Cortisol Awakening Response Magnitude Research Articles

Anticipated stress predicts the cortisol awakening response: An intensive longitudinal pilot study

The cortisol awakening response (CAR) has been hypothesized to prepare the body for anticipated demands of the upcoming day. This pilot study investigates the influence of anticipated stress on the upcoming day on the CAR, using an intensive longitudinal design with ecological momentary assessments. Over a 30-day period, three healthy participants collected saliva samples each morning at three time points after awakening to measure cortisol levels and completed a questionnaire each evening on the anticipated stress for the following day. Additionally, they wore a smart headband to objectively determine the time point of awakening. There was high variability in the CAR magnitude within participants over time. A multi-level model was estimated to investigate the influence of anticipated stress on the CAR. Results indicated that anticipated stress is predictive of the CAR on the following morning, with higher anticipated stress being associated with increased cortisol levels at the post-awakening time points. These findings underscore the role of stress anticipation in modulating the CAR and highlight the importance of considering within-person variation and temporally lagged effects in biopsychological research.

017 The Circadian Variation of the Cortisol Awakening Response

Abstract Introduction The Cortisol Awakening Response (CAR) is a rapid increase in cortisol levels at awakening that lasts for about 1 hour. This secretory phenomenon has been proposed to be independent of circadian cortisol regulation. However, the contribution of the circadian system to the CAR remains unclear. The aim of this study is to assess the circadian variation of the CAR. Methods A total of eleven healthy participants (1 woman; 22.6 ± 3.4 years old) were enrolled. Following an 8-h baseline sleep period aligned to their habitual sleep times, participants underwent a 72-h ultradian sleep-wake cycle procedure (USW) consisting of 60-min wake periods in dim light (<10 lux) alternating with 60-min nap opportunities in total darkness. Participants remained in a semi-recumbent posture during the procedure. Salivary cortisol samples were collected at 0, 15, 30, and 50 minutes after waking up from each nap. Linear mixed-effects regression analyses were performed on log-transformed cortisol data from wake periods corresponding to the habitual bedtime (biological night) and habitual wake-time (biological morning). These served as proxies of circadian phases characterised by lowest and maximal cortisol secretory activity, respectively. Total cortisol secretion and CAR magnitude during these periods were computed, respectively, as the Area Under the Curve with respect to ground (AUCg) and to increase (AUCi) and compared with paired-samples t-tests. Results Significant main effects of wake period (p<.001) and sample time (p=.023) were found, with no interaction (p=.167). Cortisol levels were higher in the biological morning compared to the biological night and increased with elapsed time awake. The total amount of cortisol secreted (AUCg) after waking in the biological morning was significantly greater than during the biological night (p<.001). No significant differences between circadian phases were found in the AUCi (p=.223). Conclusion Our study suggests that some features of the CAR may at least partially be under circadian control. These findings are relevant for the understanding of the physiological mechanisms underlying circadian misalignment in shift workers and patients with severe sleep disorders. Support (if any) Project funded by the Canadian Institutes of Health Research. I.R.B received a Barrie Foundation Fellowship. A.K. received a Fonds de Recherche en Santé du Québec postdoctoral fellowship.

The cortisol awakening response predicts a same-day index of executive function in healthy young adults

The cortisol awakening response (CAR) is associated with various aspects of cognition, including executive function, in older adult and clinical samples. However, the association between these variables in the healthy functioning population is not well understood due to the limited number of appropriately controlled studies. This study explored the association between the CAR and a set shifting index of executive function in 55 (44 females) healthy participants aged 20.2 ± 3.0 years. Notoriously, assessment of the CAR from self-collected saliva samples within the domestic setting is subject to sample timing error, so electronic monitoring of both awakening and sampling times were employed. Participants attended the laboratory in the afternoon of CAR assessment for testing on the Attention Switching Task of the CANTAB neuropsychological testing battery. A positive association was found between CAR magnitude and attention-switching performance in the afternoon of the same day. This was independent of known relevant CAR covariates, but only evident in CAR data collected without delay exceeding 8 min post-awakening. These findings offer insight into a potential role for the CAR in modulating cognitive functions associated with the pre-frontal cortex.

Competition Stress Leads to a Blunting of the Cortisol Awakening Response in Elite Rowers.

Background: Anticipation of forthcoming demands is often met with biological up-regulation, for example, levels of the stress hormone cortisol are typically elevated immediately prior to an anticipated event. Similarly, the cortisol awakening response (CAR), a surge in cortisol in the period following waking, is elevated on days of anticipated demand and this is viewed as an adaptive response in the preparation for challenge. This study assessed the effects of competition as an anticipated challenge in elite rowers.Methods: Elite rowers (N = 8) were assessed during two training and two competition weekends. Each assessment involved the measurement of self-reported competitive (cognitive and somatic) anxiety and salivary diurnal cortisol across 2 days representing a preparation day prior to either a training or competition day. Competitive anxiety was measured each morning and saliva samples were provided immediately upon waking and 30 min post waking (CAR) and before bed.Results: Self-reported cognitive and somatic anxiety levels were significantly greater during the competition phase compared with training. Additionally, levels of cognitive anxiety were greater on the day of competition compared with the preparation day. CAR magnitude was significantly reduced during the competition phase compared with training; however, there were no differences between preparation and event days.Conclusions: Reduced or blunted CARs are typically observed in chronically stressed populations and are characteristic of burnout and fatigue. While an increased CAR during competition may represent an adaptive response to challenge, blunted CARs and the concomitant increases in competitive anxiety observed here indicate maladaptive responding during a period where maximized functioning is critical.

The cortisol awakening response predicts a same-day index of executive function in healthy young adults

The cortisol awakening response (CAR) is associated with various aspects of cognition, including executive function, in older adult and clinical samples. However, the association between these variables in the healthy functioning population is not well understood due to the limited number of appropriately controlled studies. This study explored the association between the CAR and a set shifting index of executive function in 55 (44 females) healthy participants aged 20.2 ± 3.0 years. Notoriously, assessment of the CAR from self-collected saliva samples within the domestic setting is subject to sample timing error, so electronic monitoring of both awakening and sampling times were employed. Participants attended the laboratory in the afternoon of CAR assessment for testing on the Attention Switching Task of the CANTAB neuropsychological testing battery. A positive association was found between CAR magnitude and attention-switching performance in the afternoon of the same day. This was independent of known relevant CAR covariates, but only evident in CAR data collected without delay exceeding 8 min post-awakening. These findings offer insight into a potential role for the CAR in modulating cognitive functions associated with the pre-frontal cortex.

Variability of the cortisol awakening response and morning salivary oxytocin in late adolescence.

Exogenously administered oxytocin interacts with the hypothalamic-pituitary-adrenal (HPA) axis to modulate endogenous cortisol levels, suggesting a synergistic role for these two hormones in the response to stress, cognitive performance and the development of psycho-behavioural disorders. The cortisol awakening response (CAR) is considered a reliable measure of HPA axis function in humans. However, the CAR appears to vary considerably from day to day and may be strongly influenced by the anticipated demands of the day ahead. The level of variation intrinsic to the CAR is unclear because few studies have examined the CAR in the absence of daily environmental variation. It is not known whether oxytocin has a similar or complementary awakening response. Therefore, over three consecutive days, we examined 12 adolescents (aged 15-17years) in a highly-controlled sleep laboratory. Saliva was collected on days 4-6 of a 9-day laboratory visit. Cortisol and oxytocin levels were determined by an enzyme-linked immunosorbent assay from saliva sampled at 0, 15, 30 and 45minutes, and 8 and 12hours post-awakening. CAR magnitude varied between days and was associated with sleep duration and pre-awakening sleep stage. Conversely, oxytocin levels dropped dramatically in the first 15minutes post-awakening and were highly consistent across participants and days. Older participants had higher awakening oxytocin concentrations. Although cortisol increases and oxytocin rapidly declines upon awakening, their diurnal variation does not appear to be related at basal, peripheral levels, consistent with a previous finding that exogenously administered oxytocin only modulates cortisol under conditions of stress.

Assessment of the cortisol awakening response: Real-time analysis and curvilinear effects of sample timing inaccuracy

The cortisol awakening response (CAR) is typically measured in the domestic setting. Moderate sample timing inaccuracy has been shown to result in erroneous CAR estimates and such inaccuracy has been shown partially to explain inconsistency in the CAR literature. The need for more reliable measurement of the CAR has recently been highlighted in expert consensus guidelines where it was pointed out that less than 6% of published studies provided electronic-monitoring of saliva sampling time in the post-awakening period.Analyses of a merged data-set of published studies from our laboratory are presented. To qualify for selection, both time of awakening and collection of the first sample must have been verified by electronic-monitoring and sampling commenced within 15min of awakening. Participants (n=128) were young (median age of 20 years) and healthy. Cortisol values were determined in the 45min post-awakening period on 215 sampling days. On 127days, delay between verified awakening and collection of the first sample was less than 3min (‘no delay’ group); on 45days there was a delay of 4–6min (‘short delay’ group); on 43days the delay was 7–15min (‘moderate delay’ group).Cortisol values for verified sampling times accurately mapped on to the typical post-awakening cortisol growth curve, regardless of whether sampling deviated from desired protocol timings. This provides support for incorporating rather than excluding delayed data (up to 15min) in CAR analyses. For this population the fitted cortisol growth curve equation predicted a mean cortisol awakening level of 6nmols/l (±1 for 95% CI) and a mean CAR rise of 6nmols/l (±2 for 95% CI). We also modelled the relationship between real delay and CAR magnitude, when the CAR is calculated erroneously by incorrectly assuming adherence to protocol time. Findings supported a curvilinear hypothesis in relation to effects of sample delay on the CAR. Short delays of 4–6min between awakening and commencement of saliva sampling resulted in an overestimated CAR. Moderate delays of 7–15min were associated with an underestimated CAR. Findings emphasize the need to employ electronic-monitoring of sampling accuracy when measuring the CAR in the domestic setting.

Detailed time course of the cortisol awakening response in healthy participants

The cortisol awakening response (CAR) can be assessed from saliva samples collected at home, which confers ecological validity but lacks researcher oversight. Participant non-adherence to requested saliva sampling regimes leads to inaccurate CAR estimates. Moderate sampling delays of just 8 (5–15) min between awakening and commencement of saliva sampling are reported to result in over-estimated CAR magnitude and earlier peaking. This has been attributed to an observed ‘latent’ period in which cortisol secretion does not increase for up to 10-min after awakening. Replication of this finding is essential as the findings have considerable implications for CAR research. Healthy participants (n=26) collected saliva samples at 5-min intervals for 60min on 2 consecutive typical weekdays. Full electronic monitoring of awakening and sampling enabled exclusion of non-adherent data (i.e., delays of greater than 5min between awakening and collection of the first sample). In the 0–15min post awakening segment of the CAR a quadratic effect was observed, with no difference between the awakening and 5 and 10min samples. Moderate sampling delays will shift assessment of the CAR just sufficiently along the time axis to not impact upon measurement of the first sample but to remove the immediate post-awakening latent period from CAR estimates—whilst retaining later estimates of elevated cortisol secretion. The implication from these results is that accurate CAR measures can only be determined from data with strict adherence to commencement of saliva sampling following awakening.

Cortisol Awakening Response in Elite Military Men

Accruing evidence implies that the response magnitude and pattern of salivary cortisol after awakening may be reliable biological predictors of morbidity and mortality. Little is known of these variables in elite military members who are chronically exposed to extreme occupational environments. PURPOSE: To establish summary parameters of cortisol awakening response (CAR) magnitude and pattern in elite military men, and to evaluate the stability of each parameter across two days. METHODS: Fifty-eight healthy, male active-duty U.S. Navy SEALs (mean ± SE age 34.0 ± 0.9 years) self-collected salivary hormone samples in a non-deployed, free-living setting. Samples were collected on two consecutive midweek workdays upon waking, +30 min, +60 min, 1600, and 2100. Following established guidelines, summary parameters of both CAR magnitude and pattern were computed. The stability of each parameter was evaluated via correlational analyses and Cronbach’s alpha. RESULTS: Three measures of CAR magnitude (i.e., peak value, area under the curve with respect to ground, and average of morning samples) and three measures of CAR pattern (i.e., area under the curve with respect to increase, reactivity, and slope) were derived. All three measures of CAR magnitude demonstrated high stability across two days (r value range: 0.59 - 0.62, all p < 0.001, Cronbach’s alpha (α) range: 0.74 - 0.77). One measure of CAR pattern (reactivity) exhibited mediocre stability (r(55) = 0.35, p < 0.01, α = 0.52), while the other two were not stable. Mean ± SE reactivity was 59.5 ± 9.4, while 10 subjects (17.5%) were negative-reactors. CONCLUSIONS: Several useful summary parameters of CAR magnitude and pattern were derived in this unique sample of elite military men. However, more robust evidence of stability across days prevailed for magnitude parameters. Subsequent analyses will evaluate predictive validity of each CAR parameter, effects of participant compliance, and comparisons to evening sampling methods.

Day differences in the cortisol awakening response predict day differences in synaptic plasticity in the brain

The cortisol awakening response (CAR) is the most prominent, dynamic and variable part of the circadian pattern of cortisol secretion. Despite this, its precise purpose is unknown. Aberrant patterns of the CAR are associated with impaired physical and mental health and reduced cognitive function, suggesting that it may have a pervasive role or roles. It has been suggested that the CAR primes the brain for the expected demands of the day but the mechanisms underlying this process are unknown. We examined temporal covariation of the CAR and rapid transcranial magnetic stimulation (rTMS)-induced long term depression (LTD)-like responses in the motor cortex. Plasticity was evaluated across 180 measures from five time points on four sessions across nine healthy researcher participants, mean age 25 ± 2.5 years. Plasticity estimates were obtained in the afternoon after measurement of the CAR on 4 days, at least 3 days apart. As both CAR magnitude and rTMS-induced responses are variable across days, we hypothesized that days with larger than individual average CARs would be associated with a greater than individual average plasticity response. This was confirmed by mixed regression modelling where variation in the CAR predicted variation in rTMS-induced responses (df: 1, 148.24; F: 10.41; p = 0.002). As the magnitude of the CAR is regulated by the “master” circadian CLOCK, and synaptic plasticity is known to be modulated by peripheral “slave” CLOCK genes, we suggest that the CAR may be a mediator between the master and peripheral circadian systems to entrain daily levels of synaptic plasticity.

Dissecting the impact of sleep and stress on the cortisol awakening response in young adults

Cortisol rises precipitously upon awakening, in what has been called the cortisol awakening response (CAR). Atypical CARs have been linked to a number of negative health outcomes. Yet, our understanding of the possible mechanisms creating these associations remains unclear. Both stress and sleep can influence CAR, and may potentially explain its links to health. However, these factors also impact each other, and their influence on CAR has rarely been studied simultaneously. In order to differentiate their effects, this study examined the impact of daily life hassles, anticipatory stress, and subjectively reported sleep on CAR among 58 college students. Self-reported stress and sleep, as well as salivary cortisol (collected during the first hour after awakening) were obtained across two consecutive days. Total sleep time predicted CAR magnitude, but daily hassles and anticipatory stress did not after accounting for the effect of sleep. Lower total sleep time was associated with lower awakening cortisol and greater CAR. These results provide further evidence for the impact of sleep insufficiency on CAR, and suggest future efforts to use CAR as a stress biomarker should take the impact of sleep into consideration.

Delays of 5–15min 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.

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.

The impact of time of waking and concurrent subjective stress on the cortisol response to awakening

Both time of awakening and stress are thought to influence the magnitude of the cortisol awakening response (CAR), but the relative importance of these factors is unclear. This study assessed these influences in a combined within- and between-subject design. Data were collected from 32 men and women working as station staff in the London underground railway system in three conditions: early-shift days, day-shift days, and control days. Saliva samples were obtained on waking, 30 and 60 min later, together with measures of concurrent subjective stress, sleep quality the night before, and accumulated stress at the end of the day. Participants woke up more than 3.5h earlier on average on early-shift than day-shift or control days, and cortisol levels on waking were lower in the early-shift condition. The CAR (assessed both with increases from waking to 30 min and with area under the curve measures) was greater on early-shift days. However, respondents were more stressed over the hour after waking and reported more sleep disturbance on early-shift days; when these factors were taken into account, the difference in CAR related to experimental condition was no longer significant. Comparisons were also made between individuals who started their day-shifts in the morning and afternoon. The morning shift group woke an average of 2h earlier than did the afternoon shift group, but did not differ on stress, sleep quality, or CAR. Stress assessed retrospectively at the end of the day was not associated with the CAR. We conclude that early waking, stress early in the day, and sleep disturbance often coincide, but need to be distinguished in order accurately to interpret differences in CAR magnitude.