Clinical burnout is not reflected in the cortisol awakening response, the day-curve or the response to a low-dose dexamethasone suppression test

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.     

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.     

Chronic burnout, somatic arousal and elevated salivary cortisol levels

Burnout syndrome, comprised of the symptoms of emotional exhaustion, physical fatigue, and cognitive weariness, is believed to be a result of ineffective coping with enduring stress. This study of 111 nonshift blue-collar workers free of cardiovascular disease (CVD) examined whether chronic burnout is associated with a state of somatic and physiological hyperarousal. Results showed that 37 workers exhibited symptoms of chronic burnout, with symptoms lasting at least 6 months. These workers, compared to those with no burnout symptoms (n=52) or nonchronic burnout symptoms (n=22), had higher levels of tension at work, postwork irritability, more sleep disturbances and complaints of waking up exhausted, and higher cortisol levels during the work day. These results suggest that chronic burnout is associated with heightened somatic arousal and elevated salivary cortisol levels. This may be part of the mechanism underlying the emerging association between burnout and risk of CVD.     

Enhanced cortisol suppression in response to dexamethasone administration in traumatized veterans with and without posttraumatic stress disorder

BACKGROUND: While enhanced cortisol suppression in response to dexamethasone is one of the most consistent biological findings in posttraumatic stress disorder (PTSD), the relative contribution of trauma exposure to this finding remains unclear. METHODS: Assessment of diurnal salivary cortisol levels and 1600 h salivary cortisol before and after oral administration of 0.5mg dexamethasone in veterans with PTSD, veterans without PTSD (trauma controls) and healthy controls. Assessment of 1600 h plasma cortisol, ACTH and corticotrophin binding globulin (CBG) in response to dexamethasone in PTSD patients and trauma controls. RESULTS: Both PTSD patients and trauma controls demonstrated significantly more salivary cortisol suppression compared to healthy controls. Salivary cortisol, plasma cortisol and ACTH suppression as well as CBG levels did not differ between PTSD patients and trauma controls. PTSD patients showed a reduced awakening cortisol response (ACR) compared to healthy controls that correlated significantly with PTSD symptoms. No significant differences were observed in ACR between PTSD patients and trauma controls. CONCLUSIONS: These data suggest that enhanced cortisol suppression to dexamethasone is related to trauma exposure and not specifically to PTSD. The correlation between the ACR and PTSD severity suggests that a flattened ACR may be a result of clinical symptoms.     

Elevated diurnal salivary cortisol in nurses is associated with burnout but not with vital exhaustion

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.     

Women's work stress and cortisol levels: a longitudinal study of the association between the psychosocial work environment and serum cortisol

OBJECTIVE: The aim of the present study was to investigate whether there is an association between serum cortisol and work-related stress, as defined by the demand-control model in a longitudinal design. METHODS: One hundred ten women aged 47-53 years completed a health questionnaire, including the Swedish version of the Job Content Scale, and participated in a psychological interview at baseline and in a follow-up session 2 years later. Morning blood samples were drawn for analyses of cortisol. RESULTS: Multiple stepwise regression analyses and logistic regression analyses showed that work demands and lack of social support were significantly associated with cortisol. CONCLUSIONS: The results of this study showed that negative work characteristics in terms of high demands and low social support contributed significantly to the biological stress levels in middle-aged women. Participation in the study may have served as an intervention, increasing the women's awareness and thus improving their health profiles on follow-up.     

Increased diurnal salivary cortisol in women with borderline personality disorder

Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability in affect regulation, impulse control, interpersonal relationships, and self-image. In previous studies, we have used portable mini-computers to assess the severity of recurrent states of aversive emotional distress and dissociation during ambulatory conditions. Here, we used this approach for the assessment of the hypothalamic–pituitary–adrenal (HPA) axis in patients with BPD. We studied 23 unmedicated female patients with BPD and 24 matched healthy controls. Salivary cortisol was collected from all participants during ambulatory conditions in response to reminders provided by portable mini-computers on 3 consecutive days every 2 h for 14 h after awakening. In addition, cortisol in response to awakening was determined in four 15 min intervals on days 1 and 2. After the last collection of cortisol on the second day, 0.5 mg dexamethasone was administered in order to achieve cortisol suppression on day 3 (low-dose dexamethasone suppression test, DST). Patients with BPD displayed significantly higher salivary cortisol levels than healthy controls as demonstrated by higher total cortisol in response to awakening and higher total daily cortisol levels. There were significantly more non-suppressors of cortisol in the low-dose DST in the patient group when compared to the control group. The ambulatory assessment of saliva cortisol is a suitable approach to study basic parameters of the HPA-axis in patients with BPD. Increased adrenal activity and lowered feedback sensitivity of the HPA-axis may characterise BPD. Further studies have to reveal reasons of heightened adrenal activity in these patients.     

Comparison of solid-phase radioimmunoassay and competitive protein binding method for postdexamethasone cortisol levels in psychiatric patients

Results obtained by competitive protein binding assay (PBA) and a solid-phase radioimmunoassay (RIA) for cortisol were compared in 157 samples from 100 psychiatric patients given a dexamethasone suppression test (DST). Cortisol levels in plasma samples obtained at 8:00 a.m. or 4:00 p.m. the day following 1.0 mg dexamethasone orally at bedtime ranged from 0 to 30 micrograms/dl and correlated closely (r = 0.96). However, RIA gave values that were consistently and significantly lower (average = 8.9%) than those obtained by PBA. When samples were further assayed by a specific RIA for corticosterone, there was a strong correlation between cortisol and corticosterone RIA values (r = 0.79), and corticosterone (7.8% of cortisol levels) accounted for most of the difference between PBA and RIA for cortisol. The relationship between results of the two cortisol assay methods can be expressed (in micrograms/dl) by the equation: RIA = 0.92(PBA) - 0.10, based on findings obtained in a separate analysis of 127 samples with cortisol values in the 0-10 micrograms/dl range, critical to the valid interpretation of the DST in melancholia. A reported criterion of a "positive" DST in psychiatry, of plasma cortisol of greater than or equal to 5.0 micrograms/dl has been suggested by use of a PBA. Use of the present RIA required that this value be adjusted downward, at least to 4.5 micrograms/dl; application of this criterion increased the clinical sensitivity of the DST by 10%. We urge local, independent verification of criteria to define the DST as "positive" in each laboratory and with each method of assay.     

In search of the HPA axis activity in unipolar depression patients with childhood trauma: Combined cortisol awakening response and dexamethasone suppression test

The aim of the present study was to examine the impact of childhood trauma on HPA axis activity both in depression patients and healthy controls in order to determine the role of HPA axis abnormalities in depression and to find the differences in HPA axis functioning that may lead certain individuals more susceptible to the depressogenic effects of childhood trauma. Eighty subjects aged 18–45 years were recruited into four study groups (n = 18, depression patients with childhood trauma exposures, CTE/MDD; n = 17, depression patients without childhood adversity, non-CTE/MDD; n = 23, healthy persons with childhood trauma, CTE/non-MDD; and n = 22, healthy persons without childhood adversity, non-CTE/non-MDD). Each participant collected salivary samples in the morning at four time points: immediately upon awakening, 30, 45, and 60 min after awakening for the assessment of CAR and underwent a 1 mg-dexamethasone suppression test (DST). Regardless of depression, subjects with CTE exhibited an enhanced CAR and the CAR areas under the curve to ground (AUCg) were associated with their childhood trauma questionnaire (CTQ) physical neglect scores and CTQ total scores. In addition, the CTE/MDD group also showed a highest post-DST cortisol concentration and a decreased glucocorticoid feedback inhibition among four groups of subjects. The present findings suggested that childhood trauma was associated with hyperactivity of HPA axis as measured with CAR, potentially reflecting the vulnerability for developing depression after early life stress exposures. Moreover, dysfunction of the GR-mediated negative feedback control might contribute to the development of depression after CTE.     

Use of saliva cortisol in the dexamethasone suppression test

In a sample of 26 inpatients (15 primary endogenous depressives and a heterogeneous comparison group of 11 psychiatric patients), results of the dexamethasone suppression test (DST) for endogenous depression were compared when cortisol was measured in plasma (total and free) and in saliva. Results showed a close linear relationship among plasma total and free cortisol, plasma total cortisol, and saliva cortisol, and between free plasma and saliva cortisol. A saliva cortisol cutoff point of 70 ng/dl achieved the same sensitivity (67%), specificity (91%), and diagnostic confidence (91%) as the best cutoff scores of plasma total cortisol (5 μ/dl) and plasma free cortisol (0.15 μ/dl). These results suggest that saliva cortisol, which directly reflects the biologically active fraction of cortisol, can be used as a reliable and more practical index in the DST, especially in outpatients.     

Discrimination between patients with melancholic depression and healthy controls: comparison between 24-h cortisol profiles, the DST and the Dex/CRH test

Diurnal (24-h) cortisol profiles were compared to DST and Dex/CRH test outcomes with regard to their discriminative power in depressive disorder. With regard to several statistical measures (effect sizes, area under the curve) we found 24-h cortisol profiles to better discriminate between healthy controls and inpatients with the melancholic subtype of depression compared to the DST and Dex/CRH test. In search of a shortened time interval we found the 2-h time window 1000-1200 h of the cortisol profile to be the one with the highest sensitivity (83.3%) and specificity (87.9%). The specificity of the DST was 93.3% and somewhat higher than that of the cortisol profiles and the Dex/CRH test (87.9% and 78.8.%, respectively). However, the sensitivity of the DST was very low (30.8%), in fact similar to that of the Dex/CRH test (30.8%), but much lower than that of the 1000-1200 h interval (83.3%). The assessment of cortisol in plasma is an easy to perform, cost-saving method for the evaluation of the HPA system activity, which may have a series of clinical and scientific implications for the depressive disorder.     

Number of cortisol time-points and dexamethasone suppression test sensitivity for major depression

Failure to suppress cortisol secretion after administration of dexamethasone has been reported to be a diagnostic marker for major depression and to have prognostic implications when repeated after antidepressant treatment. The pulsatile pattern of cortisol secretion suggested to us that increasing the number of post-dexamethasone cortisol determinations might significantly increase the sensitivity of the dexamethasone suppression test (DST) for major depression. With a conventional two-point DST (1600 h and midnight), 5% of 20 normal volunteers, 8% of 13 inpatients with non-major depressions, and 31% of 65 inpatients with primary major depression failed to suppress. With six post-dexamethasone points (0800 h, 1200 h, 1600 h, 2000 h, 2200 h, midnight), the respective percentages were 10, 15 and 44%. The additional points increased the sensitivity from 31 to 44%, mostly by identifying more major depressives with a "late escape" pattern. If a clinician is using the DST to establish a marker for major depression that can be repeated to monitor response to treatment and the likelihood of relapse, then perhaps the increased sensitivity of the six-point DST would be helpful, despite a modest decrease in specificity from 94 to 88%.     

Mean 14.00-17.00 h plasma cortisol concentration and its relationship to the 1 mg-dexamethasone suppression response in depressives and controls

Three-hour cortisol-profiles and cortisol responses to a 1 mg dose of dexamethasone were recorded in 31 depressed patients and nine controls. The data indicate that the likelihood of detecting non-suppressible cortisol concentrations after dexamethasone is significantly increased in depressed patients with a hypersecretion of cortisol. However, a considerable subsample of normosecretors shows abnormal DST results. Conversely, hypersecretion is often associated with dexamethasone suppression. In this study a 1 mg-DST did not reflect the adrenocortical activity with ultimate accuracy. Therefore any attempts which correlate psychopathological or biological data with pituitary-adrenal activity and use a DST-result as measure are criticizable . Data derived from volunteers illustrate that medical factors such as weight-loss, steroid-containing contraceptives and sleep deprivation can make a pituitary-adrenal activity test ambiguous.     

Occurrence of high concentrations of postdexamethasone cortisol in elderly psychiatric inpatients

The authors retrospectively studied 161 psychiatric inpatients who had received a dexamethasone suppression test (DST). The majority of the patients were over 60 years old, female, and had concurrent chronic medical illnesses. Age was significantly correlated with log-transformed postdexamethasone cortisol concentrations in the 118 nondemented patients with major depression. Four p.m. cortisol concentrations greater than 15 micrograms/dl occurred in 15 patients. All were over 60 years old; all but one had major depressive disorder (MDD); and five had dementia plus MDD. In the same population, a 5 micrograms/dl criterion did not distinguish MDD from non-MDD patients. The results support the existence of a clinically relevant age effect on the DST in patients with MDD. Elderly depressed patients with markedly elevated cortisol concentrations occur frequently, and warrant further clinical and pathophysiological study.     

Post-dexamethasone cortisol as a predictor for the efficacy of electroconvulsive therapy in depressed inpatients

Background

Although several variables have been studied as a possible predictor for the efficacy of ECT, results regarding hypercortisolism have been inconsistent. This prospective study evaluates the relation between pre-treatment cortisol levels and the efficacy of ECT in a population of drug-free inpatients with severe major depression.

Methods

At the inpatient depression unit, 18 patients meeting the DSM-IV criteria for depressive disorder, and with scores of at least 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D), were treated with bilateral ECT twice weekly. The HAM-D evaluated depression severity and was performed within 3 days prior to ECT, weekly during the course of ECT, and within 3 days after the last treatment. The outcome criterion was defined a priori as the change on the HAM-D score. Salivary cortisol was assessed within 3 days prior to ECT at two time points, followed by 0.5 mg dexamethasone ingestion. The following day, salivary cortisol was again assessed at two time points. The generalized linear model was used to assess the relation between salivary cortisol levels and reduction in HAM-D score as continuous variables.

Results

Higher levels of salivary cortisol at 9 AM after 0.5 mg dexamethasone ingestion are associated with a greater reduction in HAM-D score (B = −0.279, 95% CI: −0.557 to −0.01, s.e. = 0.13, p = 0.049; R square = 0.23; adjusted R square = 0.13).

Conclusion

This study suggests that higher levels of post-dexamethasone salivary cortisol at 9 AM are predictive of ECT efficacy.