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This study evaluates the impact of the COVID-19 pandemic on healthcare workers in Argentina, during the second wave in 2021. The aim is to assess stress and burnout, incorporating the assessment of hair cortisol levels as a biomarker of chronic stress. A total of 496 healthcare workers from three different hospitals were included in this study. Two of these hospitals depend on the Buenos Aires City Ministry of Health and the third hospital belongs to Buenos Aires University. Hair samples were obtained using scissors from the posterior vertex, as close to the scalp as possible. Each sample was weighed, and cortisol was extracted and then measured using an automated chemiluminescent method. Notably, 10% of the population exhibited hair cortisol levels above 128 pg/mg. Associations were found between high hair cortisol levels and age, workload, emotional exhaustion, and depersonalization. In addition, burnout, identified in 11% of participants, correlated with higher perceived stress and lower social support. Binary logistic regression revealed associations between burnout and perceived stress, and age. Finally, mediation analysis showed depersonalization as a mediating variable in the relationship between hair cortisol concentration and emotional exhaustion. In conclusion, this study highlights the complex relationships between stress, cortisol levels, and burnout. Prioritizing interventions and research is essential to support the well-being of frontline healthcare professionals, ensuring their resilience during challenging times., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: Hair cortisol concentration (HCC) indicates chronic stress exposure, which is a risk factor in the pathogenesis of burnout and depression. However, findings on HCC are inconsistent. Similarly, intervention studies show mixed effects on HCC. The present study aimed to shed light on these inconsistencies, by additionally considering also hair cortisone., Methods: Twenty-five patients with a burnout-related depressive disorder receiving a multimodal inpatient treatment for clinical burnout and 17 matched healthy controls participated in this study. All participants provided 1 cm long hair samples at the beginning and end of the treatment. HCC and hair cortisone levels (HCNC) were determined. Meteorological data and duration of sick leave were considered as potential covariates. Burnout and depression were assessed with self-ratings, the latter also with examiner ratings., Results: There were no significant group differences in glucocorticoid levels. Treatment led to a decrease in both depression severity and hair glucocorticoid concentration in inpatients, while lower HCNC in particular predicted a greater reduction in depression severity. Moreover, meteorological data and the duration of sick leave were also found to have an effect on hair glucocorticoid concentrations., Conclusions: These results suggest that multimodal inpatient treatment of clinical burnout considerably reduced stress on both a psychological and biological level. In parallel, hair glucocorticoids appear to be sensitive biomarkers for the evaluation of treatment success and prediction. Examining both HCC and HCNC in intervention studies may provide clearer results than the usual examination of HCC alone.

Background: Working conditions in the age of digitalization harbor risks for chronic stress and burnout. However, real-world investigations into biological effects of technostress, that is stress in the context of digital technology use, are sparse. This study prospectively assessed associations between technostress, general work stress, burnout symptoms, hair cortisol, and chronic low-grade inflammation., Methods: Hospital employees (N = 238, 182 females, M age  = 28.5 years) participated in a prospective cohort study with two follow-ups six months apart (T2, T3). Participants answered standardized questionnaires on general job strain (job demand-control ratio), technostressors (work interruptions, multitasking, information overload), burnout symptoms (exhaustion, mental distance), and relevant confounders. Moreover, they provided capillary blood samples for C-reactive protein (CRP) and hair strands for hair cortisol concentration (HCC) analysis. Structural equation modelling was performed., Results: The factorial structure of survey measures was confirmed. Burnout symptoms (M T2  = 2.17, M T3  = 2.33) and HCC (M T2  = 4.79, M T3  = 9.56; pg/mg) increased over time, CRP did not (M T2  = 1.15, M T3  = 1.21; mg/L). Adjusted path models showed that technostress was negatively associated with HCC (β = -0.16, p =.003), but not with burnout and CRP. General work stress in contrast, was not significantly associated with burnout, HCC or CRP. Furthermore, there were reciprocal effects of CRP on HCC (β = 0.28, p =.001) and of HCC on CRP (β = -0.10, p ≤.001). Associations were robust in additional analyses including further confounders., Conclusion: This is the first study on prospective effects of technostress on employees' endocrine and inflammatory systems. Results suggest differential effects of technostress on the hypothalamic-pituitary-adrenocortical axis activity. Given its key role for long-term health, the findings have important implications for occupational health and safety in digitalized work environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In the critical context of COVID-19 pandemic, healthcare workers are on the front line, participating directly in the care, diagnosis, and treatment of patients with COVID-19. This exposes them to a higher risk of developing chronic stress, psychological distress, and any other mental health symptoms., Objective: to evaluate stress and burnout in a health workers population and, in addition, to measure hair cortisol concentration as a current biomarker of stress., Materials and Methods: 234 health workers from Hospital de Clínicas "José de San Martín", Buenos Aires University, were included in this study. In this population hair samples were obtained from the posterior vertex as close to the scalp as possible and the individuals completed the following surveys: perceived stress, social support, burnout scale, life event scale, and sociodemographic data. Hair cortisol was measured by an automated chemiluminescent method. The studied population was divided into three groups considering those individuals below the healthy reference sample range (< 40 pg/mg hair), within the healthy reference range (40-128 pg/mg hair) and above the reference range (> 128 pg/mg hair). This study used a transversal and observational design., Results: Our results show that 40% of the studied population presented hair cortisol values outside of the healthy reference range. In the whole studied population, a direct correlation was found between hair cortisol concentration and perceived stress as well as between hair cortisol concentration and the emotional exhaustion component of burnout (r = 0.142, p = 0.030; r = 0.143, p = 0.029, respectively). 12% of the studied population showed Burnout (52% doctors and residents, 19% nurses, 19% administrative personnel). Higher values in hair cortisol levels were found in the group with burnout versus individuals without burnout (p = 0.034). Finally, a mediation analysis was performed, finding that depersonalization is a mediating variable in the relationship between self-perceived stress and hair cortisol level (F = 4.86, p = 0.0086; indirect effect IC: 0.0987-1.8840)., Conclusion: This is the first study in which a stress biomarker such as hair cortisol is evaluated in this population and in this context. Healthcare workers are subjected to increased levels of stress and burnout. High depersonalization, emotional exhaustion, and decreased personal sense of accomplishment characterize this population. It is the responsibility of the health authorities to implement strategies to manage this psychological emergency., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Medical profession is a stress factor for the development of burnout, symptoms of anxiety and depression as a result of 24-hour work, delayed work-life balance gratification and challenges associated with patient care., Aim: This study aimed to verify the rates of burnout, anxiety, and depression presented by health professionals working 24-hour shifts under emergency conditions. Saliva cortisol and glycated hemoglobin were also studied as stress-related biomarkers., Materials and Methods: Ninety-five medical professionals - physicians, biologists, chemists, and laboratory technicians were compared to a control group working outside medicine. Burnout was measured by the Maslach Burnout Inventory. Anxiety and depression were measured by the State-Trait Anxiety Inventory and the Zung Depression Scale. Salivary cortisol and glycated hemoglobin were analyzed by the immunoassay methods., Results: The level of burnout in the subscale of emotional exhaustion was high in 95.6% of medical professionals. In the subscale of personal accomplishment, 100% had high scores. Regarding the State-Trait Anxiety Inventory, 22.2% and 68.9% of the medical specialists showed a positive score (≥40) for S-anxiety and T-anxiety scale, respectively. 11.1% indicated greater anxiety (score ≥ 55) for T-anxiety. In relation to the depression scale, 31.1% had mildly depressive states and 8.9% had moderately depressive states. Participants with a high level of emotional exhaustion presented higher results for saliva cortisol and glycated hemoglobin compared to the control group. A significant positive correlation existed between the two dimensions - emotional exhaustion and depression (r=0.683, p<0.01)., Conclusions: Our study may be relevant for further research in order to decrease the negative aspects of professional stress., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite the rapid increase of reports of exhaustion syndrome (ES) due to daily occupational stress, the mechanisms underlying ES are unknown. We used voxel-based 1H-MR spectroscopy to examine the potential role of glutamate in this condition. The levels of glutamate were found to be elevated among ES patients (n = 30, 16 females) compared with controls (n = 31, 15 females). Notably, this increase was detected only in the anterior cingulate and mesial prefrontal cortex (ACC/mPFC), and the glutamate levels were linearly correlated with the degree of perceived stress. Furthermore, there was a sex by group interaction, as the glutamate elevation was present only in female patients. Female but not male ES patients also showed an increase in N-acetyl aspartate (NAA) levels in the amygdala. No group differences were detected in glutamine concentration (also measured). These data show the key role of glutamate in stress-related neuronal signaling and the specific roles of the amygdala and ACC/mPFC. The data extend previous reports about the neurochemical basis of stress and identify a potential neural marker and mediator of ES due to occupational stress. The observation of specific sex differences provides a tentative explanation to the well-known female predominance in stress-related psychopathology., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To avoid methodological biases, psychoneuroendocrine studies have generally excluded psychotropic medication users. In workplace stress research, this has limited our ability to understand how psychotropic medication use affects many stress-related measures of interest. In this exploratory study, the effects of psychotropic medication use on stress physiology, occupational stress, and mental health were measured in a sample of healthy adult psychiatric hospital workers (N = 203, 70 % women). Diurnal cortisol was assessed on two non-consecutive work-days at five time-points (e.g., awakening, thirty minutes after awakening, 2 P M, 4 P M and bedtime). Cortisol reactivity was assessed by exposing participants to the Trier Social Stress Test. An allostatic load index was constructed using 19 neuroendocrine, immune, cardiovascular, and metabolic biomarkers. Occupational stress (e.g., job strain, effort-reward imbalance) and psychiatric symptoms (e.g., depression, burnout) were assessed with well-validated self-reports. Results showed that psychotropic medication use had no significant effects on diurnal cortisol profiles; however, psychotropic users had significantly decreased cortisol reactivity to the Trier Social Stress Test and higher allostatic load. Psychotropic users also had decreased effort-reward imbalance, but not job strain. Depressive symptoms did not differ between psychotropic medications users and non-users; however, burnout symptoms were higher among psychotropic medication users than non-users. Taken together, our findings do not warrant the systematic exclusion of psychotropic medication users from psychoneuroendocrine studies if insights into individual differences are sought among workers and other populations exposed to elevated stress., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Chronic stress experienced at work is considered a major health challenge for modern societies. In fact there is ample evidence that deleterious work environments, based on high efforts in relation to few rewards, substantially augment the risk for a number of highly prevalent diseases (e.g. ischemic heart disease, stroke). One potential pathway mediating these associations involves the stress-related activation of the hypothalamus-pituitary-adrenocortical (HPA) axis with proceeding alterations in the secretion of its main effector hormone cortisol. In this study we assessed a prospective, two-year effect of effort-reward imbalance (ERI) on cortisol secretion, based on a sub sample (N = 150; mean ± SD age: 42.4 ± 11.1; 84.0% female) of the ongoing Dresden Burnout Study (DBS). The provided ERI measures were collected as part of the online baseline and first follow up assessment. Further, cortisol secretion patterns over prolonged periods of time were evaluated in three consecutive years of laboratory baseline and follow up visits. Our findings suggest prospective associations between ERI and cortisol, indicating a blunted cortisol secretion in response to long-term work stress (p < 0.001). Given the regulatory properties of cortisol on various central and peripheral target tissues (e.g. cardiovascular system, liver, adipose tissue), a long-term decrease of cortisol availability can be hypothesized to cause multiple health-challenging consequences. Based on our findings, providing work environments where high efforts are always linked with high rewards have to be considered an important issue for employees health., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Growth factors, such as vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and neurotrophic factors, including brain-derived neurotophic factor (BDNF), have attracted attention in studies of the biological effects of long-term stress exposure due to their neuroprotective roles. This study investigated whether circulating levels of EGF, VEGF and BDNF were altered in individuals with stress-related exhaustion disorder. Forty patients diagnosed with exhaustion disorder and 40 healthy subjects (50% women) provided fasting blood samples for analysis of EGF, VEGF, and BDNF in plasma. We found significantly lower levels of EGF, VEGF, and BDNF in patients with ED compared to healthy controls. This pattern was seen in both male and female patients. Given the important roles of BDNF and VEGF for brain plasticity and neurogenesis, decreased levels after long-term stress exposure could indicate increased risk of neuronal damage and cognitive impairments in this patient group., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Backgrounds: The present study was designed to clarify the mutual association of job burnout and insomnia and to detect the mediating effects of hair cortisol on that association., Methods: In all, 68 female employees were recruited for the study from one secondary and one tertiary hospital between October 2018 and November 2018 in Beijing. Participants completed a questionnaire for the collection of demographic data and standardized measures for burnout and insomnia. Hair sample collection and anthropometric measurements were performed at the same time., Results: Median hair cortisol concentration (HCC) was 5.89 ng/g hair (interquartile range = 2.20-10.74). And ages are between 22 and 51 years old (32.50 ± 6.13), among which 22 were below 30 years, 20 were between 30 and 35 years, and 26 were over 35 years. A majority of Pearson's coefficients were significant, with the exception of that for the correlation between personal accomplishment and HCC or depersonalization. Significant mutual correlations were shown between burnout dimensions and insomnia directly. HCC acted as a mediator in the pathway from emotional exhaustion, depersonalization to insomnia; and no significant mediating effect of HCC in the pathway from insomnia to burnout was found., Conclusions: Job burnout may directly or indirectly (through chronically elevated cortisol) increase insomnia risk, whereas insomnia probably promotes burnout. Prospective studies involving different body systems and a larger sample size should be performed to further identify the mechanisms underlying the associations between burnout and insomnia among the working population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Burnout symptomatology is associated with various negative health consequences; however, the mechanisms underlying these associations remain unclear. One potential pathway involves alterations in the acute stress response. The aims of the present study were to examine burnout-associated alterations in stress-reactivity patterns, during a standardized social stressor compared to a control condition, as well as to examine whether effects associated with greater burnout symptomatology were distinct from other, conceptually overlapping indicators of chronic stress (i.e. depressive symptomatology and elevated hair cortisol concentration [HCC])., Materials and Methods: In a randomized two-factor design a total of 70 employed males with varying burnout symptoms but without evidence of physical or psychiatric disease were exposed to the Trier Social Stress Test for Groups (TSST-G) or a non-stressful control condition. Acute stress reactivity was assessed using self-report stress measures and non-invasive biomarkers. Associations among acute stress reactivity, burnout and depressive symptoms (assessed with self-report measures), as well as HCC were analysed using repeated measure ANCOVAs and moderation analysis., Results: Burnout symptomatology was associated with elevated stress perception independent of the experimental condition. In addition, depressive symptomatology was associated with enhanced anticipatory appraisal, whereas HCC was not related to any subjective stress measure. On a physiological level, burnout and depressive symptomatology, as well as HCC were associated with a pattern of blunted cardiovascular reactivity, however the timing of this effect varied., Conclusion: Our results indicate burnout-associated modulations in stress reactivity, which diverge, at least partly, from other indicators of chronic stress., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective The aim of the present study was to investigate the relationship between job burnout and neurotransmitter levels in medical staff. Methods A total of 80 medical staff were enrolled in the study and assessed for occupational burnout using the Maslach Burnout Inventory - General Survey (MBI-GS). The levels of neurotransmitters in the cerebral cortex were analysed using an SP03 encephalofluctuograph. Results The levels of the neurotransmitters γ-aminobutyric acid, 5-hydroxytryptamine (5-HT), norepinephrine (NE), glutamate, acetylcholine (Achl) and dopamine (DA) were significantly lower in men than in women. Medical staff with lower levels of exhaustion had significantly higher neurotransmitter levels than staff with moderate levels of exhaustion. However, there was no significant interaction between sex and exhaustion on neurotransmitter levels. Canonical correlation showed that exhaustion was positively associated with 5-HT and DA, but negatively associated with NE and Achl, regardless of age and sex. Conclusion Neurotransmitter levels in the cerebral cortex were associated with job-related burnout in medical staff. The findings suggest that long-term job-related burnout may lead to behavioural and psychiatric disorders.

Objective: Occupational/mental stressors, which may be evaluated with measurements of salivary cortisol concentrations, affect the endothelial function and has implications on cardiovascular health. Nitric oxide (NO) is known to have an important role in cardiac function and may also be assessed in the saliva, but its participation in physiological responses to hypothalamic-pituitary-adrenal (HPA) axis stimulation is still not completely understood. The aim of the present study was to test the hypothesis that salivary NO (as nitrite) and cortisol concentrations in school teachers vary throughout the academic year., Methods: Saliva samples were collected from 13 teachers distributed across five secondary schools. The samples were collected at 6:30 a.m., 11:30 a.m., and 5:30 p.m. in the months of March, July, and December. Salivary cortisol levels were measured by enzyme immunoassay (EIA), and salivary NO concentration was determined by the quantification of nitrite. The area under the curve in relation to ground (AUC) was calculated to assess the cortisol and nitrite concentrations throughout the day., Results: No significant changes were observed in cortisol or nitrite concentrations across the three periods of the school year, while cortisol and nitrite levels showed a low positive and significant correlation (r=0.3455, p=0.0336)., Conclusion: The results suggest that changes in salivary cortisol levels are accompanied by changes in salivary nitrite levels. This is the first time that such association has been demonstrated. These results encourage further studies aimed to confirm the importance of salivary NO measurement in relation to occupational stress and cardiovascular health.

Background: This supplement registry study evaluated the effect of supplementation with Robuvit® on the burnout syndrome (BOS) of patients with significant fatigue and high oxidative stress. Robuvit® (French oak wood extract) is a standardized supplement, effective in treating chronic fatigue syndrome (CFS), post-traumatic stress disorder (PTSD) and convalescence., Methods: A group of 108 subjects with BOS, consisting of a subgroup of 42 young surgeons in training and a subgroup of 66 managers, were studied. Subjects followed a standard management (SM); one half of the subjects received 300 mg/day of Robuvit® for 4 weeks in addition to SM., Results: Robuvit® was (P<0.05) more effective compared to SM in improving parameters evaluated with the aid of Maslach Burnout Inventory: dealing with patients problems, improving the relationship with patients, decreasing emotional drainage and intolerance (P<0.05). The feeling of a positive influence improved. The decrease in strain from interactions at work, the decrease in the lack of care feeling, the improved levels in interest were all positively affected with Robuvit (P<0.05) in comparison with SM. The need for giving up decreased, the level of satisfaction improved and the regrets for being in the profession decreased. BOS symptoms were positively affected by the supplement (P<0.05). Oxidative stress (388;24 Carr Units decreased to 344;22 with Robuvit®; P<0.05), SM had no influence on oxidative stress. Robuvit® was also more effective in professionals with burnout syndrome than the SM only in in decreasing emotional drainage, fatigue and intolerance (P<0.05). Robuvit® significantly improved the feeling of having a positive influence (P<0.05). Also, Robuvit® significantly decreased the strain resulting from interactions at work and improved the care for colleagues/customers (P<0.05). Interest and enthusiasm were significantly increased in subjects taking Robuvit® in comparison with controls with standard management alone (P<0.05). The mean score of the desire to give up was decreased with Robuvit® in comparison with SM (P<0.05) and job satisfaction was significantly improved (P<0.05). The feeling of regrets of being in the profession was significantly reduced with the supplement in comparison to SM (P<0.05). Robuvit® reduced oxidative stress (P<0.05) from 397;33 to 323;29 Carr Units in comparison with a low decrease with SM (from 396;19 vs. 378;27) at 4 weeks., Conclusions: In conclusion, in this registry study on BOS, Robuvit® by controlling fatigue (the primary symptom) and oxidative stress, relieves the most important 'symptoms' associated with BOS. The effects are comparable in young surgeons not accustomed to stress, as well as in professionals in management positions who are used to control stress.

ABSTRACTObjective:A high incidence of burnout has been reported in health professionals working in palliative care units. Our present study aims to determine whether there are differences in the secretion of salivary cortisol between palliative care unit health professionals with and without burnout, and to elucidate whether there is a relationship between burnout syndrome and perceived stress and psychopathological status in this population., Method: A total of 69 health professionals who met the inclusion criteria participated in our study, including physicians, nurses, and nursing assistants. Some 58 were women (M = 29.65 years, SD = 8.64) and 11 men (M = 35.67 years, SD = 11.90). The level of daily cortisol was registered in six measurements taken over the course of a workday. Burnout syndrome was evaluated with the Maslach Burnout Inventory-Human Services Survey (MBI-HSS), the level of perceived stress was measured using the Perceived Stress Scale, and psychopathological status was gauged using the SCL-90-R Symptoms Inventory., Results: There were statistically significant differences in secretion of cortisol in professionals with high scores on a single subscale of the MBI-HSS [F(3.5) = 2.48, p < 0.03]. This effect was observed 15-30 minutes after waking up (p < 0.01) and at bedtime (p < 0.06). Moreover, the professionals with burnout showed higher scores on the psychopathology and stress subscales than professionals without it., Significance of Results: A higher score in any dimension of the burnout syndrome in palliative care unit health professionals seems to be related to several physiological and psychological parameters. These findings may be relevant for further development of our understanding of the relationship between levels of burnout and cortisol secretion in the health workers in these units.

Burnout is a syndrome with negative impact on cognitive performance and mood as a consequence of long-term stress at work. It is further associated with increased risk for mental and physical diseases. One potential pathway to mediate chronic work-stress and adverse health conditions in burnout is through alterations in long-term glucocorticoid secretion. Here, we present cross-sectional data on hair cortisol/cortisone (hairF/hairE) concentrations and burnout from a population-based sample of the Dresden Burnout Study (DBS; N=314 hair samples). Burnout symptoms (emotional exhaustion, cynical attitudes toward work, and reduced efficacy) were assessed with the Maslach Burnout Inventory-General Survey (MBI-GS). To control for potential confounds, depressivity was as well assessed using the Patient Health Questionnaire (PHQ-9) screening instrument for major depression. The present findings indicate specific hypercortisolism in participants who suffer from burnout. No significant associations were found between depressivity and hairF/hairE., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The purpose was to reexamine cognitive performance and cortisol levels of initial clinical burnout patients, non-clinical burnout individuals, and healthy controls. After 1.5-years of the initial measurement, clinical burnout patients showed a reduction of burnout symptoms and general physical and psychological complaints, but these were still elevated compared with controls. Nonetheless, they continued to report cognitive problems and still showed a minor impaired cognitive test performance. However, they no longer reported larger subjective costs associated with cognitive test performance and their cortisol awakening response (CAR) returned to a normal level. Compared with controls, non-clinical burnout individuals still reported the same, elevated, level of burnout symptoms, general physical and psychological complaints, and cognitive problems. Their cognitive test performance and associated subjective costs remained normal. However, they seemed to continue to display a lowered CAR. To conclude, after 1.5-years, clinical burnout patients got better, but not 'well', and non-clinical burnout individuals remained not 'well'., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Although the relationship between burnout and cortisol levels has been examined in previous studies, the results are mixed. By adopting a design in which we attempted to overcome important limitations of earlier research, the purpose of the present study was to improve the understanding of the biological underpinnings of burnout and to further the knowledge about the relationship between burnout and cortisol., Methods: A clinical burnout patient group (n =32), a non-clinical burnout group (n =29), and a healthy control group (n =30) were compared on burnout symptoms, physical and psychological complaints, and on cortisol levels. In order to examine a broad range of cortisol indices, including different measures of the cortisol awakening response (CAR) and several day-curve measures, salivary cortisol was collected six times a day during two consecutive non-workdays., Results: As expected, the clinical burnout group reported more burnout symptoms, and physical and psychological complaints than the non-clinical burnout group, which in turn reported more burnout symptoms and physical and psychological complaints than the healthy control group. With regard to cortisol levels, we found that until 30 min after awakening, the CAR of both the clinical and the non-clinical burnout group was lower compared with the healthy control group. Furthermore, there was some evidence that the decline of cortisol during the day was smaller in the non-clinical burnout group than in the healthy control group., Conclusion: The results of the present study provide support for lowered cortisol in both clinical and non-clinical burnout., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To determine whether a workplace stress-reduction intervention decreases reactivity to stress among personnel exposed to a highly stressful occupational environment., Methods: Personnel from a surgical intensive care unit were randomized to a stress-reduction intervention or a waitlist control group. The 8-week group mindfulness-based intervention included mindfulness, gentle yoga, and music. Psychological and biological markers of stress were measured 1 week before and 1 week after the intervention., Results: Levels of salivary α-amylase, an index of sympathetic activation, were significantly decreased between the first and second assessments in the intervention group with no changes in the control group. There was a positive correlation between salivary α-amylase levels and burnout scores., Conclusions: These data suggest that this type of intervention could decrease not only reactivity to stress but also the risk of burnout.

The current study assessed which specific burnout symptoms were most predictive of distinct diurnal cortisol profiles. Participants included 401 day-shift workers employed in a random sampling of 34 Canadian workplaces. The 16-item Maslach Burnout Inventory was used to extract burnout sub-scales that included emotional exhaustion, cynicism, professional inefficacy, as well as a global burnout average. Consenting workers provided five saliva samples a day (awaking, 30 min after awaking, 1,400 h, 1,600 h, and bedtime) repeated three times over the course of a week (Saturday, Tuesday, Thursday) to capture workday and non-workday variations. Multilevel regression models were estimated from cortisol measurements at each occasion within a day at level-1, workers at level-2, and workplaces at level-3. Multilevel regression analyses found that emotional exhaustion and a global burnout showed the strongest and consistent negative associations to cortisol in the afternoon and evening. In a separate analysis using regression coefficients, emotional exhaustion and a global burnout average were associated with low cortisol levels 30 min upon awakening. By contrast, professional inefficacy was associated only with lower bedtime cortisol. No associations were detected for cynicism and sex did not emerge as a moderator in secondary analyses. Our findings are discussed in a theoretical framework postulating different pathophysiological stages of burnout development. Specifically, professional inefficacy may be the earliest warning signal culminating with emotional exhaustion that may dampen diurnal cortisol levels., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Currently, a considerable amount of work stress is present in school teachers, one of the occupational groups with the highest levels of job strain and burnout. As chronic stress produces significant modifications in emotional adjustment and neuroendocrine functioning, we aimed to investigate the role of these work stress constructs in the endocrine and mood responses of a group of female teachers during two working days (WD) at different moments in the academic year. We studied mood as well as levels of cortisol and testosterone, representative of a predominant catabolic or anabolic balance. Our results showed that higher "control" was associated with higher positive mood (p = .028 on WD1 and p = .057 on WD2) and salivary testosterone (Tsal) (p = .022 on WD1), whereas "demands" and "total job strain" were related to negative mood (p = .011 and p = .015, respectively). Participants with higher scores on "total burnout" and "emotional exhaustion" also had higher negative mood (p < .05 in all cases). Depersonalization correlated positively with negative mood (p = .019 and p = .006 on WD1 and WD2, respectively). Finally, personal accomplishment showed an inverse relationship with negative mood (p = .038 on WD2). These results are useful for job risk prevention and interventions that should focus on the control dimension of the job strain questionnaire and on personal accomplishment from the burnout scale.

Work related psychosocial stress can be accompanied by so called burnout syndrome with symptoms of mental exhaustion, physical fatigue, and cognitive dysfunction. Underlying mechanisms for acquiring burnout syndrome are not clear. Animal studies show that chronic stress is associated with altered release of GABA-A receptor modulating steroids (GAMS), altered composition of the GABA-A receptor and altered sensitivity to GAMS. In the present study we investigated if such changes occur in women with burnout syndrome. We further asked whether flumazenil (a benzodiazepine antagonist, but with positive modulating effects on GABA-A receptors with altered subunit composition) can block the effect of the GAMS allopregnanolone. Ten women with occupational psychosocial stress and burnout syndrome were compared with twelve healthy controls in an experimental setting. Saccadic eye velocity (SEV) was measured after an injection of allopregnanolone, followed by an injection of flumazenil and a second injection of allopregnanolone. The sensitivity to allopregnanolone was significantly higher in the patients compared to controls after the first injection (p=0.04) and the difference increased when the response per allopregnanolone concentration unit was compared (p=0.006). Following the flumazenil injection the burnout patients (p=0.016), but not controls, showed a decrease in SEV and flumazenil acted like a positive modulator that is agonistic. There was no significant difference between the groups after second allopregnanolone injection. In conclusion, patients with work related psychosocial stress and burnout syndrome show a different response to GABA-A receptor modulators than controls suggesting a changed GABA-A receptor function in these patients. More precisely we hypothesize that the α4 and delta subunits are up-regulated elevating the responsiveness to allopregnanolone and change the effect of flumazenil, which provides a potential explanation to the burnout syndrome. Flumazenil does not block the effect of allopregnanolone., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to review recent medical findings related to burnout, its diagnosis, treatment, characteristic pathophysiological features, and preventive measures., Materials and Methods: A systematic review of the scientific literature in PubMed/Medline was performed. The most recent and important findings were reported., Results: Burnout was found to be a risk factor for myocardial infarction and coronary heart disease. It was also related to reduced fibrinolytic capacity, decreased capacity to cope with stress and hypothalamic-pituitary-adrenal (HPA) axis hypoactivity. Severe burnout symptoms are associated with a lower level or smaller increase of the cortisol awakening response (CAR), higher dehydroepiandrosterone-sulphate (DHEAS) levels, lower cortisol/DHEAS ratios and stronger suppression as measured by the dexamethasone suppression test (DST). More and more literature works suggest that the evaluation of the HPA axis should be brought to the attention of primary care physicians. There is no universal agreement on specific treatment and diagnostic measures to evaluate the wide range of HPA axis disorders. The cost-effective evaluation of adrenal hormones via saliva samples by a primary care physician may significantly alter the course of therapy in numerous chronic disease patients. Psychiatric disorders may have similar symptoms, but they have distinctive hormonal profiles. Having burnout recognized as a medical condition would help in differentiating burnout from similar clinical syndromes, such as depression or anxiety, and provide appropriate treatment to burnout patients. Proper treatment is essential for a fast and full recovery., Conclusion: Chronic stress-related disorders often fall outside the category of a "true" disease and are often treated as depression or not treated at all. The evaluation of adrenal hormones via saliva samples helps to predict burnout. Burnout screening techniques, dietary and nutritional guidelines and lifestyle changes for supporting the HPA function need to be developed. The presented material includes hormonal, dietary, and pharmaceutical perspectives.

Anesthesiology is a stressful medical profession. While anesthesia in particular has become safer for the patient in the last decades, anesthesiology as a profession represents a medical field in which the professionals are permanently tense. The various reasons for this situation include the fact that anesthesiology is a team profession that requires perfect cooperation with other specialists. It also entails great responsibility for the patient's life, the daily use of "blind" invasive techniques, and last but not least the production pressure that characterizes the activity in the operating room. There are various methods to quantify professional stress and this article emphasizes the place of measurement of salivary cortisol in order to identify those stressful moments that are part of the anesthesiologist's routine activity, in addition to those individuals who are more prone to develop negative aspects of stress. It seems that there is a strong correlation between the high level of salivary cortisol and stressful events during patient management and also a correlation between this level and a high score of implicit job-stress. This reality created the need to look for remedies; some authors recommend a long list of measures to be taken in order to prevent or reduce the magnitude of professional stress. This list includes a continuous self-care attitude, consisting of having a balanced professional and personal life; adequate sleep; avoiding drugs, obesity, and "workaholic" behavior; as well as better use of leisure. Finally, more studies are needed to find out which preventive means may potentially reduce the risk of professional stress among anesthesiologists.

Background: The symptoms of burnout are similar to those of depression on the one hand and chronic fatigue syndrome on the other hand. However, the neuro-endocrine correlates of these two syndromes are the opposite, the former being a hyperfunction of the hypothalamic-hypophysial-cortical axis (HPA) and the latter being a hypofunction of the hpa-axis., Aim: To find out, via a systematic review of the literature, whether burnout is associated with either a hyperfunction or a hypofunction of the HPA-axis., Method: We searched PubMed using the following search terms: 'burnout syndrome and burnout', 'adrenocorticotropic hormone', 'corticotropin releasing factor', 'hypothalamic pituitary adrenal axis' and 'cortisol'. We retrieved 16 original articles en one meta-analysis were included in the study., Results: Functional stress testing showed hypersuppression of the HPA-axis after dexamethasone. Basal cortisol values were found to be less conclusive, although a meta-analysis pointed to a negative association between burnout and cortisol. We did not find any studies that were carried out with the help of physiological, physical or psychological stress factors in burnout., Conclusion: Burnout is associated primarily with a hypofunction of the HPA-axis, which is a neuro-endocrine characteristic of exhaustion, rather than of depression. However, further studies involving functional stress testing are needed in order to map the neuro-endocrine profile fully and to clarify the link with the deregulation of the immune system.

Background: Burnout is a stress state characterized by symptoms of mental exhaustion and physical fatigue, detachment from work, and feelings of diminished competence. Several biomarkers have been tested for association with burnout, but the results are conflicting., Aim: The objective of this review was to identify potential biomarkers for burnout., Methods: We carried out a systematic review of studies comparing biomarkers in individuals with burnout and healthy controls, or individuals with low scores and those with high scores on burnout questionnaires. Literature searches in MEDLINE and EMBASE were performed. We describe biomarkers on which at least three studies were available. Where appropriate, a meta-analysis was carried out., Results: We identified 31 studies on 38 biomarkers involved in the hypothalamus-pituitary-adrenal axis, autonomic nervous system, immune system, metabolic processes, antioxidant defense, hormones, and sleep. At least 3 studies were available for cortisol in saliva and blood, blood pressure, heart rate, cholesterol, dehydroepiandrosterone sulfate, (numbers or activity of) natural killer cells, C-reactive protein, and prolactin. The comparability of studies was limited, due to differences in the methods used to characterize patients and controls, to assess biomarkers, and to control for confounders. Furthermore, burnout was operationalized in different ways. Meta-analyses showed no differences for cortisol awakening response and cortisol awakening response after administration of dexamethasone, cortisol in blood, and blood pressure., Conclusions: No potential biomarkers for burnout were found, largely due to the incomparability of studies. We emphasize the need for a dimensional and longitudinal approach in future research to account for the heterogeneity of burnout., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Studies on HPA axis regulation in burnout revealed heterogeneous results, possibly due to different psychometric and endocrine measurements, heterogeneous samples or small sample sizes. In the present study, the relationship between salivary cortisol during the day (four time points: 0700 h, 1130 h, 1730 h, and 2000 h) and burnout as well as vital exhaustion was investigated in a large sample of 279 nurses. Burnout was measured using the Maslach Burnout Inventory (MBI), which includes scales for emotional exhaustion, depersonalization, and personal accomplishment. A burnout criterion was assumed to be fulfilled, when any of the MBI scales was above the norm. Subjects with two burnout criterions fulfilled (N=18) were characterized by a higher cortisol release over the day compared to those reporting only one criterion (N=77) or no burnout (N=181) (ANOVA, p=.015). On the other hand, subjects who reported high levels of vital exhaustion did not differ from those who did not report signs of vital exhaustion. These findings provide further evidence for HPA axis dysregulation in burnout.

The aim of this study was to investigate the long-term effects of need for recovery from work and trait rumination on saliva cortisol secretion. The sample consisted of 76 white-collar workers, 52 men and 24 women who had previously provided baseline data four years earlier and volunteered to participate in the present study. In the present study, saliva cortisol secretion was measured over seven consecutive days, on awakening, and at 10 p.m. No relationships were found between the independent variables and morning saliva cortisol levels. High trait rumination at baseline, however, was significantly related to higher evening cortisol levels for both women and men. Baseline need for recovery from work was strongly related to evening cortisol secretion for women, but in the opposite direction than expected. The present results add to the small but equivocal body of literature that has examined the long-term effects of work strain on cortisol secretion.

Objective: This review aimed to present an overview of neurobiological research on the etiology of burnout and to evaluate the proposed arguments., Method: A retrospective literature review of the relevant studies conducted within the last 17 years. For this purpose a literature search was conducted via internet-based search engines, including PubMed, Science-Direct, Medline, GoogleScholar, ULAKBIM Turkish Medicine Index, and Turkish Psychiatry Index, using the key words, burnout, cortisol, the hypothalamus-pituitary-adrenal gland (HPA)-axis, stress, neurobiology, neurogenesis, BDNF, immunology, and etiology, in different combinations., Results: The pioneering studies that focused on the relationship between burnout and dysregulation of the HPA-axis have yielded inconsistent results. Data from subsequent studies with improved designs suggest there is no HPA-axis dysregulation in burnout, but the results do not lead to more concrete interpretations. There is some evidence of impaired immunity function in burnout as compared with controls. Although there is strong evidence of a relationship between stress and impairment in hippocampal neurogenesis, there is no study of burnout in the field. Data about monoaminergic involvement in burnout, which is one of the probable pathways, is scarce., Conclusion: In future research the essential guidelines for evaluating HPA-axis functioning (i.e. timing of collecting samples from saliva or blood and controlling for possible influencing factors on HPA-axis functioning) in patients clinically diagnosed with burnout should be taken into account, and in addition to the HPA-axis, evaluation of hippocampal neurogenesis, neurotrophins, immunity functioning, and the monoaminergic system will provide more data on the neurobiology of burnout.

Chronic stress is known to affect the HPA axis. The few clinical studies which have been conducted on HPA-axis function in burnout have produced inconsistent results. The etiological relationship between sBDNF and burnout has not yet been studied. The aim of the current study was to investigate the role of BDNF and HPA axis in the neurobiology of burnout. In the current study 37 clinically diagnosed burnout participants were compared with 35 healthy controls in terms of BDNF, HPA axis, burnout symptoms, depression, anxiety and psychosomatic complaints. Basal serum cortisol, sBDNF and cortisol level after 1 mg DST was sampled. We found no significant differences in terms of HPA-axis function (for basal serum cortisol, p=0.592; for cortisol level after 1 mg DST, p=0.921), but we did find lowered sBDNF levels in burnout group (88.66+/-18.15 pg/ml) as compared to healthy controls (102.18+/-20.92 pg/ml) and the difference was statistically significant (p=0.005). Logistic Regression Analysis revealed that emotional exhaustion (p=0.05), depersonalization (p=0.005) and depression (p=0.025) were significantly associated with burnout. sBDNF levels correlated negatively with emotional exhaustion (r=-,268, p=0.026), depersonalization (r=-,333, p=0.005) and correlated positively with competence (r=0.293, p=0.015) sub-scales of burnout inventory. However, there were no significant relationships between cortisol levels and sBDNF levels (r=0.80, p=0.51), depression, anxiety, psychosomatic complaints and burnout inventory. Our results suggest that low BDNF might contribute to the neurobiology of burnout syndrome and it seems to be associated with burnout symptoms including altered mood and cognitive functions.

We analyzed whether burnout and vital exhaustion or job-related chronic stress is associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation in school teachers (N=135; 25-63 years; mean age 46.1+/-9.20 years). Participants collected seven saliva samples (0, 30, 45, and 60 min after awakening, 11a.m., 3 p.m., 8 p.m.) on 2 working days, 1 leisure day, and after pre-medication with 0.25mg dexamethasone (very low-dose dexamethasone suppression test) to assess basal cortisol day profiles and HPA axis negative feedback sensitivity. No associations were found between basal cortisol activity and burnout (Maslach burnout inventory, teacher burnout scale), vital exhaustion (Appels vital exhaustion questionnaire), or any component of Siegrist's effort-reward-imbalance model. However, after dexamethasone higher burnout and vital exhaustion and lower reward were significantly related to stronger cortisol suppression, pointing to altered HPA axis negative feedback sensitivity. Though, all teachers were working and in a good health status, burnout/exhaustion as well as facets of the ERI model appear to be associated with subtle dysregulation, manifested as heightened HPA axis negative feedback although not in basal cortisol day profiles.

Objective: This study attempted to determine the relationship of physiological indices of stress (ie, cortisol and salivary immunoglobulin A) to the job strain and the job demand-control-support models., Methods: A sample of 98 direct-care disability workers completed the Maslach Burnout Inventory and the Job Content Questionnaire. In addition, participants' morning saliva samples were analyzed for cortisol and salivary immunoglobulin A concentration levels., Results: The job strain and job demand-control-support models were tested using structural equation modeling. The job demand-control-support model successfully fitted with the data and was able to predict physiological outcomes, the job strain model did not. The salivary immunoglobulin A scores, in comparison to the cortisol data, were predicted more successfully by these models., Conclusions: Researchers are encouraged to study if different employee groups are at-risk for differing types of stress-related-illness, which may be triggered by occupation-specific stressors and/or physiological reactions.

Several studies have investigated the association between burnout and HPA-axis functioning, but the results are far from consistent. This does not preclude the possibility that within a group of burnout patients a recovery of symptoms in a longitudinal course corresponds to (changes in) cortisol parameters. The latter possibility is tested in the present study before and after treatment, and at follow-up. HPA-axis functioning and burnout complaints were assessed in burned-out participants at baseline (n=74), post-treatment (n=62) and at follow-up (n=53). Multilevel regression analysis was used to test the hypothesis. Burnout complaints were significantly reduced at 8.5 months post-treatment, but there was no further reduction in complaints at follow-up 6.3 months later. Cortisol after awakening, and after dexamethasone intake showed no changes from baseline to post-treatment and follow-up. There was a small decline in cortisol during the day over the longitudinal course. The cortisol level after awakening in the longitudinal course showed significant positive association with the initial exhaustion level, a negative association with the change in the burnout exhaustion score, and a positive association with the change in depression. Although these associations are statistically significant, they only explain a small fraction of the variance in cortisol after awakening between and within persons. This implies that changes at symptom level are hardly related to changes in cortisol functioning, therefore the clinical implications of this finding are limited.

Burnout is presumed to be the result of chronic stress, and chronic stress is known to affect the HPA-axis. To date, studies on HPA-axis functioning in burnout have showed inconsistent results. In the present study, a large sample (n=74) of clinically diagnosed burnout individuals, mostly on sick-leave, were included and compared with 35 healthy controls. Salivary cortisol was sampled on 2 days to determine the cortisol awakening response (CAR) and the day-curve. In addition, the dexamethasone suppression test (DST) was applied to assess the feedback efficacy of the HPA-axis. There were no differences observed in the CAR, day-curve or CAR after DST in the burnout group as compared to a healthy control group. Burnout shows overlap in symptoms with chronic fatigue syndrome (CFS) and depression. Therefore, differential changes in HPA-axis functioning that resemble the hypo-functioning of the HPA-axis in CFS, or rather the hyper-functioning of the HPA-axis in depression, might have obscured the findings. However, no effect of fatigue or depressive mood on HPA-axis functioning was found in the burnout group. We concluded that HPA-axis functioning in clinically diagnosed burnout participants as tested in the present study, seems to be normal.

In this overview, we summarize findings on hypothalamus-pituitary-adrenal (HPA) axis functioning in burned out and (vitally) exhausted though otherwise healthy subjects as well as clinically diagnosed patients. The main focus will be on basal diurnal free cortisol regulation and cortisol responses to acute psychological stress. First, we describe normal HPA axis regulation as well as dysfunction which manifests in hyper- or hypoactivity. We also briefly illustrate three established methods to assess HPA axis activity, reactivity, and feedback functioning, namely the cortisol awakening rise (CAR), Trier Social Stress Test (TSST), and low-dose Dexamethasone Suppression Test (DST). Then, an up-to-date summary of empirical findings on the relationship between burnout, respectively vital exhaustion, and cortisol is provided including field as well as laboratory studies. Finally, we briefly discuss possible methodologically confounders and speculate on underlying mechanisms explaining, at least in part, how burnout and vital exhaustion might relate to disease vulnerability.

The authors' goal was to document baseline pituitary-adrenal hormonal and related metabolic variables in 16 female patients with burnout. Then, following stress management intervention, to compare the changes with an equal number of untreated control subjects. At monthly intervals for 4 mo, 24-h urine samples were obtained for determination of free cortisol excretion. In addition, fasting blood samples were analyzed for levels of cortisol, dehydroepiandrosterone sulfate (DHEAS), ACTH, aldosterone, and catecholamines. Other biochemical measurements included growth hormone, prolactin, insulin, glucose, and lipid components. The Maslach Burnout Inventory, General Health Questionnaire- 28, and Zung depression rating scale were completed on each consecutive visit. The most striking finding was the reduction of urine free-cortisol excretion in the patients compared with controls. Initial urinary free cortisol was significantly lower in the patients (mean +/- SEM = 47.2 +/- 11.0 vs 79.0 +/- 6.8 nmol/L, p = 0.02) and remained significantly reduced at 4 mo (mean +/- SEM = 44.0 +/- 6.1 vs 91.1 +/- 8.8 nmol/L, p = 0.0001). There were no significant changes in the other hormonal and biochemical data. We conclude that there is functional hypocortisolism in burnout, which is not immediately restored on stress management intervention despite clinical and psychological improvement.

We examined an analytical method for urinary vanilmandelic acid (VMA) by high-performance liquid chromatography with electrochemical detection from the viewpoint of practical analysis and application. The sample pretreatment in our method is only the dilution of urine samples with citrate buffer. The calibration curve for VMA was linear within the range 0.2 to 20 ng. The detection limit was 50 pg at a signal-to-noise ratio of 3 and the coefficients of variation were 2.30-4.30%. Variations in the urinary levels of VMA, noradrenaline (NA) and adrenaline (Ad) during and after exercise were investigated for 5 males (mean +/- SD, 42.4 +/- 4.3 years of age). The high levels of urinary NA and Ad during 1 hr exercise rapidly decreased after exercise, whereas urinary VMA increased after exercise rather than during exercise and decreased later. The correlation of the urinary levels of VMA and NA for 71 salesman (mean +/- SD, 40.6 +/- 11.7 years of age) in a field study was significantly positive (r = 0.426, p < 0.001). These results suggest that urinary VMA mostly reflects NA, but the excretion rate of VMA is slower than that of NA.

Objective: The effects of burnout and perceived stress on early morning free cortisol levels after awakening were investigated in a group of teachers. Previous studies revealed that cortisol levels show a significant increase after awakening, with high intraindividual stability., Methods: Sixty-six teachers from local public schools (42 women and 24 men, mean age 42+/-5 years) were asked to sample saliva for cortisol analysis on 3 consecutive days. On each day, cortisol levels were measured at the time of awakening and 15, 30, and 60 minutes thereafter. On the night before the third day, subjects took 0.5 mg dexamethasone orally for testing glucocorticoid feedback inhibition. Burnout and perceived stress were measured by three different questionnaires., Results: Perceived stress correlated with increases of cortisol levels during the first hour after awakening after dexamethasone pretreatment. In addition, teachers scoring high on burnout showed lower overall cortisol secretion on all sampling days, and a higher suppression of cortisol secretion after dexamethasone administration. In the subgroup of teachers with both high levels of perceived stress and high levels of burnout, a lower overall cortisol secretion was observed on the first 2 days, with stronger increases during the first hour after awakening after dexamethasone suppression. This subgroup also showed the lowest self-esteem, the highest external locus of control, and the highest number of somatic complaints., Conclusions: These results demonstrate differential effects of burnout and perceived stress on hypothalamic-pituitary-adrenal axis regulation.