Diurnal salivary cortisol in pediatric posttraumatic stress disorder.

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of posttraumatic stress disorder (PTSD). Additional information on basal cortisol levels in children exposed to trauma and experiencing PTSD symptoms may contribute to the understanding of the role of this axis in PTSD. METHODS: Fifty-one children (30 boys and 21 girls, mean age 10.7 years) with a history of exposure to trauma and PTSD symptoms were compared with 31 age- and gender-matched healthy control subjects. Salivary cortisol was obtained from participants during home measurements and was collected four times a day (prebreakfast, prelunch, predinner, and prebed) for up to 3 consecutive days. RESULTS: The clinical group demonstrated significantly elevated cortisol levels when compared with the control group. In addition, exploratory analyses revealed that girls with PTSD symptoms had significantly elevated cortisol levels when compared with boys with PTSD symptoms. CONCLUSIONS: The physiologic response of children with history of trauma and with PTSD symptoms may be characterized by heightened adrenal activity.     

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.     

Early morning cortisol response and emotional processing in adults exposed to postnatal depression in infancy

Emotional processing and cortisol were investigated in non-depressed young adults whose mothers experienced PND. PND-exposed participants (n = 11) had higher waking salivary cortisol and slower performance on an emotional categorization task than controls (n = 15). This supports the hypothesis that early exposure to maternal depression is associated with characteristics reminiscent of vulnerability to depression.     

Longitudinal course of salivary cortisol in post-traumatic stress disorder

OBJECTIVE: In chronic post-traumatic stress disorder (PTSD) lowered cortisol secretion and hypersuppression to dexamethasone has been described repeatedly. However, so far no longitudinal data on the natural course or on the effect of therapy are available. METHOD: We measured basal and post-dexamethasone morning salivary cortisol in a drug-free patient with chronic PTSD (DSM-IV) monthly for nearly 2 years and assessed PTSD and depressive symptoms. RESULTS: Salivary cortisol decreased dramatically 3 months after the traumatic event and in the further course showed an inverse relation to fluctuating but gradually improving PTSD symptoms. Post-dexa-methasone cortisol was suppressed below the detection limit early after trauma and rose again more than 1 year post-trauma. CONCLUSION: Both the potential renormalization of low cortisol levels in improving chronic PTSD and the putative vulnerability to develop PTSD in subjects with increased dexamethasone suppression need further research.     

Further support for higher salivary cortisol levels in "morning" compared to "evening" persons

We analyzed free cortisol daytime levels in a "3-days-7-samples-a-day" protocol in relation to morningness in 112 middle-aged male and female adults derived from the first year of data of the Trier Teacher Stress Study using a one-item proxy for the assessment of chronotype. First, log-transformed cortisol levels were analyzed by a repeated-measures approach controlling for relevant covariates. Results yielded an almost significant main effect of morningness (P=.06). Subsequent within-day analyses, additionally controlling for awakening time, resulted in (marginally) significant main effects of morningness at Day 1 (P=.06) and Day 3 (P=.05) and a significant interaction of sample-by-morningness at Day 2 (P=.04). In sum, the present data seem to corroborate the idea of higher daytime cortisol levels in morning relative to evening types in a sample of healthy middle-aged male and female adults.     

The cortisol awakening response is blunted in psychotherapy inpatients suffering from depression

Determining the salivary awakening cortisol response (ACR) is a non-invasive, reliable method to detect changes in the hypothalamus-hypopituitary-adrenal (HPA) axis. Although a role of the HPA axis in depression is widely recognized, data on the ACR in depressive patients are still scarce and inconsistent. The present study assessed the ACR in depressed patients admitted for inpatient psychotherapy and a comparison group of other psychiatric diagnoses under the same conditions. The ACR was found to be attenuated in depressed as compared to non-depressed patients. This finding is in contrast to previous studies in healthy subjects or depressed outpatients and suggests a blunted rather than an exacerbated HPA reactivity. Further studies will be needed to disentangle the complex relationship between depression and the ACR.     

The influence of childhood abuse on cortisol levels and the cortisol awakening response in depressed and nondepressed older adults

Objectives: Childhood abuse has been associated with depression in later life. This may be related to hypothalamic-pituitary-adrenal (HPA) axis functioning. Therefore we aimed to examine the impact of childhood abuse and its interaction with depression on cortisol levels in older adults.

Methods: Data from 418 participants (mean age 70.8 years) in the Netherlands Study of Depression in Older Persons (NESDO) were used; 187 participants experienced childhood abuse; 309 participants had a diagnosis of depression. Diurnal cortisol levels were determined using six saliva samples from every participant. Multiple regression analyses were performed.

Results: Significant negative associations between childhood abuse and morning cortisol levels were found. In nondepressed persons, both psychological and sexual abuse were associated with greater dynamics of the HPA axis in response to awakening.

Conclusions: Childhood abuse is associated with lower basal cortisol levels at awakening irrespective of major depressive disorder (MDD). Higher reactivity of the HPA axis during the hour after awakening was found in nondepressed participants only, which might suggest that late-life depression modifies the effect of childhood abuse on the HPA axis. Older adults with a history of childhood abuse may be more negatively affected by stress or stressful events and this is reflected in dysregulation of the HPA axis.     

A meta-analysis of blood and salivary cortisol levels in first-episode psychosis and high-risk individuals

Dysregulated cortisol responses and glucose metabolism have been reported in psychosis. We performed a random-effects meta-analysis of cortisol responses in first-episode psychosis (FEP) and psychosis risk states, taking into consideration glucose metabolism. A total of 47 studies were included. Unstimulated blood cortisol levels were significantly higher (g = 0.48, 95 %CI: 0.25–0.70, p < 0.001) in FEP, but not in psychosis risk states (g = 0.39, 95 %CI: −0.42–1.21, p = 0.342), compared to controls. Cortisol awakening response (CAR) was attenuated in FEP (g = −0.40, 95 %CI: −0.68 - −0.12, p = 0.006), but not in psychosis risk states (p = 0.433). Glucose and insulin levels were positively correlated with unstimulated blood cortisol levels in FEP. Our meta-analysis supports previous findings of elevated blood cortisol levels and attenuated CAR in FEP. Future research should focus on identifying the common denominators for alterations in stress hormones and glucose metabolism.     

The low-dose dexamethasone suppression test in fibromyalgia

OBJECTIVE: Fibromyalgia syndrome (FMS) has been associated with decreased cortisol secretion. Patients with posttraumatic stress disorder (PTSD) exhibit similar hypocortisolism in the context of increased negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis. Because trauma and PTSD have been associated with fibromyalgia, we evaluated whether patients with fibromyalgia demonstrate increased HPA feedback sensitivity. METHOD: Baseline blood samples were obtained at 0800 h, and 0.5 mg of dexamethasone was administered to 15 female patients with FMS and 20 normal controls at 2300 h. Adrenocorticotropin (ACTH), cortisol, and dexamethasone levels were measured at 0800 h after dexamethasone intake. RESULTS: There were no group differences in mean ACTH or cortisol levels or in ACTH/cortisol ratio at baseline. After dexamethasone intake, patients with FMS exhibited more pronounced suppression of cortisol but not of ACTH, as well as increased ACTH/cortisol ratios compared with controls. Percent cortisol suppression was associated with pain and fatigue, while ACTH/cortisol ratio and dexamethasone availability were associated with stress and anxiety measures. CONCLUSION: Our results suggest increased sensitivity to glucocorticoid feedback, manifested at the adrenal level, in FMS.     

Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome

OBJECTIVE: The aim of this study was to obtain comprehensive information on basal hypothalamic-pituitary-adrenal (HPA) axis activity in chronic fatigue syndrome (CFS) patients who were not affected by medication or comorbid psychiatric disorder likely to influence the HPA axis. METHOD: Steroid analysis of urine collections from 0600 to 2100 h at 3-h intervals in CFS patients and in controls. RESULTS: Urinary free cortisol and cortisone concentrations showed a significant normal diurnal rhythm, but levels were lower across the cycle in CFS. In contrast, while urinary cortisol metabolites also showed a normal diurnal rhythm, levels were not significantly different between the CFS and controls at any time. Derived metabolite ratios were similar in both groups. CONCLUSION: This study provides further evidence for reduced basal HPA axis function in patients with CFS, based on lower free cortisol and cortisone levels, but this is not corroborated by cortisol metabolite data. The difference between these measures cannot be explained by an altered timing of the diurnal rhythm.     

The association between perceived emotional support,maternal mood,salivary cortisol,salivary cortisone,and the ratio between the two compounds in response to acute stress in second trimester pregnant women

Objective

Little is known about the effect of social support on the reactivity of the hypothalamic–pituitary–adrenal (HPA) axis during pregnancy. Moreover, when investigating the HPA axis most studies do not consider the activity of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), an enzyme within the salivary glands that inactivates cortisol to cortisone. This study explores the association between perceived emotional support and the maternal psychobiological stress response to a standardized naturalistic stressor by assessing maternal mood and the reactivity of salivary cortisol (SalF), salivary cortisone (SalE), and the SalE/(E + F) ratio as a marker of 11β-HSD2 activity.

Methods

Repeated saliva samples and measures of maternal mood were obtained from 34 healthy second trimester pregnant women undergoing amniocentesis which served as a psychological stressor. The pregnant women additionally responded to a questionnaire of perceived emotional support and provided sociodemographic (e.g., maternal educational degree) and pregnancy-specific data (e.g., planned versus unplanned pregnancy).

Results

Perceived emotional support neither showed a significant effect on mood nor on the SalF or SalE response to stress. However, a moderately strong positive association was found between perceived emotional support and SalE/(E + F) (r = .49). Additionally, the final regression analysis revealed a significant negative relationship between educational degree, planned/unplanned pregnancy and SalE/(E + F).

Conclusion

Findings suggest a higher metabolization of cortisol to cortisone in pregnant women with higher emotional support. In contrast, higher maternal education and unplanned pregnancy appear to be associated with decreased salivary 11β-HSD2 activity. The current study emphasizes the importance of taking the activity of 11β-HSD2 into account when examining SalF.     

Higher cortisol awakening response in young adolescents with persistent anxiety problems

OBJECTIVE: The aims of the present study were to test the association between current anxiety problems and basal cortisol levels in a large population sample of young preadolescents, and to test if HPA-axis activity differs between individuals with no, only current, or persistent anxiety problems. METHOD: Cortisol levels of 10- to 12-year olds (n = 1,768) from the general population were measured on three time points during the day. A self-report questionnaire (RCADS) was used to assess current anxiety, a parent-report questionnaire (TPBQ) to assess anxiety problems at age 4. RESULTS: Associations between cortisol levels and current anxiety problems were not found. However, individuals with persistent anxiety problems had higher morning cortisol levels and a higher cortisol awakening response. CONCLUSION: Apparently, only persistent, and not current, anxiety problems are associated with higher HPA-axis activity. Alterations in HPA-axis activity might underlie persistent anxiety problems, or result from the stress accompanied by persistent anxiety problems.     

Basal and dexamethasone suppressed salivary cortisol concentrations in a community sample of patients with posttraumatic stress disorder

Background

Posttraumatic stress disorder (PTSD) has been associated with lower concentrations of cortisol and enhanced suppression of cortisol by dexamethasone, although discrepancies exist among reports. The objective of the study was to determine the pattern of cortisol responses in patients seeking treatment for PTSD resulting from a variety of traumatic experiences and to test whether cortisol responses are significantly related to childhood trauma, severity of symptoms, or length of time since trauma.

Methods

Salivary cortisol was measured at 8 am, 4 pm, and 10 pm on 2 consecutive days before and after a 10 pm dose of .5 mg dexamethasone in 17 psychotropic medication and substance-free subjects with PTSD and 17 matched control subjects.

Results

Repeated-measures analysis of variance (ANOVA) of the baseline salivary cortisol concentrations demonstrated a significant effect for group with higher concentrations in the PTSD group but no significant differences in responses to dexamethasone. The presence of childhood abuse did not significantly affect salivary cortisol concentrations, and there was no correlation between predexamethasone cortisol and either the severity of PTSD symptoms or the time since the index trauma.

Conclusions

Neither low basal concentrations nor enhanced suppression of cortisol are consistent markers of a PTSD diagnosis.