Sequence and seasonal effects of salivary cortisol

Assessments of cortisol levels in saliva have been widely used by both researchers and clinicians as an index of adrenal functioning. Quarterly measurements of morning and evening cortisol levels were determined in a longitudinal study of 147 participants (72 women and 75 men) followed for 1 year each. The analysis of salivary cortisol revealed no significant gender or age differences in the sample. There was a sequence effect in quarterly cortisol values with a progressive decrease in serial measurements, especially notable in the morning values; as well as a seasonal variation in cortisol levels with significantly higher levels found in winter and fall, compared with spring and summer. The findings in this study suggest that repeated saliva sampling and seasonal variation in cortisol levels may independently affect adrenal response and, therefore, need to be accounted for in longitudinal studies.     

Cortisol hypersecretion and the risk of Alzheimer’s disease: A systematic review and meta-analysis

BackgroundMorning cortisol levels have been reported to be elevated among patients with Alzheimer’s disease (AD); yet no meta-analysis has been conducted to confirm the existence and magnitude of this association. It also remains unclear whether hypercortisolism is a risk factor for AD.MethodsPubMed, EMBASE, and PsycINFO were systematically searched for eligible studies. Cross-sectional data were pooled using random-effects meta-analyses; the differences in morning cortisol levels between patients and cognitively normal controls were quantified. Longitudinal studies were qualitatively synthesised due to methodological heterogeneity.Results17,245 participants from 57 cross-sectional studies and 19 prospective cohort studies were included. Compared with cognitively normal controls, AD patients had moderately increased morning cortisol in blood (g = 0.422, P < 0.001; I² = 48.5 %), saliva (g = 0.540, P < 0.001; I² = 13.6 %), and cerebrospinal fluids (g = 0.565, P = 0.003; I² = 75.3 %). A moderate elevation of morning cortisol was also detected in cerebrospinal fluids from patients with mild cognitive impairment (MCI) versus controls (g = 0.309, P = 0.001; I² = 0.0 %). Cohort studies suggested that higher morning cortisol may accelerate cognitive decline in MCI or mild AD patients, but the results in cognitively healthy adults were inconsistent.ConclusionsMorning cortisol was confirmed to be moderately elevated in AD patients and may have diagnostic and prognostic values for AD.     

Psychosocial factors at home and at work and levels of salivary cortisol

BackgroundSalivary cortisol as a physiological measure of stress has attracted great interest in recent years.MethodA 55 women and 28 men, all healthy volunteers, were included in a study on psychosocial factors at work and at home and salivary cortisol. General linear models, univariate and repeated measures, respectively, were used to evaluate the associations between psychosocial factors and cortisol excretion measured six times during a working day. Age, physical activity, tobacco use and the time of the first saliva sample were used as covariates.ResultsIn the women, high degrees of time pressure, effort and effort reward imbalance were significantly associated with higher levels of cortisol. In the men, high degrees of effort, effort reward imbalance and overcommitment were significantly associated with higher levels of cortisol.ConclusionPsychosocial factors are of significance to the level of salivary cortisol. The study emphasises the benefits of taking physiological measurements of stress in epidemiological studies.     

Development and validation of an enzyme-linked immunosorbent assay for detection of cortisol in human saliva

Non-invasive measurement of cortisol in saliva is of prime importance as it represents a bioavailable neuroendocrine marker for stress. Therefore, in this study, we developed an enzyme immune assay that was suitable for salivary cortisol measurements. For that purpose, rabbit polyclonal antibody was raised against cortisol-3-CMO:BSA conjugate. The test was based on competition of liquid phase cortisol with conjugated cortisol on the solid phase. Primary antibody was used to bind available sites on the conjugate, which was proportional to numbers of cortisol in liquid phase. Biotinylated secondary anti-rabbit antibody was used to detect primary antibodies by addition of streptavidin peroxidase and substrate, respectively. Color formation was stopped and yellow color was read by a plate-reader spectrophotometer. Additionally, validated test was used to met all validation criteria including. Test developed was used to establish cortisol awakening response (CAR) in saliva samples collected in the morning after awakening (0, 15, 30, and 60^th min) from women (n = 4) and men (n = 4) at 8 or 4 different days, respectively. Diurnal cortisol levels were assessed (n = 8) at after awaking 60 min at morning, 12:00, 19:00, and 22:00 hr. In conclusion, an enzyme immunoassay test was successfully produced, validated and used for cortisol measurement in saliva samples.     

Day-to-day variation in saliva cortisol—Relation with sleep, stress and self-rated health

The objective was to examine the day-to-day variation in cortisol among healthy individuals and its relation to the time of saliva sampling, work, stress and fatigue. During 4 consecutive weeks, 14 office workers provided saliva samples (at awakening, 15 min after awakening and at bedtime) and made diary ratings for each day. Results showed a variation in cortisol values between participants but also within individuals. After controlling for the individual differences, results showed that low cortisol levels in the morning were associated with sleepiness at awakening and anxiety, exhaustion, and poor health the day before. High evening levels of cortisol were associated with symptoms of stress and poor self-rated health. Further analysis of the cortisol awakening response (CAR) showed that all participants had a mixture of both a positive and negative responses. During mornings with a negative response participants stayed in bed for a longer time after the initial awakening, which might be a sign of snoozing, thus missing the awakening response.     

Salivary cortisol and DHEA levels in the Korean population: age-related differences, diurnal rhythm, and correlations with serum levels

PURPOSE: The primary objective of this study was to examine the changes of basal cortisol and DHEA levels present in saliva and serum with age, and to determine the correlation coefficients of steroid concentrations between saliva and serum. The secondary objective was to obtain a standard diurnal rhythm of salivary cortisol and DHEA in the Korean population. MATERIALS AND METHODS: For the first objective, saliva and blood samples were collected between 10 and 11 AM from 359 volunteers ranging from 21 to 69 years old (167 men and 192 women). For the second objective, four saliva samples (post-awakening, 11 AM, 4 PM, and bedtime) were collected throughout a day from 78 volunteers (42 women and 36 men) ranging from 20 to 40 years old. Cortisol and DHEA levels were measured using a radioimmunoassay (RIA). RESULTS: The morning cortisol and DHEA levels, and the age- related steroid decline patterns were similar in both genders. Serum cortisol levels significantly decreased around forty years of age (p < 0.001, when compared with people in their 20s), and linear regression analysis with age showed a significant declining pattern (slope=-2.29, t=-4.297, p < 0.001). However, salivary cortisol levels did not change significantly with age, but showed a tendency towards decline (slope=-0.0078, t=-0.389, p=0.697). The relative cortisol ratio of serum to saliva was 3.4-4.5% and the ratio increased with age (slope=0.051, t=3.61, p < 0.001). DHEA levels also declined with age in saliva (slope=-0.007, t=-3.76, p < 0.001) and serum (slope=-0.197 t=-4.88, p < 0.001). In particular, DHEA levels in saliva and serum did not start to significantly decrease until ages in the 40s, but then decreased significantly further at ages in the 50s (p < 0.001, when compared with the 40s age group) and 60s (p < 0.001, when compared with the 50 age group). The relative DHEA ratio of serum to saliva was similar throughout the ages examined (slop=0.0016, t=0.344, p=0.73). On the other hand, cortisol and DHEA levels in saliva reflected well those in serum (r=0.59 and 0.86, respectively, p < 0.001). The highest salivary cortisol levels appeared just after awakening (about two fold higher than the 11 AM level), decreased throughout the day, and reached the lowest levels at bedtime (p < 0.001, when compared with PM cortisol levels). The highest salivary DHEA levels also appeared after awakening (about 1.5 fold higher than the 11 AM level) and decreased by 11 AM (p < 0.001). DHEA levels did not decrease further until bedtime (p=0.11, when compared with PM DHEA levels). CONCLUSION: This study showed that cortisol and DHEA levels change with age and that the negative slope of DHEA was steeper than that of cortisol in saliva and serum. As the cortisol and DHEA levels in saliva reflected those in serum, the measurement of steroid levels in saliva provide a useful and practical tool to evaluate adrenal functions, which are essential for clinical diagnosis.     

Impact of stress reduction instructions on stress and cortisol levels during pregnancy

This pilot study examined whether giving stress reduction (SR) instructions to pregnant women would be effective in regulating stress, mood, and cortisol levels during pregnancy. Forty-one predominantly low-income Latina women, receiving prenatal services at a public county hospital, completed measures of stress and mood (depressive symptoms, positive and negative affect) and provided morning and evening saliva samples to measure cortisol prior to and after receiving SR instructions. We hypothesized that adherence to these SR instructions would result in lower levels of stress, negative mood states, and cortisol levels when compared to baseline values. Repeated measures ANOVA analyses demonstrated significantly lower levels of stress (P < 0.001), lower symptoms of depression and negative affect (P < 0.001), and lower levels of morning cortisol (P = 0.01) under the SR condition, compared to baseline. Health behaviors that were engaged in during the SR condition and implications for prenatal health interventions are discussed.     

Relationship between salivary cortisol and depression in adolescent survivors of a major natural disaster

The purpose of this study was to determine the utility of salivary cortisol levels for screening mental states such as depression in adolescents following a natural disaster. We examined the relationship of salivary cortisol levels in adolescent survivors of the 2011 Tohoku Earthquake with the depression subscale of the 28-item General Health Questionnaire (GHQ). Subjects were 63 adolescent survivors (age = 14.29 years ± 0.51) who were administered the GHQ and provided saliva samples thrice daily (morning, afternoon and evening) over the course of 3 days. Based on the GHQ-depression subscores, subjects were divided into low and high depression groups. About 22 % of the subjects were classified into the high symptom group. When data collected over 3 days were used, a significant difference was observed between the two groups in the salivary cortisol levels at the evening time point as well the ratio of the morning/evening levels (p < 0.05). Analyzed by means of receiver-operating characteristic curves, the morning/evening ratios showed a good power in discriminating between subjects with and without depressive symptoms. Our study suggests that repeated measurement of salivary cortisol levels over 3 days has utility in screening for depressive states in adolescents following a natural disaster.     

Day-to-day friends’ victimization,aggression perpetration,and morning cortisol activity in late adolescents

This study investigates bidirectional associations between adolescents’ daily experiences of victimization and aggression perpetration within friendships. We investigated (a) across-day associations between victimization and aggression perpetration; (b) morning cortisol activity as a moderator of cross-day victimization and aggression links; and (c) potential sex differences in these patterns. For 4 consecutive days, 99 adolescents (M_age = 18.06, SD = 1.09, 46 females) reported whether they were victimized by or aggressive toward their friends. On three of these days, adolescents provided three morning saliva samples. Multilevel path analyses showed that across days, victimization and aggression were bidirectionally linked, but only for male adolescents. Additionally, for male adolescents, morning cortisol output (but not morning cortisol increase) moderated the association between victimization and next-day aggression; victimization predicted greater next-day aggression for boys with low, but not high, morning cortisol output. Findings implicate a physiological factor that may modify daily links between victimization and aggression in male adolescent friendships.     

Correlation between plasma and saliva adrenocortical hormones in response to submaximal exercise

This study examined the relationships between plasma and saliva adrenocortical hormones in response to long-duration submaximal exercise. In nine healthy, physically active, female volunteers, blood and saliva samples were taken at rest and every 30 min during a 120-min cycling trial at 50–55% VO_2max for cortisol and dehydroepiandrosterone (DHEA) analysis. Correlation analysis revealed a moderate but significant relationship between plasma and saliva cortisol (r = 0.35, P < 0.02) and plasma and saliva DHEA (r = 0.47, P < 0.001) during the submaximal exercise. When expressed in percent of resting values, the correlations between the plasma and saliva concentrations were higher for both hormones during the exercise (cortisol: r = 0.72; DHEA: r = 0.68, P < 0.001). The results thus suggest that, even under prolonged exercise conditions, non-invasive saliva samples may offer a practical approach to assessing pituitary–adrenal function, especially when compared with individual basal values.     

The relationship between long-term job strain and morning and evening saliva cortisol secretion among white-collar workers

The objective of this study was to assess long-term job strain impact on morning and evening salivary cortisol secretion. In all 77 white-collar workers (31% women; sample mean age, 42 years at baseline) volunteered to sample morning (immediately after waking up) and evening (10 p.m.) salivary cortisol for 7 consecutive days. By median split on aggregated self-reported isostrain from three consecutive questionnaires distributed in a period of approximately 3.5 years the participants were classified into a high or low long-term isostrain condition. Regardless of strain condition, there was a significant reduction in morning salivary cortisol secretion from the working week to the weekend, whereas evening salivary cortisol secretion showed no significant variation during the week. Although chronic isostrain did not affect the morning saliva cortisol measures, evening cortisol secretion was significantly elevated in the chronic high isostrain group throughout the whole week. The elevated evening cortisol measures associated with chronic high strain are concordant with the findings in other studies on long-term strain.     

Dissociative Symptoms and Cortisol Responses to Recounting Traumatic Experiences Among Childhood Sexual Abuse Survivors with PTSD

ABSTRACT

This study examined dissociative symptoms in relation to changes in evening salivary cortisol levels after recounting traumatic experiences among 49 women with PTSD for child sexual abuse (CSA). Each woman was interviewed to describe her sexual abuse and was assessed on acute dissociative symptoms in response to a recent stressful event in the previous month. Salivary cortisol was assessed during the interview using saliva samples taken immediately before and after the interview. Changes in cortisol levels were measured at one hour, 24 hours, and 48 hours after the interview. Acute dissociative symptoms were related to salivary cortisol levels 24 hours after the interview, with high dissociators showing elevated levels compared to low dissociators. These results suggest that dissociative symptoms in response to recent life stress are associated with cortisol dysregulation among women with PTSD for CSA.     

Adrenal hormone response and psychophysiological correlates under psychosocial stress in individuals with irritable bowel syndrome

ObjectiveIn this study, we investigated levels and relative ratios of adrenal hormones (including cortisol, dehydroepiandrosterone [DHEA], and DHEA-sulfate [DHEA-S]) and their psychophysiological correlates under acute psychosocial stress in individuals with irritable bowel syndrome (IBS).MethodsFifty-three college students participated in the study (male: 42, female: 11; mean age: 22.64 years), including 13 individuals with IBS (IBS group) and 40 individuals without IBS (control group). The participants were exposed to a standardized laboratory stressor, which included delivering a speech and performing a mental arithmetic task. We measured subjective stress levels and salivary cortisol, DHEA, and DHEA-S levels at relevant time points before, during, and after the tasks.ResultsDHEA-S level and the DHEA-S/DHEA ratio in the IBS group were significantly lower than those in the control group, and the cortisol/DHEA-S ratio in the IBS group was higher than that in the control group throughout the experiment. In the IBS group, the appraisal of a threat was positively correlated with cortisol levels (r = 0.61), and the appraisal of controllability was negatively correlated with cortisol levels (r = ? 0.64) and with the cortisol/DHEA ratio (r = ? 0.71). The control group showed a significant positive correlation between the appraisal of threat and cortisol levels (r = 0.32).ConclusionThe present study indicates that individuals with IBS had lower DHEA-S levels, and that their stressful cognitive appraisals under acute psychosocial stress caused the effects of cortisol to dominate. This adrenal hormone response may be involved in exacerbating abdominal symptoms in individuals with IBS.     

Responsiveness of the reproductive axis to a single missed evening meal in young adult males

Objectives: The male reproductive axis is responsive to energetic deficits, including multiday fasts, but little is known about brief periods of fasting (<24 hours). Reduced testosterone in low‐energy balance situations is hypothesized to reflect redirection of resources from reproduction to survival. This study tests the hypothesis that testosterone levels decrease during a minor caloric deficiency by assessing the effects of a single missed (evening) meal on morning testosterone in 23 healthy male participants, age 19–36. Methods: Participants provided daily saliva and urine samples for two baseline days and the morning following an evening fast (water only after 4 PM). Testosterone, cortisol, and luteinizing hormone were measured with enzyme immunoassays. Results: Fasting specimens had significantly lower overnight urinary luteinizing hormone (P = 0.045) and morning salivary testosterone than baseline (P = 0.037). In contrast to morning salivary testosterone, there was a significant increase in overnight urinary testosterone (P = 0.000) following the evening fast, suggesting an increase in urinary clearance rates. There was a marginal increase in overnight urinary cortisol (P = 0.100), but not morning salivary cortisol (P = 0.589). Conclusion: These results suggest the male reproductive axis may react more quickly to energetic imbalances than has been previously appreciated. Am. J. Hum. Biol., 2010. © 2010 Wiley‐Liss, Inc.     

Changes in salivary antimicrobial peptides,immunoglobulin A and cortisol after prolonged strenuous exercise

The aim of the present study was to examine whether amount of oral antimicrobial components, human β-defensin-2 (HBD-2), cathelicidin (LL-37), and immunoglobulin A (IgA), might be affected by prolonged strenuous exercise. Ten young male volunteers either exercised on recumbent ergometer at 75% [(V)\dot]\textO_2max \dot{V}{\text{O}}_{{2\max }} for 60 min (exercise session) or sat quietly (resting session). Saliva samples were obtained at 60-min intervals during sessions for measurements of saliva antimicrobial components (HBD-2, LL-37, and IgA), saliva cortisol and osmolality. Saliva flow rate was decreased and saliva osmolality was increased during the 60-min exercise. Saliva HBD-2 and LL-37 concentrations and secretion rates were increased during and after the exercise, whereas saliva IgA concentration and secretion rates were decreased after the exercise. Saliva cortisol was increased during and after the exercise. The areas under the curve of the time courses of saliva levels of HBD-2 and LL-37 were negatively correlated with those of cortisol levels in saliva. The present findings suggested that a single bout of prolonged strenuous exercise caused a transient increase in the oral HBD-2 and LL-37 levels.     

Allopregnanolone serum concentrations and diurnal cortisol secretion in women with premenstrual dysphoric disorder

Most prior studies in patients with premenstrual dysphoric disorder (PMDD) indicate a blunted hypothalamus–pituitary–adrenal axis function. However, the relationship between neuroactive progesterone metabolites, such as allopregnanolone, and hypothalamus–pituitary–adrenal (HPA) axis function in PMDD patients is relatively sparsely studied. The primary aims of this study were to assess diurnal variation in circulating cortisol and low-dose dexamethasone suppression in PMDD patients and healthy controls, and the relationship between these two HPA axis indices and allopregnanolone serum concentrations. Twenty-six women with prospectively defined PMDD and 30 healthy controls were recruited. Participants underwent diurnal sampling for cortisol serum concentrations and a low-dose dexamethasone suppression test. In addition, morning allopregnanolone serum concentrations were determined. There was no difference in diurnal secretion of cortisol and degree of dexamethasone suppression of cortisol between PMDD patients and healthy controls. However, PMDD patients with high allopregnanolone levels displayed blunted nocturnal cortisol levels in comparison with healthy controls who had low allopregnanolone serum concentrations. In women with PMDD, diurnal secretion of cortisol may be influenced by allopregnanolone levels of the luteal phase. This finding may be attributed to timing of blood sampling in the late luteal phase as well as the individual level of allopregnanolone but could potentially explain the discrepancies in results between studies examining HPA axis function in women with PMDD.     

Effects of long-term inhaled corticosteroids on adrenal function in patients with asthma.

BACKGROUND: Inhaled corticosteroids (ICSs) are effective asthma controllers, but long-term use could lead to adverse effects. Objective: To examine adrenal responsiveness of patients with persistent asthma treated with long-term ICSs. METHODS: Morning plasma cortisol levels before and 30 minutes after adrenocorticotropic hormone (ACTH) (1 microg intravenously) stimulation were compared. Primary end points included mean prestimulation and poststimulation cortisol levels; secondary end points included morning cortisol level of 5 microg/dL or less, post-ACTH stimulation cortisol level of 18 microg/dL or less, and/or a net change of 7 microg/dL or less from baseline. RESULTS: A total of 103 asthmatic patients (29 in the triamcinolone acetonide group, 18 in the flunisolide group, 45 in the fluticasone propionate group, and 11 in the oral corticosteroids group [positive controls]) completed the study. Mean daily ICS doses and durations were as follows: triamcinolone acetonide: 448 microg for 36 months; flunisolide: 1,181 microg for 41 months; and fluticasone propionate: 745 microg for 19 months. Eleven of 30 patients taking high-dose ICSs (10 of 28 taking fluticasone propionate and 1 of 2 taking flunisolide) had both low morning cortisol levels and abnormal post-ACTH stimulation cortisol levels. Few patients taking lower doses of any ICS had abnormal results. CONCLUSIONS: Patients who require long-term treatment with high-dose ICSs may have abnormal morning plasma cortisol levels and reduced responsiveness to ACTH stimulation. Careful monitoring of adrenal function should be considered in such patients.     

Patterns of salivary cortisol levels can manifest work stress in emergency care providers

To develop objective assessments of work fatigue, we investigated the patterns of changes in salivary cortisol levels in emergency care providers working extended work shifts. Fourteen subjects, comprising seven physicians and seven physician assistants, provided unstimulated saliva samples at regular intervals over the course of a 24-h work shift and over their subsequent free day. There was a significant time effect, with early morning cortisol levels being significantly attenuated following the work shift. Native diurnal variations varied by gender, with the female subjects manifesting greater cortisol levels. Physicians also had higher cortisol profiles even though their wake–rest cycles were similar to those of the physician assistants. Our results suggest that temporal changes, as well as diurnal similarities, in the salivary cortisol patterns can reflect work-related stress and recovery. In particular, early morning cortisol levels may manifest individual reactivity to work stressors as well as sleep deprivation.     

The Impact of Asthma Control on Salivary Cortisol Level in Adult Asthmatics

Asthma is a chronic disease causing psychological stress which leads to the activation of hypothalamus-pituitary-adrenal axis. The purpose of this study is to compare morning salivary cortisol levels in persistent asthma patients according to their disease severities and control status. Total 206 adult asthma patients were recruited from four university hospitals. Spirometry, questionnaire of Asthma Quality of Life (AQOL) and Asthma Control Test (ACT) were completed, and saliva samples were collected prospectively to measure morning cortisol level. The mean patient age was 56.5±15.3 years with mean asthma duration of 9.1±11.1 years. Sixty five patents (31.6%) were classified as mild persistent asthma, and 141 patients (68.4%) were classified as moderate persistent asthma according to the Expert Panel Report 3. The mean predicted FEV1 was 88.8%±18.4%, and the methacholine PC20 was 9.6±8.5 mg/mL in all study population. The mean ACT score for all patients was 19.9±3.6, and there were 71 (34.5%) patients in poorly controlled and 135 (65.5%) in well controlled asthma. The poorly controlled asthma patients were characterized by significantly lower FEV1 (84.6%±17.6% vs 91.1%±18.5%, P=0.018), lower AQOL scores (46.0±13.9 vs 73.8±26.3, P<0.001), and lower salivary cortisol levels (0.14±0.08 vs 0.18±0.11 µg/dL, P=0.04) compared to well controlled asthma. The ACT score was significantly related to salivary cortisol levels (P=0.034) after adjusting for age. There was no significant difference in salivary cortisol levels (0.17±0.12 vs 0.16±0.08, P=0.725) when analyzed according to the dose of used corticosteroid and lung function. Asthma control status affects morning salivary cortisol level. Measuring the morning salivary cortisol level might be a simple and new way to assess asthma control status.     

Salivary cortisol, APOE-ε4 allele and cognitive decline in a prospective study of older persons

Objective

We determined whether salivary cortisol levels were associated with cognitive decline at follow-up in older persons and whether this association was modified by the APOE-ε4 allele.

Methods

Within the Longitudinal Aging Study Amsterdam (LASA), a population-based prospective cohort study, 911 persons (74.5 ± 7.2 years, 46.4% male) collected salivary cortisol in the morning and late in the evening. At baseline and after 4 years of follow-up, global cognitive functioning, verbal memory performance, and processing speed were assessed. The longitudinal associations between cortisol measures and cognitive decline were estimated using linear mixed models, adjusted for potential confounders and the modifying role of the APOE-ε4 allele was examined.

Results

Lower morning cortisol levels, higher evening cortisol levels, and flattened diurnal variability of cortisol levels were associated with increased risk for memory decline in APOE-ε4 carriers but not in non-carriers.

Conclusion

Our findings suggest that in this older non-demented population APOE-ε4 carriers may be more vulnerable to the potential detrimental effect of hypothalamic-pituitary-adrenal axis dysfunction on verbal memory performance.