Lower Cortisol Awakening Response Research Articles

Aging, Health Behaviors, and the Diurnal Rhythm and Awakening Response of Salivary Cortisol

Background/Study Context: The cortisol diurnal rhythm has previously been examined in relation to age and health behaviors. However, less is known about the relationship between multiple health behaviors and diurnal cortisol in the context of aging, where it is possible that the impact of health behaviors on cortisol varies as a function of age. This study compared the awakening response and diurnal rhythm of cortisol in young versus older adults in relation to health behaviors. Methods: Twenty-four young students (aged 18–22) and 48 community-dwelling older adults (aged 65–88) completed an assessment of health behaviors (exercise, smoking, sleep, diet, alcohol) over the past year. Salivary cortisol was measured over the course of 1 day: immediately upon awakening, 30 min later, and then 3, 6, 9, and 12 h post awakening. Repeated measures/univariate analysis of variance (ANOVA) was used to test main effects of age and health behaviors, and any interaction effects in relation to diurnal cortisol. Results: Older adults displayed significantly reduced cortisol upon awakening, a lower cortisol awakening response, and a flatter diurnal profile represented by a reduced area under the curve and cortisol slope. There was also a significant interaction of age, cortisol, and diet; younger adults with a higher fat and lower fruit and vegetable intake exhibited the flattened diurnal cortisol phenotype of the older adults. Conclusion: These findings suggest that the diurnal rhythm and awakening response of salivary cortisol is significantly reduced in older adults and that variations in the cortisol diurnal rhythm of younger adults are associated with dietary factors. Younger adults with a poor quality of food intake may be vulnerable to a reduction in the amplitude of the cortisol diurnal profile and this may have implications for other aspects of health.

Salivary cortisol profiles in patients remitted from recurrent depression: One-year follow-up of a mindfulness-based cognitive therapy trial

Few studies have examined changes of diurnal cortisol profiles prospectively, in relation to non-pharmacological interventions such as mindfulness-based cognitive therapy (MBCT). Fifty-six patients remitted from recurrent depression (≥3 episodes) were included in an 8-week randomized controlled trial comparing MBCT plus treatment as usual (TAU) with TAU for depression relapse prophylaxis. Saliva samples (0, 15, 30, 45, 60 min post-awakening, 3 PM, 8 PM) were collected on six occasions (pre- and post-intervention, 3-, 6-, 9-, 12-month follow-up). Cortisol awakening response (CAR), average day exposure (AUCday) and diurnal slope were analyzed with mixed effects models (248 profiles, 1–6 per patient). MBCT (n = 28) and TAU groups (n = 28) did not significantly differ with respect to baseline variables. Intra-individual variability exceeded inter-individual variability for the CAR (62.2% vs. 32.5%), AUCday (30.9% vs. 23.6%) and diurnal slope (51.0% vs. 34.2%). No time, group and time by group effect was observed for the CAR and diurnal slope. A significant time effect (p = 0.003) was detected for AUCday, which was explained by seasonal variations (p = 0.012). Later wake-up was associated with lower CAR (−11.7% per 1-hour later awakening, p < 0.001) and lower AUCday (−4.5%, p = 0.014). Longer depression history was associated with dampened CAR (−15.2% per 10-year longer illness, p = 0.003) and lower AUCday (−8.8%, p = 0.011). Unchanged cortisol secretion patterns following participation in MBCT should be interpreted with regard to large unexplained variability, similar relapse rates in both groups and study limitations. Further research is needed to address the scar hypothesis of diminished HPA activity with a longer, chronic course of depression.

Stress and Abdominal Fat: Preliminary Evidence of Moderation by the Cortisol Awakening Response in Hispanic Peripubertal Girls

Stress and the cortisol awakening response (CAR) have been independently linked to increases in abdominal fat depots. This cross-sectional study examined the CAR as a moderator of the association between stress, visceral adipose tissue (VAT), and subcutaneous abdominal adipose tissue (SAT) in a sample (N = 23) of female peripubertal Hispanic girls aged from 8 to 11. The study included: (i) monitored salivary cortisol collection, (ii) VAT and SAT obtained by multislice magnetic resonance imaging, and (iii) a stressful life events checklist with four domain-specific subscales: peer, family, personal, and school. Regression analysis indicated an interaction of school-related life events and CAR on VAT and SAT, with greater numbers of school-related events being related to greater VAT and SAT for girls with high CAR, but no association with VAT or SAT for girls with low CAR. Similar to job stress in adults, school-related stress in children may contribute to central adiposity, especially for girls with high CAR.

Seasonal differences in the diurnal pattern of cortisol secretion in healthy participants and those with self-assessed seasonal affective disorder

This study compared the daily pattern of free salivary cortisol secretion in winter and in summer between two groups; participants with self-assessed seasonal affective disorder (SAD) and age- and sex-matched healthy controls. Fifty-two participants completed the study with an equal number in each group. The diurnal pattern of cortisol secretion was assessed across two consecutive weekdays in summer, and two in winter, with conditions being counterbalanced. On each study day participants collected multiple saliva samples in the domestic setting to capture the cortisol awakening response (CAR) and declining levels across the day. In addition, perceived stress, anxiety, depression, state stress and state arousal were assessed using validated questionnaires. There was no evidence for any seasonal changes in psychological data or cortisol pattern for the healthy control population. In summer, self-assessed SAD and control participants had similar psychological and cortisol profiles. In winter however, SAD participants reported greater depression, stress and anxiety, and lower levels of arousal. Furthermore, the CAR was significantly attenuated in SAD participants during winter months. There was no difference in cortisol levels during the rest of the day between controls and SAD participants in winter. In line with the above findings and previous research, there was an inverse relationship between the increase in cortisol following awakening and a measure of seasonality in winter. Furthermore in winter, a general dysphoria construct correlated inversely with the CAR, indicating that participants reporting greater depression, stress and anxiety and lower arousal, exhibited lower CARs. In conclusion, during the shortened photoperiod in winter, the cortisol response to awakening is attenuated in participants with self-assessed SAD in comparison to controls. These findings contribute to the understanding of the physiology of SAD.

Dimensions of Depression and Anxiety and the Hypothalamo-Pituitary-Adrenal Axis

Results on the association between depression and the hypothalamo-pituitary-adrenal (HPA) axis have been inconsistent, possibly due to heterogeneity of the DSM-IV category of depression. Specific symptom-dimensions could be used as a more homogenous phenotype in HPA-axis research. Subjects (n = 1029) with a lifetime depression and/or anxiety disorder from the NESDA study (Netherlands Study of Depression and Anxiety) (mean age: 43.0 ± 12.7 years, 67.4% women) provided seven saliva samples to yield the cortisol awakening response (CAR), evening cortisol, and dexamethasone suppression data. The dimensions of the tripartite model (General Distress, Anhedonic Depression, and Anxious Arousal) were measured with the 30-item adapted Mood and Anxiety Symptoms Questionnaire (MASQ-D30) and analyzed in association with the cortisol measures with linear and nonlinear regression. Median (interquartile range) scores of General Distress, Anhedonic Depression, and Anxious Arousal were 20 (14-27), 36 (28-44), and 15 (12-19), respectively, indicating large variability. Nonlinear associations with the shape of an inverted U were found between General Distress, Anhedonic Depression, and Anxious Arousal on one hand and total morning secretion and the dynamic of the CAR by contrast. Both high and low severity levels were associated with a lower CAR, compared with intermediate levels of severity. Most of the associations remained significant when adjusted for covariates and the presence of DSM-IV diagnoses. Nonlinear associations were found between the CAR and the dimensions of the tripartite model. This could explain previous inconsistent findings regarding HPA-axis activity in depressed patients and illustrates the added value of symptom-dimensions for HPA-axis research.

Identifying patterns in cortisol secretion in an older population. Findings from the Whitehall II study

Alterations in the patterning of diurnal cortisol secretion are associated with poor health in clinical populations with 'flat' patterns a particular risk. Flatter patterns in cortisol secretion may reflect impaired negative feedback in the hypothalamic-pituitary-adrenal axis. The correlates of discrete clusters of patterns in the diurnal secretion of cortisol have not been well described in large community dwelling populations. We describe discrete clusters of patterns of cortisol secretion and examine the correlates of these patterns using a latent variable mixture modelling approach. Analyses use data from 2802 participants with complete information on cortisol secretion, age, walking/gait speed, stress, waking up time and sleep duration. Cortisol was assessed from six saliva samples collected at waking, waking plus 30 min, 2.5h, 8h, 12h and bedtime. We find two patterns ("curves") of diurnal cortisol secretion. These curves are described as 'normative' [prevalence 73%] and a 'raised' [27%] curve differentiated by a lower cortisol awakening response in the normative group, a higher diurnal cortisol and 'flatter' pattern of release in the raised group. Older age, being male, a smoker, stress on the day of sampling, slower walking speed and shorter sleep duration increased the odds of being in the raised curve, relative to the normative curve. In conclusion, two patterns of cortisol secretion occur in middle aged men and women. Raised pattern of secretion, which occurs in 27% of our participants is associated with demographic variables, adverse health behaviours, psychosocial environment and impaired physical functioning.

Cortisol awakening response (CAR)’s flexibility leads to larger and more consistent associations with psychological factors than CAR magnitude

The cortisol awakening response (CAR) is increasingly recognized as a potential biological marker of psychological and physical health status. Yet, the CAR literature is replete with contradictory results: both supposedly protective and vulnerability psychosocial factors have been associated with both increased and decreased CAR. In this study, we tested the hypothesis that the CAR flexibility would be a better indicator of psychological status than CAR magnitude. Forty-two men measures of happiness, perceived stress and neuroticism, and took saliva samples immediately on awakening, then at 15, 30, 45 and 60min post-awakening on three study days (i.e., Sunday, Monday and Tuesday). When considering the CAR magnitude, our effects perfectly reflect the inconsistencies previously observed in the literature (i.e., the main effects of the psychological predictors are not consistent with each other, and the effect of one predictor on a given day contradicts the effect of the same predictor on another day). However, considering the CAR flexibility leads to a fully consistent pattern: protective factors (i.e., high happiness, low stress, low neurotiscim) are associated with a flexible CAR (i.e., lower CAR during weekends compared to workdays) whereas vulnerability factors (i.e., low happiness, high stress, high neurotiscim) are associated with a stiff CAR (i.e., same magnitude during weekends and workdays). We conclude that considering the CAR flexibility (e.g., between weekends and workdays) rather than the traditional CAR magnitude might be a way to understand the apparent conflicts in the CAR literature.

Competitive anxiety and cortisol awakening response in the week leading up to a competition

Objectives This study investigated the psychological as well as neuroendocrine stress response across one week before an important sport competition, introducing the cortisol awakening response (CAR) to sport psychological research. Methods On three days in the week before the German Nationals, martial artists ( N = 17) reported their competitive state anxiety and collected five samples of salivary cortisol during the first hour after awakening. Results Hierarchic-linear models and multiple regressions were conducted. Despite a significant rise in “somatic anxiety” ( p < .05), the increment of CAR across the week remained non-significant. A moderator function of competitive anxiety on the released amount of cortisol in the morning was not found significant. Results did not show any significant regression of changes in the neuroendocrine response on changes in state anxiety. Conclusion Non-significant increments of CAR with a closer proximity to the competition may be interpreted as a possible habituation of basal hypothalamus-pituitary-adrenal activity. Moreover, athletes appear to have a lower CAR than found in norm studies, which points to further investigation of interindividual and situational effects on the temporal pattern of the neuroendocrine response to sport competitions.

High cortisol awakening response is associated with an impairment of the effect of bright light therapy

We investigated the predictive validity of the cortisol awakening response (CAR) in patients with non-seasonal major depression. Patients were treated with sertraline in combination with bright or dim light therapy for a 5-week period. Saliva cortisol levels were measured in 63 patients, as an awakening profile, before medication and light therapy started. The CAR was calculated by using three time-points: awakening and 20 and 60 min after awakening. Patients with low CAR had a very substantial effect of bright light therapy compared with dim light therapy, whereas patients with a high CAR had no effect of bright light therapy compared with dim light therapy. High CAR was associated with an impairment of the effect of bright light therapy. This result raises the question of whether bright light acts through a mechanism different from that of antidepressants.

Associations between two job stress models and measures of salivary cortisol

To investigate the association between two job stress models-the job demand-control model and the effort-reward imbalance model-and repeated measures of salivary cortisol among male and female call-centre operators. Daily cortisol profiles consisting of seven time points were measured across two workdays and one leisure day to determine the cortisol awakening response and the cortisol output in the day in 104 volunteers. The employees completed two self-administered questionnaire--the Karasek's demand-control questionnaire and the Siegrist's effort-reward imbalance questionnaire-to assess psychosocial hazards at work. The relations between the perceived workload measures and salivary cortisol levels were analyzed by means of generalized estimating equations method after adjusting for potential confounders (gender, age, educational level, marital status, morning awakening time, sleep duration and quality, weekdays, work schedule, adherence to sampling procedure). The total cortisol amount excreted in the awakening period was positively associated with the job strain measures (high strain vs. low strain: 1.4 (2.4-0.3) nmol/l). In contrast, individuals scoring higher in effort-reward imbalance at work had both lower cortisol awakening response (high imbalance vs. low imbalance: -0.7 (-1.3 to -0.2) nmol/l) and lower diurnal secretory activity (-9.2 (-17.7 to -0.7) nmol/l). Gender, weekday and adherence to sampling schedule significantly influenced the cortisol excretion in the morning period. Our results indicate that the two work stress models differentially affect salivary cortisol output. This finding suggests that combining the information from two complementary job stress models results in improved knowledge on the psychobiological correlates of the psychosocial work environment.

IC-P1-035: Lower cortisol awakening response is associated with smaller hippocampal volumes

Background: Although it has frequently been hypothesized that high levels of glucorticoids have deleterious effects on the hippocampus and may contribute to increased risk for Alzheimer’s disease, this study is among the first to investigate the effect of changes in HPA axis activity on hippocampal volume by assessing the diurnal cortisol profile. Methods: Within the SMART-MR study, a prospective cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 278 patients (mean age 62 9 years) with available data on cortisol and hippocampal volume. Circadian cortisol rhythm was assessed with 6 saliva samples, collected at awakening and 30, 45 and 60 minutes thereafter, and at 10 PM and 11 PM. A low dose of dexamethasone (0.5 mg) was administered at 11 PM and saliva was sampled the next morning at awakening. The diurnal cortisol profile was defined as the cortisol awakening response (CAR), a distinct and dynamic part of the cortisol circadian rhythm (mean cortisol secreted within the first hour after awakening); resting evening values (mean of the two evening measurements); and the suppressibility of the HPA axis (cortisol after 0.5 mg dexamethasone). Volumetric measurements of the hippocampus was performed on a 3-dimensional TFE T1-weighted MRI scan with isotropic voxels. The left and right hippocampus were manually traced and corrected for head size by dividing hippocampal volume by intracranial volume, which was obtained by automatic brain segmentation. Results: Mean total hippocampal volume relative to intracranial volume was 6.2 0.7 ml. Linear regression analyses, adjusted for age and sex, showed that subjects with a lower CAR had smaller hippocampal volumes ( per nmol*h/l increase 0.014 ml; 95% CI 0.001 to 0.028). Evening levels and cortisol levels after dexamethasone were not significantly associated with hippocampal volume. Conclusions: In this population, a lower cortisol awakening response was associated with smaller hippocampal volumes, but evening cortisol levels and cortisol levels after dexamethasone suppression were not. Future studies should determine to what extent lower cortisol secretion after awaking associated with smaller hippocampal volumes increases risk for Alzheimer’s disease.

P4-032: Lower cortisol awakening response is associated with smaller hippocampal volumes

P4-032: Lower cortisol awakening response is associated with smaller hippocampal volumes

Cortisol as predictor in major depression

Background:Mild hypercortisolemia is a biological marker found in a subset of patients with major depression. The cause is supposed to be a malfunction in the corticosteroid receptor. Long standing cortisol excess is toxic to nerve cells and especially the hippocampus seem vulnerable to hypercortisolemia. The well known memory and concentration difficulties found in stress and depressive illnesses are supposed to be partly caused by deterioration of the function of the hippocampus.Methods:The cortisol awakening response(CAR)were measured in saliva by repeated saliva specimens (awakening, 20 min and 60 minutes after awakening) in patient participating in a double blind study using a fixed dosage of sertraline and randomised to either dim or bright light treatment. Cortisol measurements were made before medication and light treatment started. The hypothesis, stated in the protocol, was that saliva cortisol would have a predictive validity of the short term depression outcome.Results:A statistically significant increase in cortisol levels were found during the first hour after awakening. The area under the curve (AUC) from the CAR results was calculated and was found to have a statistically significant predictive validity for depression scores and remission at endpoint. Thus a statistically significant higher proportion of patient with low CAR values were in remission compared to patient with high CAR values. This effect was predominantly seen in the bright light treated group.Conclusion:Patients with a high CAR were less likely to attain remission at endpoint. The high CAR seemed to block the effect of light treatment.

Evidence for altered hypothalamus–pituitary–adrenal axis functioning in systemic hypertension: Blunted cortisol response to awakening and lower negative feedback sensitivity

Hypothalamus-pituitary-adrenal (HPA) axis functioning in systemic hypertension is not fully understood. We explored HPA axis activity and feedback sensitivity to oral administration of dexamethasone in systemic hypertension via assessment of the cortisol awakening response (CAR) and the circadian cortisol profile. The CAR and circadian cortisol profile were assessed in 20 unmedicated and otherwise healthy middle-aged hypertensive men and in 22 normotensive male controls. Salivary free cortisol measures for the CAR were obtained immediately after awakening and 15, 30, 45, and 60 min thereafter. Circadian cortisol secretion was sampled at 08:00, 11:00, 15:00, and 20:00 h. Assessment of the CAR was repeated on the next day after administration of 0.5mg dexamethasone at 23:00 h on the previous night. Hypertensives had a significantly lower CAR (p<0.02) and significantly reduced suppression of the CAR after dexamethasone administration (p<0.01) than normotensive controls. There were no significant differences in cortisol levels at awakening and in circadian cortisol profiles between hypertensives and normotensives. We found evidence for altered HPA axis activity in men with systemic hypertension evident with the CAR. Hypertensives showed relative attenuation in the CAR and in the HPA axis feedback sensitivity following dexamethasone suppression. Such alterations in HPA axis regulation might contribute to the atherosclerotic risk in hypertensive individuals.