Physiologic markers of chronic stress in premenopausal,middle-aged women

OBJECTIVE: The purpose of this study was to identify physiological markers of chronic stress in middle-aged women that can be assessed simply and are thus feasible for introduction into large-scale, epidemiologic studies of aging. METHODS: Subjects were 40 nonsmoking, premenopausal women between the ages of 42 and 52 years, 20 of whom were chronically stressed because of undergoing a divorce or separation and 20 of whom were nonstressed because of being in stable marriages. Stressed and nonstressed women were matched for age, ethnicity, and education. Hypotheses focused on morning and evening salivary cortisol, overnight urinary catecholamines, cortisol, and testosterone, and platelet catecholamines. RESULTS: Relative to the nonstressed control subjects, the stressed women had elevated evening (9 PM) salivary cortisols, a finding that was observed on both days (mixed effects model: effect = 0.44; se = 0.14, p =.003). Support for the importance of the HPA axis was provided by the observation that the stressed women had less suppression of salivary cortisol in response to low-dose dexamethasone. Contrary to our hypothesis that stressed women would have lower overnight urinary testosterone, they had higher testosterone on day 2 (stressed = 0.76 ng/mg, nonstressed = 0.55 ng/mg; p =.04). Post hoc repeated measures analysis revealed a significant group effect over all time periods of observation (F = 5.48, p =.03, df = 1,18). Stressed women had a nonsignificant trend toward elevated platelet catecholamines. No association was found for overnight urinary catecholamines or cortisol. CONCLUSIONS: Promising markers of marital upheaval in middle-aged women are evening salivary cortisol and urinary testosterone from a first morning void. Replication of these findings with the same and different chronic stressors and with women of older ages is needed. The low cost and minimal burden of these potential markers makes it feasible to introduce them into large-scale epidemiologic studies of health in aging women.     

Morningness and eveningness: the free cortisol rise after awakening in "early birds" and "night owls"

We investigated salivary cortisol profiles in the first hour after awakening in morning versus evening chronotypes. Chronotypes were defined by Horne and Ostberg's Owl-and-Lark-Questionnaire. In a sample of 112 healthy, day-active young men, we identified 9 morning and 29 evening chronotypes. Saliva samples were collected 0, 30, 45, and 60min after awakening on 2 consecutive days. Log-transformed cortisol levels were analyzed with General Linear Model procedures (GLMs) and awakening time and sleep duration were entered as covariates. On both days, a significant main effect of chronotype emerged (both p=0.02), and this effect could not be explained by differences in awakening time or sleep duration. The present data support the idea that morning relative to evening chronotypes might show higher cortisol levels in the first hour after awakening. In sum, individual chronotype should be acknowledged as one further possible source of interindividual variability in the cortisol rise after awakening.     

Morningness-eveningness and early-morning salivary cortisol levels.

The purposes of this exploratory study were: (1) to describe a 2-h segment of the early-morning salivary cortisol levels of morning (M) and evening (E) types of healthy, day-active adults on one morning; and (2) to compare selected demographic and sleep characteristics. The sample consisted of 20 subjects, aged 23-39 years, 10 of each type. Measures included: morningness-eveningness questionnaire score, demographic information, self-report sleep characteristics, and self-report of well-being. Beginning with time of arising, seven salivary samples were collected at approximately 20-min intervals. Among the sleep variables, bedtime (p = 0.005), time of mid-sleep (p = 0.002), and arising time (p = 0.043) were later in the E group as compared to the M group. Six M and one E subject awoke spontaneously on the morning of sampling without an awakening aid (p = 0.018). Even though total hours of sleep were comparable between groups, E subjects reported feeling less rested in the morning (p = 0.019). Although mean M group salivary cortisol levels were greater than mean E group levels for each sampling time, there were no significant group differences. Eight M subjects reached a sampling period salivary cortisol peak by 50 min after arising, contrasted with six E subjects who reached their peak at that time. These preliminary findings suggest that E types demonstrate lower morning arousal and a delay in their early-morning peak of salivary cortisol relative to M types. Further study is needed to explore the relationship between M and E types, their sleep-wake patterns, and cortisol secretion patterns.     

Menopause, mild psychological stress and salivary cortisol: influence of long-term hormone replacement therapy (HRT)

OBJECTIVE: Aim of the present study was to examine the adrenocortical activity in basal condition and following a mild stress exposure in long-term HRT-treated menopausal women. Menopausal women, long term users of HRT (14 subjects) were compared both to menopausal women who had never used HRT (14 subjects) and young pre-menopausal women (14 subjects). STUDY DESIGN: Morning and evening salivary cortisol secretion was measured in samples collected twice a day (08:00 in the morning and 08:00 in the evening). Mild stress response was evoked by administration of the Stroop color-word test (CWT). Salivary cortisol was measured immediately before the start, 15, 30 and 45 min after the completion of the test. RESULTS: Menopause appears not to be associated with an impairment of cortisol circadian fluctuation. Long-term use of HRT in menopause attenuated HPA activity either in basal condition or in response to mild stress exposure. With regard to the CWT performance, all menopausal women took significantly longer than young women to perform the test. However, long-term HRT significantly reduced the number of errors made during the test. CONCLUSIONS: The present study suggested that long-term HRT could help menopausal patients to cope with mild stress and to improve mental performances.     

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.     

Job strain and anger expression predict early morning elevations in salivary cortisol

OBJECTIVE: The objectives of this study were to test the hypothesis that high job demands and low job control (job strain) are associated with elevated free cortisol levels early in the working day and with reduced variability across the day and to evaluate the contribution of anger expression to this pattern. METHODS: One hundred five school teachers (41 men and 64 women) classified 12 months earlier as high (N = 48) or low (N = 57) in job strain according to the demand/control model sampled saliva at 2-hour intervals from 8:00 to 8:30 hours to 22:00 to 22:30 hours on a working day. Anger expression was assessed with the Speilberger State-Trait Anger Expression Inventory, and negative affect was also measured. RESULTS: Free cortisol was significantly elevated at 8:00 to 8:30 hours in the high job strain group but not at later times of the day or evening. After adjustment for age and negative affect, cortisol was an average of 21.7% higher early in the working day in the high job strain group. This effect was significantly greater in high job strain teachers, who also reported high anger-out. The cortisol decline from morning to evening was greater in the high than low job strain individuals. Independently of job strain, women had a higher cortisol concentration at 8:00 to 8:30 hours than men, whereas cortisol concentration was greater in men than women in the middle of the working day between 12:00 and 16:30 hours. CONCLUSIONS: Job strain is associated with elevated free cortisol concentrations early in the working day but not with reduced cortisol variability. The interaction with outward anger expression suggests that individual characteristics modulate the impact of chronic work stress on the hypothalamic-pituitary-adrenocortical system.     

A prospective study of diurnal cortisol responses to the social experience of school transition in four-year-old children: anticipation, exposure, and adaptation

This study examined psychosocial influences on hypothalamic-pituitary-adrenal axis activity in 105 4-year-old children transitioning to primary school. Measuring before, during, and after school transition over a period of up to 12 months, salivary cortisol was assessed on awakening and early evening. Parents reported child temperament and teachers recorded adaptive behavior. Whilst cortisol at awakening and early evening increased from baseline to school transition, effects were not significant. A significant decrease occurred between transition and follow-up and from baseline to follow-up for both awakening and evening cortisol. Poorer effortful control was associated with high morning and steeper diurnal slope of cortisol at transition whilst surgency/extroversion was associated individually with greater morning and evening cortisol at transition and adaptation. Greater increase in internalizing social isolation during the first 6 months of school in more surgent/extrovert children predicted higher morning and evening cortisol at follow-up. This study is the first to explore these adaptive relationships over a 12-month period and supports social isolation over time as a key element in developmental endocrine activation.     

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.     

Sequence and Seasonal Effects of Salivary Cortisol

Abstract

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 I 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.     

Work family balance, stress, and salivary cortisol in men and women academic physicians

Background: The stress of medical practice has been recurrently studied, but work- and family-related determinants of health by gender remain under researched. Purpose: To test the hypothesis that cortisol excretion would be affected by the perceived severity of total workload imbalance. Method: By hierarchical regression analysis, the associations between work-family balance and diurnal salivary cortisol levels by sex in academic physicians (n = 40) were investigated. Results: Men physicians reported more paid work hours per week than women physicians and women more time in childcare, but their total working hours were similar. Controlling for sex and age, the mean of the diurnal cortisol release was associated with a combined effect of sex and responsibility at home. When morning cortisol, sex, and children at home were held constant, cortisol levels in the evening were associated with responsibility at home without significant gender interaction. Conclusion: With increasing responsibility at home, women and men reacted differently with regard to cortisol responses over the day. However, in the evening, controlling for the morning cortisol, these gender differences were not as obvious. These findings highlight traditional gender patterns among both women and men physicians in the challenge of finding a balance between work and family.     

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.     

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.     

Salivary cortisol, stress and mood in healthy older adults: the Zenith study

The aims of this study were to investigate the relationship between salivary cortisol, stress and mood and to look at the circadian rhythms of positive (PA) and negative (NA) mood in older adults. The participants were 41 healthy adults aged 55-69 years, recruited in Northern Ireland as part of the European Commission-funded Zenith project. Salivary cortisol samples were obtained twice a day (2.30 p.m. and 10.30 p.m.) for 7 consecutive days in conjunction with momentary measures of positive (PA) and negative mood (NA), using PANAS and a trait measure of perceived stress (Perceived Stress Scale). Salivary cortisol levels were measured using an enzyme-linked immunoassay kit. Higher perceived stress levels were associated with lower afternoon PA (r=-0.46, p=0.003) and higher afternoon (r=0.43, p=0.007) and evening (r=0.45, p=0.004) NA. Lower afternoon PA was correlated with higher evening cortisol concentrations (r=-0.47, p=0.002). Greater afternoon PA variability was associated with higher evening cortisol concentrations (r=0.38, p=0.015). A high intra-class correlation between cortisol and positive mood was found (r=0.67, p=0.009). Previously established rhythms for positive and negative mood were confirmed. Interestingly, there was no association between salivary cortisol levels and perceived stress in these healthy older adults. Further, more extensive research is required to better understand the apparent interplay between these variables and ageing.     

Behavioral and neuroendocrine responses in shy children

Previous research has shown that infants who display a high frequency of motor activity and negative affect at 4 months of age are likely to be behaviorally inhibited toddlers. We examined social behaviors, maternal report of temperament, salivary cortisol, and baseline startle responses at age 4 in a sample of children, some of whom displayed a high frequency of motor activity and negative affect at 4 months of age. Infants who displayed this temperamental profile were reported by their mothers as more shy at age 4 compared with other children. We also found that 4-year-olds who displayed a high frequency of wary behavior during peer play exhibited relatively high morning salivary cortisol, were reported as contemporaneously shy by their mothers, and were behaviorally inhibited at 14 months of age. There were no significant relations found between baseline startle and morning salivary cortisol and measures of shyness at age 4. We speculate that high levels of cortisol in shy children may induce changes in the amygdala, exacerbating their fearfulness. © 1997 John Wiley & Sons, Inc. Dev Psychobiol 30: 127–140, 1997     

Impact of acute sleep restriction on cortisol and leptin levels in young women

Sleep restriction alters hormone patterns and appetite in men, but less is known about effects on women. We assessed effects of overnight sleep restriction on cortisol and leptin levels and on appetite in young women. Participants' baseline sleep duration and eating habits were monitored for a week before the study. Salivary cortisol and leptin were sampled from fifteen healthy women (aged 18-25) during two consecutive days: first after a 10 h overnight sleep opportunity (Baseline day) and then after a night including only 3 h sleep (Post sleep-restriction day). Participants also completed appetite questionnaires on both days. Sleep restriction significantly reduced morning cortisol levels (p = 0.02), elevated morning leptin levels (p = 0.04), elevated afternoon/evening cortisol area under the curve values (p = 0.008), and slowed the decline in cortisol concentration during the day (p = 0.04). Hunger and craving scores did not differ significantly between days. A single night of restricted sleep affected cortisol rhythms and morning leptin levels in young women.     

Burnout, perceived stress, and cortisol responses to awakening

OBJECTIVE: The effects of burnout and perceived stress on early morning free cortisol levels after awakening were investigated in a group of teachers. Previous studies revealed that cortisol levels show a significant increase after awakening, with high intraindividual stability. METHODS: Sixty-six teachers from local public schools (42 women and 24 men, mean age 42+/-5 years) were asked to sample saliva for cortisol analysis on 3 consecutive days. On each day, cortisol levels were measured at the time of awakening and 15, 30, and 60 minutes thereafter. On the night before the third day, subjects took 0.5 mg dexamethasone orally for testing glucocorticoid feedback inhibition. Burnout and perceived stress were measured by three different questionnaires. RESULTS: Perceived stress correlated with increases of cortisol levels during the first hour after awakening after dexamethasone pretreatment. In addition, teachers scoring high on burnout showed lower overall cortisol secretion on all sampling days, and a higher suppression of cortisol secretion after dexamethasone administration. In the subgroup of teachers with both high levels of perceived stress and high levels of burnout, a lower overall cortisol secretion was observed on the first 2 days, with stronger increases during the first hour after awakening after dexamethasone suppression. This subgroup also showed the lowest self-esteem, the highest external locus of control, and the highest number of somatic complaints. CONCLUSIONS: These results demonstrate differential effects of burnout and perceived stress on hypothalamic-pituitary-adrenal axis regulation.     

Heritability of Daytime Cortisol Levels in Children

Individual differences in the level of the stress hormone cortisol play a prominent role as an explanatory variable in studies on psychopathology. Relatively few studies have paid attention to individual differences in cortisol levels and the etiology of these differences, in particular their possible genetic basis. All these studies have been in adults. The aim of this study was to estimate genetic and environmental influences on basal cortisol levels in 12-year-old children. To this end, four samples of salivary cortisol were collected on two consecutive days in a sample of 180 twin pairs. Low correlations were found between cortisol levels at different points in time during the day. A significant genetic contribution was found to the variation of basal cortisol levels in the morning and afternoon samples, but not in the evening sample. Heritability did not differ for boys and girls and was highest (60%) for cortisol levels during the sample taken about 45 minutes after awakening. This cortisol awakening response provides a useful endophenotype in the search for genes that may affect hypothalamic-pituitary adrenocortical functioning in children.     

Correlations between cortisol level and internalizing disposition of young children are increased by selecting optimal sampling times and aggregating data

To determine the optimal time for testing the association between personality traits and cortisol levels, and the number of sampling days needed for reliable results to be obtained for preschool-aged children, ambulatory salivary sampling for cortisol was performed on 39 preschoolers at four different times for 10 consecutive school days. A repeated-measure ANOVA revealed a significant day effect, time effect, and day by time interaction. Further tests of day effect revealed that within-subject cortisol levels differed significantly in the early morning, early afternoon, and late afternoon cortisol data, but not in the late morning; group average levels of cortisol assessed in the early mornings are significantly different among the days, so are the ones measured in early and late afternoon. Mid-afternoon cortisol levels showed the most significant day effect and the highest correlation with internalizing disposition. In addition, the probability of finding significant correlations between cortisol levels and internalizing disposition increased with a greater number of aggregated cortisol measures. The tentative conclusion is that to avoid under-representation of the correlations between cortisol levels and personality variables, both sampling time selection and data aggregation are important.     

Patients with atopy exhibit reduced cortisol awakening response but not cortisol concentrations during the rest of the day

It has been documented that cortisol release in response to acute stressors is reduced in patients with atopic dermatitis, allergic rhinitis, and other atopic diseases compared to that in healthy subjects. We aimed to test the hypothesis that atopic patients exert reduced salivary cortisol awakening response (CAR) in comparison with healthy subjects. The hypothesis was tested on a stressful and a relax day selected subjectively. Moreover, we evaluated the impact of trait anxiety. The sample consisted of 60 subjects, out of which 28 were patients with atopy and 32 healthy volunteers of both sexes. Saliva samples were collected in the morning to evaluate CAR as well as in the early afternoon and evening to look at cortisol concentrations during the rest of the day. The results showed reduced CAR in atopic patients compared to that in healthy subjects. This effect was modulated by sex with a significant difference observed in males. While CAR was reduced, atopic patients had unchanged cortisol concentrations throughout the day. The evening cortisol was even higher in atopic patients. If the subjects were stratified according to the trait anxiety, no significant differences in CAR between high and low anxiety were observed. No differences in cortisol variables including CAR were observed between the stressful and relax day. In conclusion, this study presents evidence on reduced CAR suggesting an insufficient HPA axis reactivity in atopy. Furthermore, the data in atopic patients demonstrate that reduced HPA axis reactivity does not necessarily mean lower cortisol concentrations throughout the day. This might be of relevance to immune system function and the course of the disease.

     

Diurnal variation of the startle reflex in relation to HPA-axis activity in humans

Diurnal variation of baseline startle amplitude was examined in 14 normal inpatients on a research unit where behavioral activity and environmental stimuli were highly controlled. We tested a hypothesized association between diurnal variations of salivary cortisol and reflex amplitude by recording acoustic startle eyeblinks shortly before bedtime, when cortisol was near its lowest daily level, and just after awakening, when cortisol was at its peak. Results showed that startle eyeblinks were greater during evening than morning sessions, whereas the opposite was true for cortisol levels. Skin conductance levels and reaction time performance also increased from morning to evening. These findings are consistent with accumulating evidence suggesting a possible link between startle reactivity and hypothalamic-pituitary-adrenal axis activity, and an association between diurnal variations in endogenous arousal and startle amplitude.