To determine whether there is a relationship between depressive symptoms and cortisol assessed at first morning awakening, 6PM, and 9PM in a population-based sample of midlife women. If this relationship is not linear, we aim to test whether this relationship is nonlinear, only present in those with more severe depressive symptoms, better accounted for by diurnal slope, or only apparent under uncontaminated conditions.
We investigated the cross-sectional association between cortisol and depressive symptoms, assessed by the Center for Epidemiological Studies Depression Scale (CES-D) in 408 midlife women (45.7% African-Americans, 54.3% white; mean age = 50.4) participating in the Chicago site of the Study of Women’s Health Across the Nation (SWAN).
Diurnal cortisol slope is significantly flatter for women with higher CES-D scores than for less depressed women (p<.05 for the interaction). This relationship remains significant even after adjusting for age, smoking status, race, education, income, menopausal status, hormone replacement therapy (HRT), body mass index (BMI), medications, and wake time as well as possibly contaminating factors including physical activity, smoking, eating, or caffeine or alcohol consumption prior to saliva collection. Results using depression assessed categorically (CES-D cutoff ≥ 16) were similar to those using continuous depression in both unadjusted and adjusted analyses (p=.005 for the interaction of CES-D by time).
In this population-based sample of midlife women, greater depressive symptoms were associated with a significantly flatter diurnal cortisol slope than those with fewer symptoms, even after adjusting for covariates and possibly contaminating behaviors.
diurnal cortisol; depressive symptoms; midlife women; women’s health
Neuroendocrine abnormalities, such as activation of the hypothalamic-pituitary-adrenal (HPA) axis, are associated with obesity; however, few large-scale population-based studies have examined HPA axis and markers of obesity. We examined the cross-sectional association of the cortisol awakening response (CAR) and diurnal salivary cortisol curve with obesity. The Multi-Ethnic Study of Atherosclerosis (MESA) Stress Study includes 1,002 White, Hispanic, and Black men and women (mean age 65±9.8 years) who collected up to 18 salivary cortisol samples over 3 days. Cortisol profiles were modeled using regression spline models that incorporated random parameters for subject-specific effects. Cortisol curve measures included awakening cortisol, CAR (awakening to 30 minutes post-awakening), early decline (30 minutes to 2 hours post-awakening), late decline (2 hours post-awakening to bedtime), and the corresponding areas under the curve (AUC). Body-mass-index (BMI) and waist circumference (WC) were used to estimate adiposity. For the entire cohort, both BMI and WC were negatively correlated with awakening cortisol (p<0.05), AUC during awakening rise and early decline and positively correlated to the early decline slope (p<0.05) after adjustments for age, race/ethnicity, gender, diabetes status, socioeconomic status, beta blockers, steroids, hormone replacement therapy and smoking status. No heterogeneities of effects were observed by gender, age, and race/ethnicity. Higher BMI and WC are associated with neuroendocrine dysregulation, which is present in a large population sample, and only partially explained by other covariates.
adiposity; hypothalamic-pituitary-adrenal (HPA) axis; salivary cortisol; diurnal cortisol; cortisol awakening response; epidemiology; obesity; body mass index; waist circumference; epidemiology
The purpose of the study was to assess the impact of job strain and sleep quality on the diurnal pattern of cortisol reactivity, measured by awakening and evening (10 PM) saliva cortisol. The sample consisted of 76 British white-collar workers (24 women, 52 men; mean age 45.8 years). Sleep quality and job strain were assessed in a survey distributed just before the cortisol sampling. Both input variables were dichotomized about the median and factorial ANOVA was used for the statistical analysis. Low sleep quality was significantly associated with lower morning cortisol secretion. While job strain had no main effects on the cortisol reactivity there was a significant interaction effect between the input variables on morning cortisol secretion. These findings tentatively support the hypothesis that lack of sleep for workers with high job strain may result in a flattened diurnal cortisol reactivity.
cortisol; job strain; sleep quality
Racial/ethnic minorities experience persistent health disparities due in part to their exposure to chronic SES and psychosocial risk. The hypothalamic-pituitary-adrenal axis and its hormonal end product, cortisol, are believed to mediate the associations between chronic stress and poor health. In this study, racial/ethnic differences in diurnal salivary cortisol rhythms in 179 preadolescent youths and the contributing roles of SES risk, psychosocial risk, perceived discrimination, harsh parenting, and parental monitoring were examined. The analyses revealed racial/ethnic differences in diurnal cortisol rhythms, with African Americans having significantly flatter morning-to-evening cortisol slopes than Caucasians and with Latinos having significantly lower evening cortisol levels than Caucasians. Greater psychosocial risk and less parental monitoring were associated with flatter cortisol slopes. Racial/ethnic differences on the cortisol measures persisted when controlling for SES, psychosocial risk, and parenting quality. The need to assess chronic risk across the lifespan and disentangle possible genetic from environmental contributors is discussed.
cortisol; race/ethnicity; preadolescent youths; psychosocial risk; parental monitoring
Research in adult populations has highlighted sex differences in cortisol concentrations and laboratory pain responses, with men exhibiting higher cortisol concentrations and reduced pain responses compared with women. Yet, less is known about the relationship of cortisol concentrations to pain in children.
This study examined associations between sex, cortisol, and pain responses to laboratory pain tasks in children.
Salivary cortisol samples from subjects aged 8 to 18 years were obtained at baseline after entering the laboratory (SCb), after the completion of all pain tasks (SC1), and at the end of the session (SC2), 20 minutes later. Blood cortisol samples were also taken after completion of the pain tasks (BC1) and at the end of the session (BC2), 20 minutes later. Subjects completed 3 counterbalanced laboratory pain tasks: pressure, heat, and cold pressor tasks. Pain measures included pain tolerance, and self-reported pain intensity and unpleasantness for all 3 tasks.
The study included 235 healthy children and adolescents (119 boys, 116 girls; mean age, 12.7 years; range, 8–18 years; 109 [46.4%] were in early puberty; 94 [40.0%] white). Salivary and blood cortisol levels were highly correlated with each other. Salivary cortisol levels for the total sample and for boys and girls declined significantly from SCb to SC1 (P < 0.01), although there were no significant changes from SC1 to SC2. No significant sex differences in salivary or blood cortisol levels were evident at any assessment point. Separate examination of the cortisol–laboratory pain response relationships by sex (controlling for age and time of day) suggested different sex-specific patterns. Higher cortisol levels were associated with lower pain reactivity (ie, increased pressure tolerance) among boys compared with girls at SC1, SC2, and BC1 (SC1: r = 0.338, P = 0.003; SC2: r = 0.271, P = 0.020; and BC1: r = 0.261, P = 0.026). However, higher cortisol levels were related to higher pain response (ie, increased cold intensity [BC2: r = 0.229, P = 0.048] and unpleasantness [BC1: r = 0.237, P = 0.041]) in girls compared with boys.
These findings suggest important sex differences in cortisol–pain relationships in children and adolescents. Cortisol levels were positively associated with increased pain tolerance in boys and increased pain sensitivity in girls.
pain; children; cortisol; sex differences
Associations of cortisol and depression vary at different life-stages, yet population-based, prospective studies are scarce. We aimed to assess associations of morning cortisol with depressive symptoms in mid-life taking account of lifetime psychological health.
Participants were 5,403 men and women from the 1958 British Birth Cohort whose salivary cortisol was assessed at 45y (45min after waking (T1) and 3h later (T2)) and who completed the 5-item Mental-Health Index (MHI-5) about depressive symptoms at age 50y. Lifetime psychological health was identified from child and adult measures.
For women, higher T2 cortisol at 45y predicted depression (MHI-5 scores ≤52) at 50y (odds ratio [OR]=1.17; 95% confidence intervals [CI] 1.05,1.30 per standard deviation increase in T2 cortisol), attenuating when adjusted for current (45y) and previous (7-42y) psychological health (OR=1.11; 95% CI 0.98, 1.24). Similarly, an association in women of flatter cortisol delta (T2-T1) with depressive symptoms at 50y weakened after adjustment for current (45y) and previous (7-42y) psychological health. For men, lower T2 cortisol at 45y predicted greater depressive symptoms at 50y and the association strengthened when adjusted for lifetime psychological health. Likewise, lower cortisol AUC predicted higher risk of depression for men after adjusting for prior psychological health (OR=0.85; CI 0.72, 1.00). Associations were largely unaltered by control for covariates.
In women, higher cortisol in late morning at 45y is prospectively associated with depressive symptoms at 50y through a link with lifetime psychological health. In men, lower cortisol predicts subsequent symptoms, independent of depressive history.
Maternal salivary cortisol was measured at weekly intervals from 24 to 38 weeks gestation. The total sample consisted of 120 women enrolled in staggered intervals in such a way as to generate weekly measures of salivary cortisol during the latter half of pregnancy. Hierarchical linear modeling revealed the expected increase in unbound maternal cortisol during this period, with a slight deceleration in rate of increase at 33 weeks gestation. Women carrying male fetuses had higher levels of salivary cortisol initially as compared to women carrying female fetuses; at 30 weeks gestation there was cross-over such that higher maternal cortisol was observed in women carrying female fetuses beyond this time and through term. Results highlight the importance of considering fetal sex as a moderator of contemporaneous and predictive associations between maternal cortisol and prenatal or postnatal development.
cortisol; pregnancy; sex differences; male vulnerability; HPA axis
To examine the cross-sectional association of diurnal salivary cortisol curve components and urinary catecholamines with diabetes status.
Up to 18 salivary cortisol samples over 3 days and overnight urinary catecholamines were collected from 1,002 participants in the Multi-Ethnic Study of Atherosclerosis. Diabetes was defined as a fasting blood glucose ≥126 mg/dL or medication use. Cortisol curve measures included awakening cortisol, cortisol awakening response (CAR), early decline, late decline, and cortisol area under the curve (AUC). Urinary catecholamines included epinephrine, norepinephrine, and dopamine.
Participants with diabetes had significantly lower CAR (β=−0.19; 95% CI: −0.34 to −0.04) than those without diabetes in multivariable models. While men with diabetes had a non-significant trend toward lower total AUC (β=−1.56; 95% CI: −3.93 to 0.80), women with diabetes had significantly higher total AUC (β=2.62; 95% CI: 0.72 to 4.51) (p=0.02 for interaction) compared to those without diabetes. Men but not women with diabetes had significantly lower urinary catecholamines, compared to those without diabetes (p<0.05).
Diabetes is associated with neuroendocrine dysregulation, which may differ by sex. Further studies are needed to determine the role of the neuroendocrine system in the pathophysiology of diabetes.
diabetes; hypothalamic-pituitary-adrenal (HPA) axis; salivary cortisol; catecholamines; epidemiology
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, 11AM, 4PM, 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).
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 11AM level) and decreased by 11AM (p < 0.001). DHEA levels did not decrease further until bedtime (p = 0.11, when compared with PM DHEA levels).
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.
Saliva cortisol; saliva DHEA; correlation; age-related changes; diurnal rhythm
The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been reported to be involved in obesity-associated metabolic disturbances in adults and in selected populations of adolescents. The aim of this study was to investigate the association between morning adrenocorticotropic hormone (ACTH) and cortisol levels and cardiovascular risk factors in overweight or obese Caucasian children and adolescents.
This cross-sectional study of 450 obese children and adolescents (aged 4 to 18 years) was performed in a tertiary referral center. ACTH, cortisol, cardiovascular risk factors (fasting and post-challenge glucose, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, and hypertension) and insulin resistance were evaluated. All analyses were corrected for confounding factors (sex, age, puberty, body mass index), and odds ratios were determined.
ACTH and cortisol levels were positively associated with systolic and diastolic blood pressure, triglycerides, fasting glucose and insulin resistance. Cortisol, but not ACTH, was also positively associated with LDL-cholesterol. When adjusted for confounding factors, an association between ACTH and 2 h post-oral glucose tolerance test glucose was revealed. After stratification according to cardiovascular risk factors and adjustment for possible confounding factors, ACTH levels were significantly higher in subjects with triglycerides ≥90th percentile (P <0.02) and impaired fasting glucose or glucose tolerance (P <0.001). Higher cortisol levels were found in subjects with blood pressure ≥95th percentile and LDL-cholesterol ≥90th percentile. Overall, the highest tertiles of ACTH (>5.92 pmol/l) and cortisol (>383.5 nmol/l) although within the normal range were associated with increases in cardiovascular risk factors in this population.
In obese children and adolescents, high morning ACTH and cortisol levels are associated with cardiovascular risk factors. High ACTH levels are associated with high triglyceride levels and hyperglycemia, while high cortisol is associated with hypertension and high LDL-cholesterol. These specific relationships suggest complex mechanisms through which the HPA axis may contribute to metabolic impairments in obesity, and merit further investigations.
ACTH; cardiovascular risk; cortisol; glucose; hypertension; lipids; obesity; pediatric
Prenatal cocaine exposure (PCE) is associated with blunted stress responsivity within the extrauterine environment. This study investigated the association between PCE and diurnal salivary cortisol levels in preadolescent children characterized by high biological and/or social risk (N = 725). Saliva samples were collected at their home. Analyses revealed no group differences in basal evening or morning cortisol levels; however, children with higher degrees of PCE exhibited blunted overnight increases in cortisol, controlling for additional risk factors. Race and caregiver depression were also associated with diurnal cortisol patterns. While repeated PCE may contribute to alterations in the normal or expected stress response later in life, sociodemographic and environmental factors are likewise important in understanding hormone physiology, especially as more time elapses from the PCE. Anticipating the potential long-term medical, developmental, or behavioral effects of an altered ability to mount a normal protective cortisol stress response is essential in optimizing the outcomes of children with PCE.
To determine if cynical hostility is associated with alterations in diurnal profiles of cortisol. Hostility has been linked to cardiovascular disease but the biological mechanisms mediating this association remain unknown.
Up to 18 measures of salivary cortisol taken over three days were obtained from each of 936 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Cynical hostility was measured using an 8-item subscale of the Cook-Medley Hostility scale. Cortisol profiles were modeled using regression spline models incorporating random parameters for subject-specific effects. Models were adjusted for race, sex, age, socioeconomic position, and lifestyle factors. The association of cynical hostility with key features of the cortisol diurnal profile, both in the full sample and important subsamples, was examined.
Waking cortisol levels as well as the extent of the morning surge in cortisol levels did not differ significantly across tertiles of cynical hostility. However respondents in the lowest tertile of cynical hostility experienced a 22% sharper decline in salivary cortisol (age-and sex-adjusted slope of −.49 μg/dl per hour) than respondents in the highest tertile (−.40 μg/dl per hour, p for difference=.0004). Intertertile differences in these parameters remained unaltered after further adjustment for potential confounders. This pattern of differences in cortisol diurnal profile tended to be related in a dose-response way to level of cynical hostility, and persisted in stratified analyses.
Cynical hostility is associated with the declining phase of the awakening cortisol response. The implications of this for cardiovascular and other health outcomes remain to be determined.
Cortisol rhythms; cynical hostility; regression splines; random effects; cortisol awakening response
Several studies show an association between exposure to aircraft or road traffic noise and cardiovascular effects, which may be mediated by a noise-induced release of stress hormones.
Our objective was to assess saliva cortisol concentration in relation to exposure to aircraft noise.
A multicenter cross-sectional study, HYENA (Hypertension and Exposure to Noise near Airports), comprising 4,861 persons was carried out in six European countries. In a subgroup of 439 study participants, selected to enhance the contrast in exposure to aircraft noise, saliva cortisol was assessed three times (morning, lunch, and evening) during 1 day.
We observed an elevation of 6.07 nmol/L [95% confidence interval (CI), 2.32–9.81 nmol/L] in morning saliva cortisol level in women exposed to aircraft noise at an average 24-hr sound level (LAeq,24h) > 60 dB, compared with women exposed to LAeq,24h ≤ 50 dB, corresponding to an increase of 34%. Employment status appeared to modify the response. We found no association between noise exposure and saliva cortisol levels in men.
Our results suggest that exposure to aircraft noise increases morning saliva cortisol levels in women, which could be of relevance for noise-related cardiovascular effects.
cardiovascular disease; gender differences
Objective: Morning cortisol levels are frequently used as screening tests for adrenal insufficiency in both adults and children. Reports differ on the specificity of this measurement. The present study was undertaken to determine whether sex or pubertal status affected morning cortisol values.
Methods: We measured morning cortisol levels and performed low-dose adrenocorticotropic hormone stimulation test in 35 healthy male and female subjects (ages 6-34) ranging in Tanner stage (TS) from TS 1 to TS 5. Testing was initiated at 08:00 after an overnight fast. Morning serum total cortisol, free cortisol, cortisol-binding globulin, estradiol (males and females), and testosterone (males) were obtained.
Results: Morning total and free cortisol levels were significantly higher in TS 5 participants than in prepubertal children. Using a morning cortisol of 248 nmol/L todefine a normal value, 19/21(90%) of healthy TS 5 subjects exhibit normal values. In contrast, 0/8 TS 1 healthy subjects exhibited a value greater than 248 nmol/L (p=0.0005). We also observed sex differences in morning cortisol levels in pubertal but not in prepubertal subjects. We observed sex differences in morning cortisol levels in TS 5 individuals.
Conclusions: Morning cortisol measurements may be more useful as screening tests for adrenal function in adults than in children. TS and sex may be considered in the decision to screen for adrenal insufficiency using morning cortisol or whether to proceed directly to stimulation testing.
Conflict of interest:None declared.
Morning cortisol; diurnal rhythm; adrenal insufficiency screening
Individuals differ widely in cortisol output over the day, but the etiology of these individual differences remains poorly understood. Twin studies are useful for quantifying genetic and environmental influences on variation in cortisol output, lending insight into underlying influences on the components of Hypothalamic-Pituitary-Adrenal (HPA) axis functioning.
Salivary cortisol was assayed on 446 twin pairs (157 monozygotic, 289 dizygotic; ages 7–8). Parents helped youth collect saliva 30 min after waking, mid-afternoon, and 30 minutes prior to bedtime across 3 consecutive days. We used hierarchical linear modeling to extract predicted cortisol levels and to distinguish cortisol’s diurnal rhythm using a slopes-as-outcome piecewise growth curve model; two slopes captured the morning-to-afternoon and afternoon-to-evening rhythm, respectively. Separate genetic models were then fit to cortisol level at waking, mid-afternoon, and evening as well as the diurnal rhythm across morning-to-afternoon and afternoon-to-evening hours.
Three results from these analyses are striking. First, morning-to-afternoon cortisol level showed the highest additive genetic variance (heritability), consistent with prior research. Second, cortisol’s diurnal rhythm had an additive genetic component, particularly across the morning-to-afternoon hours. In contrast, additive genetic variation did not significantly contribute to variation in afternoon-to-evening slope. Third, the majority of variance in cortisol concentration was associated with shared family environments. In summary, both genetic and environmental factors influence cortisol’s circadian rhythm, and they do so differentially across the day.
HPA axis; cortisol; diurnal rhythm; twins; behavior genetics
Elevated cortisol levels due to hypothalamic-pituitary-adrenal axis stress response have been associated with cognitive impairment. The causal relationship between stress and subsequent cognitive impairment remains, however, unclear notably due to small number of gender stratified prospective studies.
Salivary cortisol secretion was evaluated in 197 non-depressed community-dwelling elderly at three time points on the day of hospital attendance for a clinical examination and again on the following day at home, in distinct environment context. Cognitive performance was evaluated at baseline and 2- and 4-year follow-up.
Cross-sectional logistic analyses adjusted for age and education indicated that men with high morning cortisol at the hospital had higher risk of low cognitive performance in verbal fluency (OR=3.0, p=0.05) and visuo-spatial performance (OR=5.1, p=0.03). Impairment in verbal fluency was observed in women with moderate high morning cortisol (OR=3.6, p=0.05) or moderate slow diurnal rhythm (OR=3.7, p=0.04). In longitudinal analyses, slow diurnal rhythm (flatter slope) was associated with decline over 4 years in visuo-spatial performance (OR=7.7, p=0.03) and visual memory (OR=4.1, p=0.03) in men, and in verbal fluency (OR=6.0, p=0.01) in women. High morning cortisol was associated with decline in visual memory in women (OR=5.1, p=0.06).
Hypothalamic-pituitary-adrenal axis dysregulation appears associated with low cognitive performance in the elderly. Slower cortisol elimination rates could predict cognitive decline affecting principally non-verbal functioning in men and verbal functioning in women. The effects appeared independent of environmental context, apolipoprotein E genotype or psychopathology. Interventions blocking this pathway may provide new therapeutic options to prevent cognitive decline.
Cognition; cortisol; elderly; HPA axis; stress
A range of behavioral and psychosocial factors may contribute to a chronically stimulated hypo-thalamic-pituitary-adrenal (HPA) axis and subsequently altered diurnal patterns. The goal of this cross-sectional study was to examine associations among diurnal cortisol levels, perceived stress, and obesity patterns.
Seventy-eight women (aged 24–72 years) employed in a rural public school system completed the perceived stress scale, collected diurnal saliva samples, and underwent anthropometric assessments. Reduced peak-to-nadir cortisol values across the day were considered a sign of impairment in HPA function. A series of linear regression models determined the best predictors of diurnal cortisol variation.
There was a marginal linear trend in stress levels across body mass index (BMI) categories, with obese women reporting the highest levels of stress (p = 0.07). Perceived stress was the only significant predictor of the degree of flattening of the diurnal cortisol curve in the sample as a whole (β = −0.042, R2 = 0.11, F = 8.6, p = 0.005), indicating reduction in the normal diurnal pattern. Among overweight women (BMI = 25–29.9 kg/m2), stress and waist circumference combined predicted 35% of the variability in diurnal cortisol. In contrast, among obese women (BMI ≥ 30 kg/m2), BMI predicted 31% of the variability in diurnal cortisol (F = 13.8, p = 0.001), but stress was no longer significantly related to diurnal cortisol.
Psychological stress predicts a significant portion of HPA axis functioning. In overweight women, perceived stress and waist circumference were of approximately equal importance in predicting adrenal cortisol secretion. However, among obese women, a major portion of the diurnal cortisol variation was predicted by BMI alone, not stress or waist circumference. This may help elucidate the mechanisms linking obesity to increased risk of cardiovascular disease (CVD).
Objective The purpose of this study was to clarify the nature of diurnal salivary cortisol dysregulation in youth who experience posttraumatic stress (PTS). Method Diurnal trends in salivary cortisol secretion were examined in a sample of 41 youth aged 10–16 years (26 youth exposed to interpersonal traumas and 15 control participants with no PTS) using hierarchical linear modeling. Results Cortisol levels were characterized by curvilinear trends in secretion (i.e., sharp declines from prebreakfast to prelunch followed by smaller decreases from prelunch to predinner with a leveling-off or slight increase from predinner to prebed assessment). Results further indicated that youth with PTS had sharper morning declines and relatively higher evening levels (i.e., a greater curve in the daily trend) than nontraumatized youth. Conclusions Findings help to elucidate the physiological basis for altered arousal patterns in youth with PTS. Traumatized youth showed wider daily fluctuations in cortisol levels when these trends were modeled in a curvilinear fashion. The findings help to describe the nature of stress dysregulation in trauma-exposed youth and may have implications for clarifying some of the apparent inconsistencies in the literature.
cortisol; posttraumatic stress; hierarchical linear modeling
Elevated cortisol may be a risk factor for cognitive decline in aging. Genetic factors may influence individual vulnerability to the adverse effects of stress on cognitive function in aging.
We investigated whether gene-environment interaction by apolipoprotein E genotype and cortisol predicted cognitive performance in an urban population of older adults. A cross-sectional analysis of data was conducted from a population-based sample of 50–70 year old men and women. Cognitive performance, salivary cortisol levels, and APOE genotype was assessed in 967 subjects. Performance on 20 standard cognitive tests was assessed and combined to form seven summary domain scores (language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory and learning, visuoconstruction).
In adjusted models, while higher levels of cortisol were associated with worse cognitive scores, the slopes of the adverse relations were steeper in persons with at least one ε4 allele. Effect sizes were large: for example, the effect of having one ε4 allele and cortisol area under curve > 75th percentile was equivalent to a decrease in language score expected from an increase in 8.0 (95% CI: 1.7, 14.4) years of age, while having two ε4 alleles and cortisol area under curve > 75th percentile was equivalent to an increase of 33.4 (14.8, 52.0) years of age.
These data indicate that APOE genotype may modify relations of cortisol with cognitive functioning, and suggest that the ε4 allele increases vulnerability of the aging brain to the adverse effects of stress.
Serial saliva cortisol measurements were used to assess pituitary-adrenal function in a group of asthmatic children treated with beclomethasone dipropionate (400 micrograms daily). Asthmatic children who were not being treated with steroids and normal children were also studied for comparison. A diurnal cortisol rhythm was observed in all three groups. Early morning cortisol concentrations were significantly higher in the group treated with beclomethasone dipropionate than in the normal children; this may indicate a stress induced response to decreased morning peak expiratory flow. In both groups, plasma and salivary cortisol responses after adrenocorticotrophic hormone stimulation test were normal but peak cortisol concentrations showed a 7 fold increase over basal values in saliva compared with a three fold increase in plasma. Beclomethasone dipropionate does not suppress pituitary-adrenal function in children when used in recommended doses. Serial measurement of the salivary cortisol concentration is a simple, safe, and sensitive method for the routine monitoring of adrenal function in children treated with this steroid. Monitoring may be supplemented with an assessment of the adrenal response to adrenocorticotrophic hormone stimulation, if necessary.
Elevated morning cortisol is a prospective predictor of major depression and may serve as a vulnerability marker. We examined the relation between morning cortisol and two prominent risk factors for depression in preschool-aged children: maternal depression and child temperament. We also explored whether maternal depression during the child's life, parental hostility and life stress explained these associations.
94 children provided a morning salivary cortisol sample, and 92 children provided an evening sample. Child temperament and parenting were assessed using observational measures, and maternal depression and life stress were assessed with clinical interviews.
Maternal history of melancholic depression and child temperamental low positive emotionality were significantly associated with higher morning cortisol. These relations persisted after controlling for children's negative emotionality and concurrent depressive symptoms, parental hostility, and life stress.
Our findings support the hypothesis that elevated morning cortisol may serve as an early-emerging vulnerability factor for depression, and highlight the importance of anhedonia in risk for depression.
Depression risk; melancholia; HPA-axis; cortisol; temperament
We examined associations between cognitive function (CF) and the naturally occurring daily cortisol levels using data from the Midlife in the United States survey and the National Study of Daily Experiences.
A national sample of 1,500 (mean age = 57 years; range = 33–84, 56% female) completed a phone-based battery of cognitive tasks and 3–6 months later provided saliva samples upon waking, 30 min after waking, at lunch time, and at bedtime on 4 consecutive days.
Higher CF, particularly executive function, was associated with healthier daily cortisol profiles, including a steeper diurnal cortisol slope, higher morning cortisol levels, and lower afternoon and evening cortisol levels.
The results indicate that better CF is associated with healthier profiles of naturally occurring cortisol and underscore the importance of the timing of cortisol sampling.
Cognitive function; Diurnal cortisol rhythm; Salivary cortisol
Millions of adults in the United States travel abruptly across time zones each year. Nevertheless, the impact of traveling over relatively short distances (across 3 or fewer time zones) on diurnal patterning of typical physiological response patterns has yet to be studied in a large, epidemiological sample.
The current research focuses on 764 middle-aged men comparing variations in diurnal cortisol regulation based on number of time zones traveled eastward or westward the day before.
Main Outcome Measure
Participants provided samples of salivary cortisol at waking, 30-min postwaking, 10 a.m., 3 p.m., and bedtime.
Eastward travel was associated with a steeper salivary cortisol awakening response ( p < .01) and lower peak (PEAK) levels of salivary cortisol the next morning ( p < .05). Westward travel was associated with lower peak levels of cortisol the next morning ( p < .05). Effect sizes for these differences ranged from Cohen’s d = .29 to .47. Differences were not present for 2 days in their home environment.
The results provide evidence that traveling across time zones is associated with diurnal cortisol regulation and should be studied further to understand the subsequent impacts on health and well-being in large national samples.
jet lag; cortisol diumal rhythms; travel
Cortisol is a stress-related hormone with a robust circadian rhythm where levels typically peak in the morning hours and decline across the day. Although acute cortisol increases resulting from stressors are adaptive, chronic elevated cortisol levels are associated with poor functioning. Studies have shown age-related changes in cortisol levels. The present study investigated the relationship between salivary diurnal cortisol and functional outcomes among older adults undergoing inpatient post-acute rehabilitation.
Thirty-two older adults (mean age 78 years; 84% men) in a Veterans Administration inpatient post-acute rehabilitation unit were studied. Functional outcomes were assessed with the motor component of the Functional Independence Measure (mFIM; where mFIM change = discharge − admission score). Saliva samples were collected on 1 day at wake time, 45 minutes later, 11:30 AM, 2 PM, 4:30 PM, and bedtime. We analyzed the relationship between cortisol measures and functional outcomes, demographics, and health measures.
The analyses consistently showed that greater functional improvement (mFIM change) from admission to discharge was associated with lower comorbidity scores and higher cortisol levels at 2 PM, 4:30 PM, and bedtime. A morning cortisol rise was also associated with greater mFIM change.
Measurement of cortisol in saliva may be a useful biological marker for identification of patients who are “at risk” of lower benefits from inpatient rehabilitation services and who may require additional assistance or intervention during their post-acute care stay.
Cortisol; Older adults; Rehabilitation; Inpatient; Functional Status
Dysfunction of the hypothalamic-pituitary-adrenocortical axis (HPA-axis) is implicated in a variety of psychiatric and emotional disorders. In this study, we explore the association between HPA-axis functioning, as measured by morning cortisol, and common psychiatric disorders and symptoms among a community sample of adolescents.
Data from a cross-sectional school-based survey of 501 school pupils, aged 15, were used to establish the strength of association between salivary morning cortisol and both diagnosis of psychiatric disorders and a number of psychiatric symptoms, as measured via a computerised psychiatric interview. Analysis, conducted separately by gender, used multiple regressions, adjusting for relevant confounders.
With one exception (a positive association between conduct disorder symptoms and cortisol among females) there was no association between morning cortisol and psychiatric diagnosis or symptoms. However, there was a significant two-way interaction between gender and conduct symptoms, with females showing a positive and males a negative association between cortisol and conduct symptoms. A further three-way interaction showed that while the association between cortisol and conduct symptoms was negative among males with a few mood disorder symptoms, among females with many mood symptoms it was positive.
Except in relation to conduct symptoms, dysregulation of morning cortisol levels seems unrelated to any psychiatric disorder or symptoms. However, the relationship between cortisol and conduct symptoms is moderated by both gender and mood symptoms. Findings are compatible with the recent work suggesting research should concentrate on the moderated associations between gender, internalising and externalising symptoms and cortisol, rather than any simple relationship.
Morning cortisol; Stress; DSM-IV; Psychiatric diagnosis; Psychiatric symptoms; Adolescents