Cognitive performance in patients with burnout, in relation to diurnal salivary cortisol

This study investigated cognitive performance in patients with burnout, in relation to the flexibility of the hypothalamic-pituitary-adrenal (HPA) axis. Clinical cases with work stress-induced burnout (n = 65), and demographically matched, healthy reference subjects (n = 65), were given six neuropsychological tests and a self-rating scale for cognitive problems. Diurnal salivary cortisol was measured among burnout cases and an external reference group (n = 174), including a dexamethasone suppression test (DST) among burnout cases. Compared with referents, the burnout group under-performed in a cognitive speed test (Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol), but not in any other test of sustained attention, episodic memory, or vocabulary. Burnout cases had considerably more subjective cognitive problems, but ratings were unrelated to test performance. Compared with referents, burnout cases had similar morning salivary cortisol levels and similar awakening response, but lower evening cortisol. Among burnout cases, lower diurnal cortisol variability was related to slower performance in several tests. The DST response showed no consistent relationship with any cognitive parameter. Hence, despite considerable subjective cognitive problems, the burnout group showed only a partial, mild deviation in cognitive performance. A flatter diurnal cortisol profile was related to lower cognitive processing speed, but diurnal cortisol pattern and DST response were normal, suggesting a maintained HPA axis flexibility.     

Examining HPA-axis functioning as a mediator of the relationship between depression and cognition across the adult lifespan

Altered HPA-axis functioning is a hypothesized mechanism for worsened cognition in depression. The current study examines the indirect effects of depression on processing speed, executive functioning, and memory as a function of the HPA-axis. 38 individuals with a depression diagnosis and 50 healthy controls (HCs) aged 18–86 underwent neuropsychological testing and at-home diurnal salivary cortisol collection. Depression was assessed via structured clinical interviews and rating scales. Cognitive composite scores were derived from factor analysis. Daytime cortisol exposure was estimated using area under the curve (AUC). Depression was associated with higher cortisol levels and slower processing speed . A significant suppression effect of AUC was present on the relationship between depression and processing speed. Limitations include the cross-sectional design and limited sample heterogeneity. Though poorly modulated HPA-axis is one proposed mechanism of cognitive alterations in depression, our results did not support this conclusion for processing speed. Alternative mechanisms should be considered to inform interventions to target cognitive alterations in depression.     

Cognitive functioning and cortisol profiles in first episode major depression

Major Depressive Disorder (MDD) is often associated with high levels of stress and disturbances in the Hypothalamic Pituitary Adrenal (HPA) system, yielding high levels of cortisol, in addition to cognitive dysfunction. Previous studies have shown a relationship between cortisol profile and cognitive functioning in recurrent MDD in general. More specifically, the association between hypercortisolism and cognitive functioning, such as memory and Executive Functioning (EF), and also more recently cortisol suppression has been explored. However, no studies have investigated these relationships in patients diagnosed with first episode MDD. The aim of the present study was to examine the relationship between cortisol levels before and after the Dexamethasone suppression test (DST) and cognitive function in first episode MDD patients. Twenty‐one patients meeting the DSM‐IV criteria for a first episode of MDD diagnosis were included in the study. The control group was matched for age, gender and education level. Cortisol was measured in saliva collected with Salivette sampling devices. Saliva samples were collected 4 times during a 24 hours period over two consecutive days: at awakening, after 45 minutes, after 7 hours and at 11 pm. Dexamethasone (1.0 mg) was given orally on Day 1 at 11 pm. The neuropsychological test battery consisted of standardized tests measuring executive functioning (EF) and memory functioning. Cortisol levels did not differ significantly between patients and controls on Day 1, except for the last sample before Dexamethasone administration, where the control group showed higher levels. Both groups showed suppression after Dexamethasone. On Day 2 there was a significant difference between groups at the third sample, showing a significantly lower level in the control group, suggesting that the controls have a more effective suppression profile than the patients. There were no significant correlations between cortisol levels before or after Dexamethasone and cognitive measures. The results indicate impairment on HPA‐axis functioning in first episode MDD patients, with less suppression functioning compared to healthy controls, but no relationship between cortisol profile and cognitive functioning in EF or Memory.     

Diurnal cortisol rhythm and cognitive functioning in toddlers: The Generation R Study

Little is known about the relationship between diurnal cortisol secretion patterns and cognitive function early in life. This population-based study examined whether diurnal cortisol rhythms and cognitive functioning in toddlers are related. Within the Generation R Study, parents of 364 infants (median age: 14.2 months) collected saliva samples at five moments during one day. We assessed the diurnal cortisol rhythm by calculating the area under the curve (AUC), the cortisol awakening response (CAR), and the diurnal slope. Verbal cognitive functioning and fine motor development was determined at age 18 months. Nonverbal cognitive functioning was assessed at age 30 months. A more positive CAR was associated with a lower risk of delay in language comprehension (OR per 1-SD CAR: 0.62, 95%CI: 0.40–0.98, p = .04), a lower risk of nonoptimal fine motor development (OR per 1-SD slope: 0.74, 95%CI: 0.57–0.96, p = .03), and a lower risk of delay in nonverbal cognitive development (OR per 1-SD CAR: 0.58, 95%CI: 0.38–0.90, p = .02). Also, children with flatter slopes had a lower risk of delay in nonverbal cognitive development (OR per 1-SD slope: 0.51, 95%CI: 0.34–0.76, p = .001). Higher AUC levels were associated with a higher risk of delay in language production. These results show that variations in diurnal cortisol rhythms are already associated with variations in cognitive functioning at a young age. Infants with a diurnal cortisol pattern indicative of less stress and more cortisol reactivity, that is, lower AUC levels and a more positive CAR, show a lower risk of delay in cognitive functioning as toddlers.     

C-reactive protein polymorphisms are associated with the cortisol awakening response in basal conditions in human subjects

Cortisol affects the acute-phase response, but it is unknown whether C-reactive protein (CRP), an acute-phase reactant, also affects hypothalamus?pituitary?adrenal axis activity. In the present study, associations were explored between CRP haplotypes with plasma CRP concentrations and basal salivary cortisol level. We included 266 physically healthy Caucasian subjects (103 females and 163 males) aged between 18 and 65 years of whom 94 had a psychiatric disorder in a genetic association study. Six tag single-nucleotide polymorphisms capturing the common genetic variation of the CRP gene were genotyped (i.e. rs2808628, rs2808630, rs1205, rs1800947, rs1417938, and rs3091244) to yield common CRP haplotypes. Plasma CRP concentrations, the salivary cortisol awakening response (CAR) (0, 30, 45, and 60?min after awakening), and the diurnal cortisol decline (11:00, 15:00, 19:00, and 23:00 h) were assessed for 2 days. rs2808628, rs1205, rs1417938, and rs3091244 showed expected associations not only with CRP concentrations, but also with salivary cortisol levels during the CAR. Five well-characterized CRP haplotypes were arranged in ascending order according to increasing CRP levels. There was an inverse linear association between CRP haplotypes and cortisol levels during the CAR, but no association with the diurnal cortisol decline. Hence, genetic variants in the CRP gene that are associated with lifetime plasma CRP levels were also associated with salivary cortisol levels after awakening, in basal, non-inflammatory conditions.     

Diurnal patterns of salivary cortisol and DHEA in adolescent anorexia nervosa

Although there is well-documented evidence for hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis function in anorexia nervosa (AN), there has been little research into secretory patterns of salivary cortisol and dehydroepiandrosterone (DHEA) in this condition. The cortisol awakening response (CAR), a prominent and discrete feature of the cortisol cycle, has not been extensively explored in adolescent AN. Saliva samples were collected at awakening, 30?min and 12 h post-awakening on two consecutive weekdays from eight female adolescents with clinically diagnosed AN and 41 healthy control (HC) age-matched females. Adolescent AN patients had greater salivary cortisol and DHEA concentrations than HC girls at all points. Increased hormone secretion was unrelated to body mass index. However, despite hypersecretion of both hormones, the circadian pattern including the CAR paralleled that of the HC group. Findings from this preliminary study confirm dysregulation of HPA axis function in adolescent AN as evidenced by hypersecretion of both cortisol and DHEA, which share the common secretagogue adrenocorticotropic hormone. However, the parallel diurnal profiles for AN and HC participants, including the CAR, may indicate hypersecretion per se rather than differential regulation of the diurnal pattern of these two adrenal steroids in AN.     

Diurnal cycle of salivary cortisol in older adult men and women with subjective complaints of memory deficits and/or depressive symptoms: relation to cognitive functioning

In populations of young and older adults, it has been shown that individuals may be categorized into one of three diurnal subgroups when salivary cortisol levels are assessed over a 2-day period and compared for their consistency across days: a typical subgroup, a flat subgroup, and an inconsistent subgroup. Interestingly, recent studies have reported that the typical subgroup represents the majority of the young and older adult population, a finding that is difficult to reconcile with previous studies showing increased cortisol levels in older adults with depression or cognitive impairments. In order to assess whether a typical diurnal cortisol profile is representative across different subgroups of older adults, we assessed diurnal cortisol cycle representation in a sample of older adults with subjective complaints of depression and/or memory problems. Furthermore, given the robust relationship between cortisol and cognitive function, the present study examined the association between the three diurnal subgroups and cognitive performance. Forty-two older individuals were recruited on the basis of reporting subjective complaints of either memory problems and/or depressive mood. Participants were asked to sample their saliva over a 2-day period and were then asked to undergo a neuropsychological evaluation that taps into short-term memory, declarative memory and language. The results showed that 69% of the sample presented a Flat cycle of salivary cortisol over a 2-day period while 19% presented an inconsistent pattern and 12% presented a typical pattern. Participants in the flat subgroup were significantly impaired on letter verbal fluency. Furthermore, a relationship was found between diurnal cortisol subgroup representation and subjective complaint profile. These findings show that older adults with complaints of memory problems and/or depressive symptoms do not present the typical profile of the diurnal cortisol cycle, and they provide a preliminary view of how diurnal cortisol profile relates to cognitive function during human aging.     

Job satisfaction and cortisol awakening response in teachers scoring high and low on burnout

The burnout syndrome is an important psychosocial risk in the job context, especially in professions with a strong social interaction, as in the case of teaching. High levels of burnout have been related to negative psychological indicators and hormonal alterations. This study compares job satisfaction and the cortisol awakening response (CAR) in teachers scoring high (HB) and low (LB) on burnout. HB teachers showed lower job satisfaction and no significant differences in the CAR when compared with the LB group. The results of the study suggest a general dissatisfaction with work along with a different functioning of the hypothalamo-pituitary-adrenocortical axis in HB teachers. Although non significantly, they showed a lower magnitude of the CAR than LB teachers. When considering the whole sample, emotional exhaustion and depersonalization correlated negatively and personal accomplishment positively with each subscale of the job satisfaction questionnaire whereas cortisol levels or CAR did not correlate significantly with both burnout subscales and job satisfaction. These results should be taken into account when working to prevent burnout in teachers, as the modified parameters could be considered indicators of the onset or development of the syndrome.     

Association of Hypothalamic-Pituitary-Adrenal Axis Function with Neuropsychological Performance in Children with Mild/Moderate Asthma

The present study examines the relationship between hypothalamic-pituitary-adrenal (HPA) axis function and child psychological/neuropsychological function in a group of children with mild to moderate asthma. The goal of the study was to determine whether child neuropsychological functioning and psychological functioning were associated with cortisol production in response to adrenocorticotropic hormone(ACTH) stimulation when assessed as area under the curve. Data for this study were gathered from 63 children who participated in an ancillary study within the Childhood Asthma Management Program (CAMP) during the pre-randomization phase of the CAMP trial. At 2 of the 8 CAMP clinical centers participants completed an ACTH stimulation test after an overnight stay in the General Clinical Research Center. Gender differences on baseline cortisol and change in cortisol 30 minutes after infusion of ACTH were present. Results further indicated significant associations between cortisol production and measures of child neuropsychological function. Stepwise multiple regression analysis revealed that cortisol change could be predicted by measures of gender, working memory, and arousal maintenance, providing support for the hypothesis that cortisol plays a modest role in the neuropsychological function of children with mild and moderate asthma. In contrast, cortisol production was not associated with child reports of psychological functioning. Limitations to the methods employed in this study are discussed.     

Association of hypothalamic-pituitary-adrenal axis function with neuropsychological performance in children with mild/moderate asthma.

The present study examines the relationship between hypothalamic-pituitary-adrenal (HPA) axis function and child psychological/neuropsychological function in a group of children with mild to moderate asthma. The goal of the study was to determine whether child neuropsychological functioning and psychological functioning were associated with cortisol production in response to adrenocorticotropic hormone(ACTH) stimulation when assessed as area under the curve. Data for this study were gathered from 63 children who participated in an ancillary study within the Childhood Asthma Management Program (CAMP) during the pre-randomization phase of the CAMP trial. At 2 of the 8 CAMP clinical centers participants completed an ACTH stimulation test after an overnight stay in the General Clinical Research Center. Gender differences on baseline cortisol and change in cortisol 30 minutes after infusion of ACTH were present. Results further indicated significant associations between cortisol production and measures of child neuropsychological function. Stepwise multiple regression analysis revealed that cortisol change could be predicted by measures of gender, working memory, and arousal maintenance, providing support for the hypothesis that cortisol plays a modest role in the neuropsychological function of children with mild and moderate asthma. In contrast, cortisol production was not associated with child reports of psychological functioning. Limitations to the methods employed in this study are discussed.     

Differences between diurnal patterns of salivary cortisol and dehydroepiandrosterone in healthy female adolescents

The adrenal hormones cortisol and dehydroepiandrosterone (DHEA) share a common secretagogue: adrenocorticotropic hormone; however, secretion of these hormones can be dissociated suggesting subtle individual regulation at the level of the adrenal gland. We examined differences in the diurnal patterns of cortisol and DHEA secretion in healthy adolescent girls, with the aim of informing the possibility of exploiting these differences to aid interpretation of data from clinical populations in which these patterns can become dysregulated. Fifty-six healthy females aged 10-18 years provided saliva samples at 0 and 30 min (morning samples) and 12 h post-awakening on 2 consecutive weekdays. For morning salivary cortisol in relation to morning DHEA concentrations, correlational analysis revealed only a trend (p = 0.054). Similarly, the association between evening cortisol and DHEA was characterised as a trend (p = 0.084). Mean morning DHEA concentrations showed more day-to-day consistency than equivalent cortisol samples (r = 0.829 for DHEA and 0.468 for cortisol; z = 3.487, p < 0.0005). Unlike the cortisol pattern, characterised by a marked awakening response (cortisol awakening response, CAR), a significant rise in DHEA concentration post-awakening was not evident. Finally, there was a strong association between morning and evening concentrations of DHEA, not found for cortisol. The study shows differences in cortisol and DHEA secretion in the post-awakening period and informs work that seeks to examine correlates of dysregulated hypothalamic-pituitary-adrenal axis function. Parallel examination of both hormones enables enhanced interpretation of aberrant patterns of the CAR, i.e. an exploration of whether dysregulation affects both hormones (reflecting overall steroidogenic capacity) or cortisol alone (CAR-specific mechanisms).     

Cognitive deficits in relation to personality type and hypothalamic-pituitary-adrenal (HPA) axis dysfunction in women with stress-related exhaustion

Exhaustion caused by long-term work-related stress may cause cognitive dysfunction. We explored factors that may link chronic stress and cognitive impairment. Personality, psychiatric screening, and behavior were assessed by self-reporting measures in 20 female patients (mean age 39.3 years; range 26-53) with a preliminary diagnosis of stress-related exhaustion and in 16 healthy matched controls. Cognitive performance was investigated with a detailed neuropsychological test battery. Cortisol axis function was assessed by urinary and saliva collections of cortisol, dexamethasone suppression, Synacthen response, and corticotropin-releasing hormone (CRH) tests. Proinflammatory cytokines were measured. Hippocampal volumes were estimated by magnetic resonance imaging. Multivariate and univariate statistical methods were used to explore putative differences between groups and factors linked to cognitive impairment. Cognitive function clearly differed between groups, with decreased attention and visuospatial memory in the patient group, suggesting frontal cortex/medial temporal cortex-network dysfunction. Increased harm avoidance and persistence was present among patients, with lowered self-directedness linked to lower quality of life, increased anxious and depressive tendencies, and experiences of psychosocial stress. Attention was decreased with concomitantly impaired visuospatial memory. The pituitary (adrenocorticotropic hormone, ACTH) response to CRH was decreased in patients, with an increased cortisol/ACTH response to CRH. However, cortisol production rates, diurnal or dexamethasone-suppressed saliva cortisol levels, and the cortisol response to Synacthen were unaltered. Hippocampal volumes did not differ between groups. These findings suggest that cognitive dysfunction in stress-related exhaustion is linked to distinct personality traits, low quality of life, and a decreased ACTH response to CRH.     

Daily and trait rumination: diurnal cortisol patterns in adolescent girls

Rumination is a maladaptive form of emotion regulation associated with psychopathology. Research with adults suggests that rumination covaries with diurnal cortisol rhythms, yet this has not been examined among adolescents. Here, we examine the day-to-day covariation between rumination and cortisol, and explore whether trait rumination is associated with alterations in diurnal cortisol rhythms among adolescent girls. Participants (N?=?122) provided saliva samples 3 times per day over 3 days, along with daily reports of stress and rumination, questionnaires assessing trait rumination related to peer stress, and diagnostic interviews assessing depression and anxiety. Greater rumination than usual during the day was associated with lower cortisol awakening responses the following morning, but this effect was not significant after accounting for wake time and an objective measure of adherence to the saliva sampling protocol. Trait rumination was associated with lower average cortisol levels at waking and flatter diurnal slopes, accounting for wake time, protocol compliance, and other factors. These patterns may help to explain why rumination is related to the development of psychopathology.     

The awakening cortisol response: methodological issues and significance

The awakening cortisol response (ACR) is a discrete and distinctive part of the cortisol circadian cycle. In healthy adults salivary free cortisol concentrations increase by between 50 and 160% in the first 30 min immediately post-awakening (approximate average increase of 9 nmol/l, range 4-15 nmol/l, estimated to be equivalent to about three secretory episodes). However there are no agreed norms for the absolute concentrations of free cortisol in saliva either immediately post-awakening (range of 4.7-18.5 nmol/l) or 30 min post-awakening (range of 8.6-21.9 nmol/l). This review explores reasons for these discrepancies in normative data including confounding factors such as gender, age, awakening time, light and participant adherence. Although the physiological role of the ACR has not been clearly defined evidence is discussed that suggests it is under a distinct regulatory influence, different from the rest of the diurnal cortisol secretory cycle. Despite the difficulties associated with its measurement a range of studies have demonstrated an association between the ACR and psychosocial variables, stress and health. However it remains unclear whether positive affect and good health are consistently associated with larger or smaller awakening responses. It is early days in the search for the role and significance of the ACR. Its putative role in the regulation of physiological function across the day (e.g. the immune system) and its sensitivity to psychosocial variables make it a prime candidate as an intermediary linking mind and health.     

Worse than sticks and stones? Bullying is associated with altered HPA axis functioning and poorer health

Adolescents (N = 107; M = 12.23 years, SD = 1.09 months) participated in a two-part study examining peer victimization, neuroendocrine functioning, and physical health. In phase 1, adolescents completed questionnaires assessing peer victimization and health. They returned for phase 2 which consisted of two sessions. In session 1, adolescents learned to collect salivary cortisol samples; they collected four samples over 2 non-sports school days. In session 2, adolescents completed the Trier Social Stress Test (TSST) in which they prepared and delivered a speech while cortisol was collected. Peer victimization predicted poor health outcomes and a flattened cortisol awakening response (CAR); this CAR was linked with health problems. During the TSST, victims reported more stress and exhibited altered cortisol levels. Higher cortisol immediately after the stressor and lower cortisol 30 min after the stressor were associated with more health problems. This study provides evidence that the relationship between peer victimization and poor physical health may be explained by differences in neuroendocrine functioning.     

Brain activation patterns in major depressive disorder and work stress-related long-term sick leave among Swedish females

Deficits in executive functioning and working memory associated with frontal lobe dysfunction are prominent in depression and work-related long-term sick leave (LTSL). This study used functional magnetic resonance imaging (fMRI) to investigate potential differences in brain activation patterns in these conditions. In addition, the function of the hypothalamic-pituitary-adrenal (HPA) axis was examined and compared between groups. Since there is a clear overrepresentation of women in these diagnostic groups, and to ensure a more homogenous sample population, only women were included. To examine the neural correlates of relevant cognitive processes in patients on sick leave >90 days due to work-related LTSL, recently diagnosed patients with major depression Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV criteria, untreated), and healthy controls (n?=?10, each group), a 2-back working memory task and a visual long-term memory task were administered during fMRI scanning. HPA axis functioning was investigated using a diurnal curve of saliva cortisol and a dexamethasone suppression test. Task performance was comparable among the three groups. Multivariate image analysis revealed that both memory tasks engaged a similar brain network in all three groups, including the prefrontal and parietal cortex. During the 2-back task, LTSL patients had significant frontal hypoactivation compared to controls and patients with depression. Saliva cortisol measurements showed a flattening of the diurnal rythmicity in LTSL patients compared to patients with depression and healthy contols. Taken together, these findings indicate that work stress-related LTSL and major depression are dissociable in terms of frontal activation and diurnal cortisol rhythmicity.     

Intergenerational predictors of diurnal cortisol secretion in early childhood

The present study examined potential intergenerational links that may contribute to atypical patterns of diurnal cortisol secretion in early childhood. Salivary cortisol samples were collected across 1 waking day in 36 pre‐school children whose mothers are participants in an ongoing longitudinal project. Hierarchical Linear Modeling (HLM) identified statistically significant predictors of individual differences in daily cortisol trajectories. Children displayed relatively low post‐awakening values and flatter cortisol trajectories across the day as a function of unsupportive maternal behaviour, second‐hand smoke and maternal histories of social withdrawal in childhood. These results suggest that individual differences in young children's pattern of diurnal cortisol are associated with a variety of current and historical maternal characteristics and behaviours. The identification of intergenerational predictors of children's diurnal neuroendocrine functioning may provide new insights into the transfer of health and developmental risk from parent to child. Copyright © 2007 John Wiley & Sons, Ltd.     

Abnormal diurnal pattern of cortisol secretion in patients after aneurysmal subarachnoid hemorrhage

Substantial evidence suggests that impairment of the hypothalamus?pituitary system can occur following an aneurysmal subarachnoid hemorrhage (aSAH). Given that the diurnal cortisol rhythm is primarily controlled by the hypothalamus?pituitary system, this study examined whether changes in diurnal cortisol rhythm occurred after aSAH. Cortisol concentrations were measured in the saliva samples collected from patients after aSAH and other types of cerebral hemorrhage (non-aSAH) in the post-awakening period and at night (21:00?h), and the cortisol awakening response (CAR) and diurnal cortisol decline were determined. The area under the cortisol curve from immediately after to 45?min after awakening (CARauc) in the aSAH patient group was comparable to that in the non-aSAH or healthy control groups. However, an obvious cortisol peak was not found after the awakening period, and the morning/nighttime cortisol ratio in the aSAH patient group was significantly lower than that in other examined groups due to higher nighttime cortisol concentrations. In aSAH patients, the CARauc and nighttime cortisol concentrations were negatively correlated with the Fisher CT grade. These results indicate that the diurnal cortisol rhythm is not regulated normally after aSAH, and cortisol secretory activity decreases as the volume of subarachnoid bleeding increases. Our findings will be helpful to understand altered hypothalamus?pituitary?adrenal axis function after aSAH.     

Stress regulation and cognitive control: evidence relating cortisol reactivity and neural responses to errors

In this study, we tested the relationship between error-related signals of cognitive control and cortisol reactivity, investigating the hypothesis of common systems for cognitive and emotional self-regulation. Eighty-three participants completed a Stroop task while electroencephalography (EEG) was recorded. Three error-related indices were derived from the EEG: the error-related negativity (ERN), error positivity (Pe), and error-related alpha suppression (ERAS). Pre- and posttask salivary samples were assayed for cortisol, and cortisol change scores were correlated with the EEG variables. Better error–correct differentiation in the ERN predicted less cortisol increase during the task, whereas greater ERAS predicted greater cortisol increase during the task; the Pe was not correlated with cortisol changes. We concluded that an enhanced ERN, part of an adaptive cognitive control system, predicts successful stress regulation. In contrast, an enhanced ERAS response may reflect error-related arousal that is not adaptive. The results support the concept of overlapping systems for cognitive and emotional self-regulation.     

Cortisol deviations in people with burnout before and after psychotherapy: a pilot study.

Burnout is characterized by exhaustion, cynicism, and feelings of reduced competence. These complaints may be reflected in disturbances in the main stress regulatory endocrine system: the hypothalamus pituitary adrenal (HPA) axis. In this study, the HPA-axis hormone cortisol was sampled after awakening and during the day in 22 participants with clinical burnout and in 21 healthy controls. The cortisol level after awakening was shown to be significantly lower in the burnout group as compared with the control group. Cortisol levels during the day did not differ. The same sampling procedure was repeated after 14 sessions of psychotherapeutic intervention. The intervention led to a significant reduction in complaints and to an increase of the initially lowered morning cortisol levels. No consistent correlations, however, between the changes in subjective complaints and the change in cortisol parameters were found.