Area Under The Curve And Other Summary Indicators Of Repeated Waking Cortisol Measurements Pdf
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- Stress response in Swedish ambulance personnel during priority-1 alarms
- Cortisol Awakening Response, Self-Reported Affect and Exam Performance in Female Students
Stress response in Swedish ambulance personnel during priority-1 alarms
Physical fitness has salutary psychological and physical effects in older adults by promoting neuroplasticity and adaptation to stress. In aging, however, the effects of fitness on the hypothalamic-pituitary-adrenal HPA axis are mixed.
At all daytimes, basal cortisol levels were lower in the HF than the LF group, most notably in the evening and midnight samples, with a significant main effect of physical fitness for cortisol levels overall; the area-under-the-curve for total daily cortisol output was significantly smaller in the HF group.
In conclusion, cardiorespiratory fitness in healthy aging men is negatively correlated with daily cortisol output and contributes to buffering the HPA dysregulation that occurs with advancing age, thus possibly playing a beneficial role in contrasting age-related cognitive and physical decline.
This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information file. Competing interests: The authors have declared that no competing interests exist. Aging is a complex, multifactorial process which shows great individual variability. The trajectory of aging could be related to a variety of factors, including individual differences in the hypothalamic-pituitary-adrenal HPA axis activity [ 1 , 2 ].
Cortisol, the end-product of the HPA axis, acts as a key regulator of inflammation and metabolic activity, as well as a primary agent of the neuroendocrine stress response. Across the day, cortisol secretion levels follows a typical circadian rhythm, sharply increasing within 1 hour after waking and steadily declining thereafter, reaching a nadir in the late evening hours [ 3 ]. Major changes in this diurnal pattern have consistently been observed with aging.
Age-related increase of daytime plasma cortisol levels has been documented using multiple blood sampling [ 4 , 5 ]. These findings have been extended by using salivary sampling method as a non-invasive tool for free cortisol assessment, allowing for frequently repeated measures in more naturalistic settings.
In community-dwelling older adults, diurnal cortisol levels and total cortisol output as the area under the curve, AUC have been reported as increasing with advancing age [ 6 ]. Studies using multiple daily assessments over a period of several days have confirmed these findings: in a group of healthy adults of both sexes, age was found to be associated with an increased daily cortisol AUC, an attenuated wake-evening slope, and a greater cortisol awakening response [ 7 ].
Evidence from a sample of men and women also showed that older age and male gender are independently associated with higher cortisol peak, nadir and AUC [ 8 ]. Interestingly, stress-related psychosocial and affective dimensions seem to play a role in moderating age-related changes in HPA activity: in a large sample spanning 50 years of adulthood, the increase in cortisol output across the day was shown to correlate with higher levels of average negative affect [ 9 ]; in older adults, notably those reporting high levels of perceived stress, decline in self-esteem has been shown to predict an elevated diurnal cortisol output [ 10 ]; a 4-year longitudinal study involving community-dwelling aged persons showed that levels and increases of sleep duration buffered the long-term elevation of diurnal cortisol secretion [ 11 ].
Age-related effects on cortisol secretion have mainly been ascribed to the impairment of feedback inhibition of HPA activity due to neuronal loss within specific brain areas, such as prefrontal cortex and hippocampus, which exert an inhibitory action on stress-sensitive neurons in the amygdala and hypothalamus [ 12 — 14 ].
Importantly, the dysregulation of the HPA axis is regarded as a psychobiological mechanism underlying age-related psychophysical decline [ 15 ]. Frequent HPA activation and increased cortisol secretion are proposed as being etiological in the development of several chronic conditions that become manifest in the older population, including cardiovascular disease [ 16 ], cognitive decline [ 17 — 19 ], depression [ 20 , 21 ], and frailty [ 22 , 23 ].
Another important factor in aging is physical fitness. In older individuals, an active lifestyle is associated with a higher quality of life [ 24 ], and has salutary psychological and physical effects [ 25 ].
However, studies that evaluated the effects of aerobic fitness on HPA axis activity in an aging population have produced conflicting results: no significant differences in serum or salivary cortisol concentrations were observed in life-time exercisers compared to sedentary elderly men, despite remarkable between-group differences in maximal oxygen consumption VO 2max but cortisol was only measured once [ 27 , 28 ].
In contrast, habitual physical activity was shown to buffer against the negative effects of stress in older men and women [ 29 ] by opposing the stress-associated increase in the ratio between salivary levels of cortisol and those of dehydroepiandrosterone DHEA , a hormone of the HPA axis acting as an endogenous glucocorticoid antagonist, with wide-ranging positive effects on immunomodulation and well-being [ 30 ] although VO 2max was not assessed in this study [ 29 ].
Results from intervention studies are also inconclusive: a 6-month aerobic exercise program that increased performance and VO 2max in older adults of both sexes led to a reduction of plasma cortisol levels only in women [ 31 ]. Moreover, a 6-week period aerobic training in sedentary aging men, although increasing VO 2max , failed to affect salivary cortisol output [ 32 ].
In both studies, however, only a single morning measure of cortisol was collected. Acute HPA reactivity to stressful challenges has also been reported to be influenced by physical fitness, with high cardiorespiratory fitness being associated with a blunted cortisol response to psychological stress among older women [ 33 ].
Recent studies, however, have failed to replicate such a finding in younger adults [ 34 , 35 ]. In the current study, the issue of the association between physical fitness and HPA axis activity was reinvestigated in a group of healthy elderly men to assess whether cardiorespiratory fitness levels, indexed by estimating VO 2max , are correlated with differences in HPA axis activity under both basal and stimulated conditions.
This was achieved by measuring in saliva samples: i daily pattern of basal cortisol secretion; and ii the cortisol response to a psycho-cognitive challenge. Healthy elderly men were recruited from various senior citizen centers, all located in the area of Urbino Marche Region, Italy. The initiative was advertised by posting circulars. Subjects willing to participate were given thorough explanations describing the design and aims of the study, and the experimental methods and procedures.
Phone numbers were provided for prospective participants who wanted additional information. Among the 62 subjects initially screened, 29 were eligible age range: 57—79 y; M age : The study was approved by the Ethis Committee of the University of Urbino. A schematic flowchart of the research participants is shown in Fig 1. Age-specific percentiles for cardiorespiratory fitness were retrieved from [ 36 ]. The cardiorespiratory fitness assessment was used for group assignment purposes and was performed using the Rockport Walking Test.
Briefly, the participants were required to walk 1, m jogging and running were not permitted as quickly as possible while wearing a heart rate monitor Polar, Kempele, Finland. The time needed to cover the distance was recorded, and the heart rate was measured immediately at the end of the test subject standing.
Walking time and heart rate were computed in an age-specific regression equation allowing for the estimation of VO 2max. Only the HF and LF subjects were selected to complete the study and proceed with the analysis of circadian and stimulated cortisol secretion see below. Selected participants were then asked to choose one activity category that described their usual pattern of exercise, and were classified as physically active when they met the following criteria: engaging in vigorous-intensity exercise at least 3 time per week for at least 20 minutes per session, or engaging in moderate-intensity exercise for 30 minutes at least 5 times per week for the past 3 years.
Participants who did not meet the established guidelines for physical activity [ 41 ] were classified as physically inactive. The procedures were conducted as previously described [ 42 ]. The subjects were instructed not to consume water or food including candies or chewing gum , and to not brush their teeth within 30 min prior to sample collection.
The lower limit of detection for the assay was 0. To investigate the circadian pattern of basal cortisol secretion, 6 salivary samples were collected. The participants were instructed to start collecting samples only if: i they had a normal duration and good quality of sleep the previous night; and ii they woke-up between 6. The other samples were collected at The total daily cortisol output was indexed as the area under the curve with respect to ground AUC , and was calculated with the trapezoid formula described by Pruessner and colleagues [ 44 ].
On the following day, between 2. The subjects were first accommodated in quiet and relaxed conditions and told about the task procedure. The mental challenge had a duration of 5 min, and consisted of a color-word interference Stroop test 3 min , followed by a 2-min mental arithmetic task counting backwards from in 17 steps as quickly as possible, and starting all over again in case of miscalculation.
To increase the level of situational stress, the test was performed in front of an evaluative audience 2 men and 1 woman. It is worth noting that: i a modified Stroop test administered to a mixed population of young and old women has been shown to trigger a small, but significant, increase in salivary cortisol, which was most pronounced in older women [ 45 ]; and ii multiple-task stress protocols, including color-word Stroop and mental arithmetic tests, were able to trigger a significant increase in urinary [ 46 ] and plasma cortisol [ 47 ] in healthy women of different ages.
Salivary samples were collected at 4 time points across the task: 10 min before starting the test baseline, s1 , 5 min after task completion s2 , and then after 30 s3 and 60 min s4. In accordance with previous literature [ 49 — 51 ], the subjects were subdivided into responders R and non-responders NR on the basis of the amplitude of their cortisol response to mental stress.
In the present study, a baseline-to-peak cortisol rise of 1. Such a criterion was recently shown to serve as an easily applicable and relatively accurate proxy to detect cortisol pulses in experimental designs involving the induction of acute stress in laboratory settings [ 52 ].
In accordance with previous reports [ 50 , 53 ], the NR subjects were excluded from further analyses. The Shapiro-Wilk test rejected normality of data distribution for raw cortisol values, and cortisol data were log-transformed. All the HF subjects met the established criteria for being regarded as physically active. The participants belonging to the LF group did not meet such criteria, and were all classified as physically inactive. As shown in Table 1 , t-testing revealed between-group differences for mean age Both parameters, i.
Salivary cortisol concentrations were found to be consistently lower in the HF than the LF subjects at all sampling times Fig 2A.
In addition, AUC values for total cortisol output across the day were significantly lower in the HF group B The area under the curve values with respect to ground AUC for total cortisol output are lower in the HF participants As reported in Table 3 , mean values of the AUC I and the baseline-to-peak cortisol increments were considerably higher in the HF group, with a steeper cortisol decline during recovery from mental stress, although the differences failed to reach the threshold for significance.
The slope of cortisol rise and the mean peak time of cortisol response were very similar in the 2 groups Table 3. In summary, the results of the present study show that, in healthy elderly men, an active lifestyle and high cardiorespiratory fitness levels are associated with a lower diurnal cortisol output, with minor effects on the cortisol response to acute mental stress.
Previous evidence supports the view that HPA activity control worsens with aging. Moreover, aging has been associated with increased daily cortisol AUC [ 6 — 8 ], a higher cortisol peak and nadir levels [ 8 ], an attenuated wake-evening slope and more pronounced cortisol awakening response [ 7 ], and an increased cortisol:DHEA ratio [ 6 ].
In the present study population, the total daily cortisol output was significantly lower in the high-fit than the low-fit subjects, after controlling for potential confounders such as age and BMI. This observation points to cardiorespiratory fitness as being a factor that is independently associated with better HPA control and lower basal cortisol levels, thus buffering the gradual HPA dysregulation that normally occurs with aging.
Partly contrasting evidence comes from recent studies showing that lifetime exercisers and sedentary elderly men display similar cortisol concentrations in serum and saliva, despite remarkable between-group differences in VO 2max [ 28 , 32 ]. In addition, it has recently been shown that habitual physical activity, although buffering the increase in the cortisol:DHEA ratio associated with stressful life events, does not affect salivary cortisol diurnal rhythms in older adults [ 29 ].
Differences in the study sample and methodology may explain such discrepancies. Hayes and colleagues [ 28 , 32 ] used only a single sample of plasma or saliva in the morning to assess cortisol levels, thus giving no information on total daily output or diurnal rhythm of cortisol secretion. Meanwhile, in the work by Heaney et al.
In addition, the patterns of physical activity reported by the subjects in the high-activity group showed high inter-individual variance, so that some participants might not have exercised at a sufficient level to had an independent impact on cortisol parameters.
In sedentary, elderly indiviudals, increases in VO 2max promoted by exercise programs are not necessarily associated with parallel modifications of cortisol secretion. After a 6-month aerobic training program, a reduction in serum cortisol levels was described in older women, but not in men [ 31 ].
Furthermore, a 6-week aerobic exercise program that was able to increase VO 2max in elderly men failed to affect salivary cortisol output [ 32 ]. A long-term perspective should thus probably be adopted to explain the negative association between VO 2max and cortisol production observed in the present study.
In this study, all high-fit subjects were physically active, i. As a consequence, habitual physical activity may have relatively early and lasting effects on HPA across the lifespan, exerting long-term influences on cortisol regulation. In turn, long-standing levels of HPA activity and cortisol secretion may play a causal role in regulating VO 2max.
Cortisol is a catabolic hormone that stimulates degradation and inhibits the synthesis of muscle proteins, thus causing sarcopenia [ 55 ]. Chronically elevated levels of cortisol production may thus affect VO 2max due to the gradual loss of metabolically active muscle mass. In support of the latter view, alterations in circadian cortisol secretion have been found to be associate with several physical conditions that become manifest at an older age: higher cortisol levels have been associated with a worse physical performance in healthy older adults [ 56 ], and a positive correlation was found in elderly women between evening cortisol and increasing frailty [ 23 ].
In addition, longitudinal studies have proposed that lower night-time cortisol, together with greater diurnal drop in secretion, are associated with a better physical performance in later life [ 57 , 58 ].
Interestingly, in the present investigation, we found that HF- vs. A growing body of evidence from cross-sectional [ 59 — 62 ] and prospective studies [ 18 , 63 — 65 ] has shown that high levels of cortisol secretion correlate with poor cognitive outcomes in older adults but see Singh-Manoux et al. Negative correlation between cortisol levels and the thickness of prefrontal cortical areas has also been reported [ 12 ], providing neurobiological underpinning for the detrimental effect of excessive cortisol levels on cognitive outcomes.
Cortisol Awakening Response, Self-Reported Affect and Exam Performance in Female Students
Mean salivary cortisol levels of the cortisol awakening response for control subjects, subjects with remitted major depressive disorder MDD , and subjects with current MDD. All results are adjusted for sex, age, education, Northern European ancestry, working, weekday, time of awakening, sleep, month with more daylight, smoking, and physical activity. Error bars indicate SE. To convert cortisol to nanomoles per liter, multiply by Mean salivary cortisol levels of the cortisol awakening response for control subjects, subjects with major depressive disorder MDD without comorbid anxiety, and subjects with MDD with comorbid anxiety.
Cumulative cortisol burden is known to influence neuropsychiatric and metabolic disorders. To better understand the relationship between daily cortisol exposure and measures of the diurnal circadian cortisol rhythm, we examined the cross-sectional association of the cortisol awakening response CAR with wake-up cortisol, bedtime cortisol, diurnal slope, and total cortisol area under the curve AUC. Outcome measures included awakening cortisol, CAR awakening to 30 min post-awakening , early decline 30 min to 2 h post-awakening , late decline 2 h post-awakening to bedtime , and the corresponding AUCs.
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Introduction Ambulance personnel consider themselves as being healthy, but studies show they often suffer from stress-related illnesses. However, research on the causes of these stress-related illnesses is limited. This study aimed to examine the stress response of Swedish of ambulance personnel during priority-1 alarms. Methods During 90 priority-1 alarms salivary cortisol concentrations were measured at alarm and after end of alarm, and heart rates measured every 15 seconds. Thirteen men and six women participated in the study. A questionnaire with background data was collected. Non-parametric statistical tests were used.
The aim of the meeting was to explore the conceptual issues relevant to day-time cortisol measurement, and to reach agreement on the day-time cortisol measurement protocol which is best supported by currently available data. While we try to provide an overview of answers to questions about cortisol measurement where there was consensus among meeting participants, we also review areas where consensus was not reached, and note areas where future research is needed. For example, should we be looking at the shape of the daytime rhythm?
Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. DOI: Fekedulegn and M. Andrew and C. Burchfiel and J.
Physical fitness has salutary psychological and physical effects in older adults by promoting neuroplasticity and adaptation to stress. In aging, however, the effects of fitness on the hypothalamic-pituitary-adrenal HPA axis are mixed. At all daytimes, basal cortisol levels were lower in the HF than the LF group, most notably in the evening and midnight samples, with a significant main effect of physical fitness for cortisol levels overall; the area-under-the-curve for total daily cortisol output was significantly smaller in the HF group. In conclusion, cardiorespiratory fitness in healthy aging men is negatively correlated with daily cortisol output and contributes to buffering the HPA dysregulation that occurs with advancing age, thus possibly playing a beneficial role in contrasting age-related cognitive and physical decline. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: To derive the area under the curve and related summary measures of stress from saliva samples collected over time and to provide insight into the interpretation of the derived parameters. In research designed to assess the health consequences of stress these samples are often used as a physiologic indicator of the responsiveness of the hypothalamic-pituitary-adrenal HPA axis. To make these repeated measurements of salivary cortisol more useful in defining the relationships between stress and health there is a need to derive two forms of area under the curve that summarize the measurements: area under the curve with respect to ground AUC G and area under the curve with respect to increase AUC I. The latter parameters, AUC I , however, is seldom used by research scientists. Methods: In this study, interpretation and generic definition of the area under the curve was provided through graphical analyses and examination of its association with other summary measures using data from the Buffalo Cardio-Metabolic Occupational Police Stress BCOPS Pilot Study. In generic form, AUC I is derived as the area under the curve above the baseline value minus the area above the curve below the baseline value.
While we are building a new and improved webshop, please click below to purchase this content via our partner CCC and their Rightfind service. You will need to register with a RightFind account to finalise the purchase. Reviews in the Neurosciences provides a forum for reviews, critical evaluations and theoretical treatment of selective topics in the neurosciences. The journal is meant to provide an authoritative reference work for those interested in the structure and functions of the nervous system at all levels of analysis, including the genetic, molecular, cellular, behavioral, cognitive and clinical neurosciences.