media thickness.

This study analyzed the relationship between psychosocial factors and progression in intima media thickness (IMT). In 1998 and 2002, 95 healthy participants underwent a clinical examination, including ultrasound of the arteria carotis communis (ACC). IMT progression in women was 0.033 mm/year (SD=0.033) and in men 0.048 mm/year (SD=0.033). For cohabiting women as opposed to single women, the means for total IMT progression over the 4 years were, respectively, 0.137 (SE=0.019) and 0.016 (SE=0.048) mm. For women with above average as opposed to below average mean scores of effort, IMT progression were 0.149 (SE=0.026) and 0.098 (SE=0.024) mm, respectively. For men without children as opposed to men with children, mean scores for IMT progression were 0.231 (SE=0.029) and 0.137 (SE=0.028) mm, respectively. For men above average as opposed to those below average, scores of effort-reward imbalance IMT progression were 0.216 (SE=0.030) and 0.155 (SE=0.027) mm, respectively. Adjustment for confounders did not change the results significantly. We found that psychosocial factors were independent significant predictors of IMT progression. The associations were different between the genders.