Nina Smyth

Assessment of the cortisol awakening response: Expert consensus guidelines

The cortisol awakening response (CAR), the marked increase in cortisol secretion over the first 30-45 min after morning awakening, has been related to a wide range of psychosocial, physical and mental health parameters, making it a key variable for psychoneuroendocrinological research. The CAR is typically assessed from self-collection of saliva samples within the domestic setting. While this confers ecological validity, it lacks direct researcher oversight which can be problematic as the validity of CAR measurement critically relies on participants closely following a timed sampling schedule, beginning with the moment of awakening. Researchers assessing the CAR thus need to take important steps to maximize and monitor saliva sampling accuracy as well as consider a range of other relevant methodological factors. To promote best practice of future research in this field, the International Society of Psychoneuroendocrinology initiated an expert panel charged with (i) summarizing relevant evidence and collective experience on methodological factors affecting CAR assessment and (ii) formulating clear consensus guidelines for future research. The present report summarizes the results of this undertaking. Consensus guidelines are presented on central aspects of CAR assessment, including objective control of sampling accuracy/adherence, participant instructions, covariate accounting, sampling protocols, quantification strategies as well as reporting and interpreting of CAR data. Meeting these methodological standards in future research will create more powerful research designs, thus yielding more reliable and reproducible results and helping to further advance understanding in this evolving field of research.

Delays of 5–15 min between awakening and the start of saliva sampling matter in assessment of the cortisol awakening response

Linking psychosocial measures to the cortisol awakening response (CAR) demands accurate saliva sampling times. Monitoring adherence to the saliva sampling protocol requires electronic monitoring of both awakening and sampling times since self-reported times are inaccurate. Delays greater than 15 min between awakening and commencement of saliva sampling reduce CAR magnitude. Less delay has been judged tolerable but remains unexplored for different magnitude measures, and for timing of the CAR peak. Study 1: Fifty healthy females (21 ± 4 years) were instructed to collect saliva on four days at 0, 15, 30 and 45 min post-awakening (samples 1-4). Both self-reported awakening and sampling times were electronically monitored using actigraphy and track caps. Self-reported awakening was later than actigraph estimated awakening (median difference of 4 min). Estimates of CAR magnitude were significantly greater on non-adherent days (delay of 5-15 min) compared to adherent days (delay<5 min). On non-adherent compared to adherent days cortisol on average peaked earlier, at sample 3 rather than at sample 4. Study 2: Accurately timed cortisol values were obtained in an intensive investigation of 10 participants who collected saliva on 2 days every 5 min for 30 min post-awakening. Cortisol did not significantly increase until 10 min post-awakening, suggesting a time lag may be typical between awakening and observation of a cortisol increase. We conclude that moderate delays between awakening and collection of saliva samples previously considered tolerable result in erroneous estimation of CAR magnitude and timing of the peak. These results are attributed to an approximate 10 min time lag between awakening and the start of the cortisol rise. The absence of this latent period in calculations leads to overestimation of the CAR magnitude on moderately non-adherent sampling days. These findings, if more universally generalizable, will further theoretical understanding of the physiology of the CAR, but are methodologically challenging for researchers since self-reported awakening times are not accurate enough to override the concerns raised. However accurate electronic measurement of adherence to protocol would enable sampling delays to be taken into account in computing CAR estimates.

Anxious attachment style predicts an enhanced cortisol response to group psychosocial stress

Abstract Insecure attachment style is associated with poor health outcomes. A proposed pathway implicates the hypothalamic-pituitary-adrenal axis (HPA-axis), dysregulation of which is associated with a wide range of mental and physical ill-health. However, data on stress reactivity in relation to attachment style is contradictory. This relationship was examined using the novel Trier Social Stress Test for groups (TSST-G): a group-based acute psychosocial stressor. Each participant, in the presence of other group members, individually performed public speaking and mental arithmetic tasks. Seventy-eight healthy young females (20.2 ± 3.2 years), in groups of up to six participants completed demographic information and the Vulnerable Attachment Style Questionnaire (VASQ), and were then exposed to the TSST-G. Physiological stress reactivity was assessed using salivary cortisol concentrations, measured on seven occasions at 10-min intervals. Vulnerable attachment predicted greater cortisol reactivity independent of age, smoking status, menstrual phase and body mass index. Supplementary analysis indicated that insecure anxious attachment style (high scores on the insecurity and proximity-seeking sub-scales of the VASQ) showed greater cortisol reactivity than participants with secure attachment style. Avoidant attachment style (high scores for insecurity and low scores for proximity seeking) was not significantly different from the secure attachment style. Attachment style was not associated with the timing of the cortisol peak or post-stress recovery in cortisol concentrations. These findings in healthy young females indicate subtle underlying changes in HPA axis function in relation to attachment style and may be important for future mental health and well-being.

Post awakening salivary cortisol secretion and trait well-being: The importance of sample timing accuracy

Indices of post awakening cortisol secretion (PACS), include the rise in cortisol (cortisol awakening response: CAR) and overall cortisol concentrations (e.g., area under the curve with reference to ground: AUCg) in the first 30-45 min. Both are commonly investigated in relation to psychosocial variables. Although sampling within the domestic setting is ecologically valid, participant non-adherence to the required timing protocol results in erroneous measurement of PACS and this may explain discrepancies in the literature linking these measures to trait well-being (TWB). We have previously shown that delays of little over 5 min (between awakening and the start of sampling) to result in erroneous CAR estimates. In this study, we report for the first time on the negative impact of sample timing inaccuracy (verified by electronic-monitoring) on the efficacy to detect significant relationships between PACS and TWB when measured in the domestic setting. Healthy females (N=49, 20.5±2.8 years) selected for differences in TWB collected saliva samples (S1-4) on 4 days at 0, 15, 30, 45 min post awakening, to determine PACS. Adherence to the sampling protocol was objectively monitored using a combination of electronic estimates of awakening (actigraphy) and sampling times (track caps). Relationships between PACS and TWB were found to depend on sample timing accuracy. Lower TWB was associated with higher post awakening cortisol AUCg in proportion to the mean sample timing accuracy (p<.005). There was no association between TWB and the CAR even taking into account sample timing accuracy. These results highlight the importance of careful electronic monitoring of participant adherence for measurement of PACS in the domestic setting. Mean sample timing inaccuracy, mainly associated with delays of >5 min between awakening and collection of sample 1 (median=8 min delay), negatively impacts on the sensitivity of analysis to detect associations between PACS and TWB.

Physical fitness and prior physical activity are both associated with less cortisol secretion during psychosocial stress

ABSTRACT Background: Evidence linking fitness and decreased psychosocial stress comes from studies of athletes and typically relies upon self-report measures. Furthermore, there is little evidence regarding the impact of physical activity (PA) prior to a stressor. The aims of this study were to determine whether fitness and prior PA influence cortisol concentrations during psychosocial stress. Methods: Seventy-five non-athletic participants took part in a submaximal walk prior to the Trier Social Stress Test for Groups (TSST-G). During the walk, fitness was assessed using heart rate (HR). A further 89 participants took part in the TSST-G without the walk. Stress responsiveness was assessed using salivary cortisol collected at 10-min intervals on seven occasions. Results: Hierarchical multiple regression revealed that average walking HR accounted for 9% of the variance in cortisol secretion (P = .016), where a higher HR was associated with higher cortisol secretion. Between-subjects ANCOVA revealed that the walking group had a significantly lower cortisol secretion than the non-walking group (P = .009). Conclusions: These findings indicate that fitter individuals have reduced cortisol secretion during psychosocial stress. They also indicate that prior PA can reduce cortisol concentrations during psychosocial stress and are suggestive of a role of PA in reducing the impact of stress on health.

Salivary diurnal cortisol profiles in patients suffering from chronic breathlessness receiving supportive and palliative care services: a cross-sectional study

Chronic breathlessness is a common source of psychological and physical stress in patients with advanced or progressive disease, suggesting that hypothalamic-pituitary-adrenal (HPA) axis dysregulation may be prevalent. The aim of this study was to measure the salivary diurnal cortisol profile in patients receiving supportive and palliative care for a range of malignant and non-malignant conditions and to compare the profile of those experiencing moderate-to-severe disability due to breathlessness against that of patients with mild/no breathlessness and that of healthy controls. Saliva samples were collected over two consecutive weekdays at 3, 6, and 12h after awakening in 49 patients with moderate-to-severe breathlessness [Medical Research Council (MRC) dyspnoea grade ≥3], 11 patients with mild/no breathlessness (MRC dyspnoea grade ≤2), and 50 healthy controls. Measures of breathlessness, stress, anxiety, depression, wellbeing and sleep were examined concomitantly. The diurnal cortisol slope (DCS) was calculated for each participant by regressing log-transformed cortisol values against collection time. Mean DCS was compared across groups using ANCOVA. Individual slopes were categorised into one of four categories: consistent declining, consistent flat, consistent ascending and inconsistent. Controlling for age, gender and socioeconomic status, the mean DCS was significantly flatter in patients with moderate-to-severe breathlessness compared to patients with mild/no breathlessness and healthy controls [F (2, 103)=45.64, p<0.001]. Furthermore, there was a higher prevalence of flat and ascending cortisol profiles in patients with moderate-to-severe breathlessness (23.4%) compared to healthy controls (0%). The only variable which correlated significantly with DCS was MRC dyspnoea grade (rs=0.29, p<0.05). These findings suggest that patients with moderate-to-severe breathlessness have evidence of HPA axis dysregulation and that this dysregulation may be related to the functional disability imposed by breathlessness.

Relationship between post-awakening salivary cortisol and melatonin secretion in healthy participants

Abstract We report the relationship between patterns of post-awakening salivary melatonin and cortisol secretion in healthy participants (n = 51; mean age 21.6 ± 5.0 years). Saliva samples were collected within the domestic setting, at 0-, 15-, 30-, and 45-min post-awakening on 2 consecutive typical weekdays. Analyses were undertaken on data with electronically verified sample timing accuracy (<5-min delay between awakening and the start of saliva sampling). Melatonin secretion declined linearly by an average of 29% within the first 45-min post-awakening. In contrast, there was a marked 112% surge in cortisol, characteristic of the cortisol awakening response. No day differences in melatonin or cortisol secretion were observed but melatonin concentrations were lower with later awakening. Despite contrasting post-awakening changes in these hormones, there was a lack of relationship between overall levels or patterns of melatonin and cortisol during this period.

Assessment of the cortisol awakening response: Summary of the ISPNE expert consensus guidelines

The cortisol awakening response (CAR), the marked increase in cortisol secretion over the first 30–45 min after morning awakening, has been related to a wide range of psychosocial, physical and mental health parameters, making it a key variable for psychoneuroendocrinological research. The CAR is typically assessed from self-collection of saliva samples within the domestic setting. While this confers ecological validity, it lacks direct researcher oversight which can be problematic as the validity of CAR measurement critically relies on participants closely following a timed sampling schedule, beginning with the moment of awakening. Researchers assessing the CAR thus need to take important steps to maximize and monitor saliva sampling accuracy as well as consider a range of other relevant methodological factors. To promote best practice of future research in this field, the International Society of Psychoneuroendocrinology initiated an expert panel charged with (i) summarizing relevant evidence and collective experience on methodological factors affecting CAR assessment and (ii) formulating clear consensus guidelines for future research. This presentation will give a summary of the main results of this undertaking. Consensus guidelines are presented on central aspects of CAR assessment, including objective control of sampling accuracy/adherence, participant instructions, covariate accounting, sampling protocols, quantification strategies as well as reporting and interpreting of CAR data. Meeting these methodological standards in future research will create more powerful research designs, thus yielding more reliable and reproducible results and helping to further advance understanding in this evolving field of research.

Hair cortisol concentrations in relation to ill-being and well-being in healthy young and old females

Hair cortisol concentration (HCC) provides a retrospective measure of long-term (i.e. over a period of months) cortisol secretion and has been shown to be elevated in relation to chronic stress conditions. However associations in healthy participants with subjective ill-being are less clear and associations with well-being have not been explored. The current study examined HCC in relation to independent comprehensive measures of ill-being (stress, depression, anxiety) and well-being (subjective happiness, life satisfaction, psychological well-being) in healthy young and old females (mean±SD: 19.5±2.2years and 78.6±6.7years respectively, total N=115). The data supported evidence of increased total cortisol secretion with increased age. No association between ill-being and HCC was found in either the young or older group of participants. A positive association between HCC and well-being was found in the older participant group which was independent of ill-being and potential confounds. These findings do not support associations between HCC and ill-being in healthy young or old females. However the results suggest that HCC is able to distinguish levels of well-being in healthy older females.

Salivary diurnal cortisol profiles in patients with advanced malignant and non-malignant disease: A cross-sectional study

levelmodeling. Saliva sampleswere collected immediately, 15min, 30min, 45min, 3h, 6h, 9h, and 12h, after waking each day for two consecutive days from 82 healthy elders in Hong Kong (equal number ofmen andwomen,mean age=73.09 yrs). Day, saliva sampling time, and the motivation to strengthen social ties (Network Cultivation) were treated as fixed variables). Cortisol awakening response and diurnal declinewere examined in relation toNetwork Cultivation. Results showed that participants scoring higher onNetwork Cultivation exhibited a stronger cortisol awakening response and a faster diurnal decline in comparison to those who scored lower on Network Cultivation. This pattern of findings suggests that elders who are more socially embedded exhibit a diurnal cortisol profile typically seen in younger people. Development of intervention/education programs to promote social embeddedness in the elderly is warranted.