Diurnal Cortisol Rhythm Research Articles

Allostasis model facilitates understanding race differences in the diurnal cortisol rhythm

The concept of allostasis suggests that greater cumulative stress burden can influence stress-responsive physiology. Dysregulation of allostatic mediators, including the hypothalamic-pituitary-adrenal (HPA) axis, is thought to precede many other signs of age-related pathology as the persistent burden of stressors accumulates over the individual's life span. We predicted that even in young adulthood, HPA regulation would differ between Blacks and Whites, reflecting, in part, higher rates of stressor exposure and greater potential for stressors to "get under the skin." We examined whether stressor exposure, including experiences with racism and discrimination, explained race differences in waking cortisol and the diurnal rhythm. We also examined whether HPA functioning was associated with mental health outcomes previously linked to cortisol. Salivary cortisol was assayed in 275 young adults (127 Blacks, 148 Whites, 19 to 22 years old), four times a day across 3 days. Hierarchical linear models revealed flatter slopes for Blacks, reflecting significantly lower waking and higher bedtime cortisol levels compared to Whites. Associations of HPA functioning with stressors were typically more robust for Whites such that more stress exposure created an HPA profile that resembled that of Black young adults. For Blacks, greater stressor exposure did not further impact HPA functioning, or, when significant, was often associated with higher cortisol levels. Across both races, flatter slopes generally indicated greater HPA dysregulation and were associated with poor mental health outcomes. These differential effects were more robust for Whites. These findings support an allostatic model in which social contextual factors influence normal biorhythms, even as early as young adulthood.

To Nap or Not to Nap

Alterations in the sleep-wake cycle, including daytime napping, are consistently reported in persons with dementia (PWD). A dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis, indexed by elevated evening cortisol, may offer one explanation for these alterations. Alternatively, excessive daytime sleeping may alter cortisol rhythm and increase intraindividual variability, potentially contributing to increased environmental reactivity and behavioral symptoms. The purpose of this substudy (N = 12) was to examine the association between daytime napping and basal cortisol diurnal rhythm in nursing home residents with dementia. In this within-individual longitudinal design, saliva samples were obtained daily for 5 consecutive days upon waking and 30-45 min, 6 hr, and 12 hr after waking to obtain a cortisol diurnal rhythm. Behavior and sleep-wake state (nap/no nap) were observed and recorded every 20 min for 12 hr per day for 5 days. Participants were categorized as high nappers (HNs) or low nappers (LNs). There was a significant difference in evening cortisol levels (t = -2.38, p = .032) and continence (t = 3.37, p = .007) between groups, with HNs exhibiting higher evening cortisol levels. There were no other significant differences in resident characteristics between the two groups. These data suggest a link between excessive daytime napping and elevated evening cortisol in PWD consistent with findings in children. Elevated evening cortisol is an indication of a dysregulation in the HPA axis. These preliminary data support a close association between the sleep-wake cycle and HPA-axis regulation in PWD.

Cortisol Diurnal Rhythm and Stress Reactivity in Constipation and Abdominal Pain

The aim of this study was to assess whether diurnal cortisol rhythm and cortisol stress reactivity were associated with functional constipation and abdominal pain in infancy. This study was embedded in a subset of the Generation R Study, a prospective cohort study from fetal life onward in Rotterdam, the Netherlands. Data of infants between 14 and 24 months of age (N =483) were used. Salivary cortisol diurnal rhythm and salivary cortisol stress reactivity after a Strange Situation Procedure were assessed at age 14 months. Data on functional constipation were available according to the Rome II criteria, and data on abdominal pain on the basis of the Abdominal Pain Index were available from questionnaire data at 24 months. In the second year of life, 13% of the infants had functional constipation and 17% had abdominal pain. Only 4% had symptoms of both functional constipation and abdominal pain. Diurnal cortisol rhythm did not differ significantly between children with and children without functional constipation and abdominal pain. Cortisol stress reactivity was slightly higher in infants with abdominal pain than in those without it, but this was not statistically significant (odds ratio 1.41; 95% confidence interval 0.46-4.31). No association was found between the cortisol stress reactivity and functional constipation. Our results suggest that cortisol as a marker for stress does not play a major role in functional constipation or abdominal pain in infancy.

Salivary cortisol in pregnant women suffering from blood and injection phobia

Stress and/or anxiety during pregnancy affect maternal and fetal well-being and can cause premature delivery and postnatal pathology in the child. Women suffering from phobias related to blood and injections are prone to high levels of stress, including anxiety and sometimes panic attacks, during pregnancy. Cortisol is amongst the mediators through which the neurohormonal expressions of maternal psychological factors may be transduced to the fetus. The aim of this study was to investigate whether pregnant women suffering from blood and injection phobia have raised cortisol levels or are characterized by unusual diurnal salivary cortisol profiles compared with healthy controls. The sample consisted of 110 pregnant women with blood and injection phobia and 110 pregnant healthy controls. Both groups provided morning and evening saliva samples in weeks25 and 36 for the assay of cortisol. In gestational week25, when blood was drawn for the mandatory blood testing, extra blood was taken to analyze corticotrophin-releasing factor, adrenocorticotropic hormone, and cortisol in serum. The diurnal decline in salivary cortisol as well as increased cortisol levels were observed during pregnancy. Pregnant women suffering from blood and injection phobia had a higher output of cortisol compared with women without the phobia (F = 6.25, df = 1, p = 0.014), but no marked difference in the diurnal cortisol rhythm was found between groups. Our findings indicate that untreated blood and injection phobia during pregnancy increases cortisol concentrations. Blood and injection phobia is treatable, and cognitive behavioral therapy can be used. Women with blood and injection phobia during pregnancy therefore need to be recognized and offered treatment without delay in early pregnancy.

113. Daily stressors and marital interactions affect diurnal cortisol and alpha-amylase rhythm in spouses of persons with mild cognitive impairment

113. Daily stressors and marital interactions affect diurnal cortisol and alpha-amylase rhythm in spouses of persons with mild cognitive impairment

Ageing, physical function, and the diurnal rhythms of cortisol and dehydroepiandrosterone

The present study examined the relationship between ageing, physical function and the diurnal rhythms of cortisol and dehydroepiandrosterone (DHEA). Participants were 36 community dwelling older adults aged between 65 and 86 years old. Salivary cortisol and DHEA were measured over the course of one day: immediately upon awakening, 30 min later, and then 3 h, 6 h, 9 h and 12 h post-awakening. Participants completed the Nottingham extended activities of daily living index, the Berg Balance Scale and their handgrip strength was assessed. Older participants had a significantly higher cortisol area under the curve (AUC), lower overall DHEA levels, lower DHEA AUC, a decreased diurnal slope of decline and increased cortisol:DHEA ratio. Lower diurnal cortisol levels were associated with poorer performance on the Berg Balance Scale and lower handgrip strength, and those with a flattened DHEA diurnal profile reported less independence in carrying out daily tasks. These associations withstood adjustment for age. In conclusion, this study suggests an association between cortisol, DHEA, ageing and physical function.

Symptoms of attention deficit hyperactivity disorder in children are associated with cortisol responses to psychosocial stress but not with daily cortisol levels

We tested associations of diurnal hypothalamic-pituitary adrenal axis (HPAA) activity and its response to stress with behavioral symptoms of Attention Deficit Hyperactivity Disorder (ADHD) among 272 eight-year-old children. We measured their diurnal salivary cortisol and salivary cortisol responses to the Trier Social Stress Test for Children (TSST-C). Mothers rated their child’s behavior with the ADHD-IV Rating Scale and the Child Behavior Checklist (CBCL). There were no significant associations between ADHD symptoms and diurnal cortisol concentrations. The boys with predominantly inattentive symptoms of ADHD (ADHD-I; scores at or above the 90th percentile) had 26% lower mean salivary cortisol levels during the TSST-C than the boys with scores below this cutoff. In the girls with symptoms of ADHD-I, initial salivary cortisol levels prior to the TSST-C were higher and fell more rapidly during and after the TSST-C, which was not seen in the remaining girls ( P = 0.007 for interaction ‘ADHD-I × sampling time’). Controlling for Oppositional Defiant Disorder/Conduct Disorder and Anxiety Disorder or excluding children with these comorbid problems did not substantially affect these findings. We conclude that the boys and the girls with behavioral symptoms of ADHD-I had reduced HPAA responsiveness to stress, which is also seen in people after traumatic events or with chronic stress. Their diurnal cortisol rhythm was not affected. Thus, ADHD-I may be associated with dysregulation of the HPAA or reduced engagement with stressful stimuli.

Growth delay as an index of allostatic load in young children: Predictions to disinhibited social approach and diurnal cortisol activity

The goal of this study was to examine whether growth delay can serve as an index of allostatic load during early development, as it is well known that the activity of stress-mediating systems inhibits growth. The participants were children adopted internationally from institutional care (n = 36), children adopted internationally from foster care (n = 26), and nonadopted children (n = 35). For the adopted children, height for age and weight for height were assessed at adoption; for all children, disinhibited social approach (DSA; termed elsewhere as "indiscriminate friendliness") and diurnal cortisol were assessed at 6-8 years (M = 6.9 years). For internationally adopted children in general, and postinstitutionalized children specifically, linear growth delay assessed at the time of adoption was associated with more dysregulated behavior in response to an unfamiliar adult (i.e., greater DSA) and a more dysregulated diurnal cortisol rhythm (i.e., higher late afternoon and evening values). Further, among the most growth-delayed children, higher cortisol levels later in the day were correlated with DSA. The potential for using growth delay as an allostatic load indicator and the possible problems and limitations in its use in child populations are discussed.

Effects of Daily Stressors on the Psychological and Biological Well-being of Spouses of Persons With Mild Cognitive Impairment

This research documents spousal accounts of daily symptoms and behaviors of their husbands or wives with mild cognitive impairment (MCI) and assesses how MCI-related symptoms and care needs are associated with spouse care partners' psychological well-being and biomarkers of physiological wear and tear. Thirty spouse care partners participated in a 7-day diary study and reported on behavior problems associated with MCI as well as daily stressors and strains they experienced. They also provided saliva samples on 4 of the study days. Multilevel models revealed daily variability and change in psychological affect and the diurnal cortisol rhythm. Daily primary stressors, everyday secondary strains, and marital interactions predicted these changes. The findings document the negative physiological effects of having a spouse with MCI and provide new details on probable causes of psychological and biological distress. They shed light on MCI-specific interventions to address couples' needs before severe disease progression occurs that could interfere with spouses' ability to provide home-based care and support.

Diurnal cortisol rhythms in Tsimane’ Amazonian foragers: New insights into ecological HPA axis research

Although a growing body of research has documented important pathways by which the HPA axis mediates the interface between the psychosocial world and individual health, there is a paucity of data from nonwestern populations, particularly from those populations with distinct nutritional and infectious disease ecologies. The specific objectives of this study are: (1) to document variation in diurnal cortisol rhythms among the Tsimane', a remote population in the Bolivian Amazon, (2) to explore this variation by age and by gender, and (3) to compare diurnal rhythms from this study to other population based studies of cortisol conducted in industrialized nations. Salivary cortisol samples were collected twice daily, immediately upon waking and before bed, for three consecutive days from 303 participants (age 1.6-82 years, 1564 samples) in conjunction with the Tsimane' Amazonian Panel Study (TAPS). Cortisol rhythms showed strong age effects across the developmental span, with basal levels and slopes increasing into adulthood, although individuals older than 60 years demonstrated a precipitous flattening of the diurnal slope. Cortisol profiles were elevated in adult females compared to their age-matched male counterparts, and diurnal slopes, as well as mean cortisol concentrations among the Tsimane' were the lowest reported in any population based study of HPA axis function. Although the within-population variation in cortisol profiles was consistent with the established correlates of time of day, age, and sex, the between-population comparisons revealed dramatically lower levels of HPA activity among the Tsimane'. This study provides a benchmark against which to reference cortisol levels from industrialized populations, and expands the range of documented variation in HPA axis function in a nonwestern context.

Differential effects of perceived discrimination on the diurnal cortisol rhythm of African Americans and Whites

The current study considered the influence of perceived discrimination on the diurnal cortisol rhythm of 50 African American older adults and a matched comparison groups of 100 Whites (M(age)=56.6; 58% female). The role of socioeconomic status (SES) as a moderator of the effects of discrimination on the diurnal decline was also considered for each group. In support of the idea that perceptions of unfair treatment take on a unique meaning for stigmatized minority groups, results suggest that perceived discrimination is associated with a flatter (less healthy) diurnal slope among Whites but a steeper (more healthy) diurnal slope among African Americans. Perceived discrimination was also found to be more strongly associated with a steepening of the diurnal slope among lower SES African Americans than higher SES African Americans.

Negative emotionality, depressive symptoms and cortisol diurnal rhythms: Analysis of a community sample of middle-aged males

Prior research suggests that individuals with particular personality traits, like negative emotionality, are at greater risk for adverse health outcomes. Despite bivariate associations between negative emotionality, depressive symptoms and the hypothalamic pituitary adrenal axis (HPA axis), few studies have sought to understand the biological pathways through which negative emotionality, depressive symptomatology and cortisol—one of the primary hormonal products of the HPA axis—are associated. The present study explored whether negative emotionality influenced cortisol dysregulation through current depressive symptomatology and whether negative emotionality served as a moderator of the relationship between depressive symptoms and cortisol. In the community-based Vietnam Era Twin Study of Aging, 783 male twins completed two days of cortisol saliva sampling in their natural environments. Three measures of cortisol were analyzed: waking levels, the cortisol awakening response, and the peak to bed slope. Depressive symptoms significantly mediated the associations between negative emotionality and the peak to bed slope. A 2-way interaction between depressive symptoms and negative emotionality was significant for the peak to bed slope and for waking levels of cortisol. Exploration of the interactions illustrated that depressive symptoms only affected cortisol slopes at average or high levels of negative emotionality and only affected waking levels at low levels of negative emotionality. Negative emotionality and depressive symptoms were not related to the cortisol awakening response. This is the first study to find indirect associations between negative emotionality and peak to bed cortisol slopes through depressive symptoms. These findings illustrate the complex interplay between personality characteristics, depressive symptoms and different indices of the cortisol diurnal rhythm.

FC14-02 - Biological stress markers, executive functions and self-perceived stress in adults with ADHD (attention-deficit /hyperactivity disorder)

IntroductionThe management of normal daily tasks may be complicated for adults with ADHD (attention-deficit/hyperactivity disorder) due to executive dysfunctions. ADHD may thus increase the risk of chronic stress in everyday life.ObjectiveTo study endocrinological and psycho physiological stress markers in adults with ADHD in association to performance in test of executive functions (EF) and self-perceived stress.MethodsCardiovascular stress markers were assessed in 30 adults with ADHD with no psychoactive medication, and 30 healthy controls during: (1) non-stress baseline; (2) cognitive stress; and (3) non-stress recovery. The Visual Analogues Scale was used to assess self-perceived stress. Salivary cortisol was measured pre- and post-experiment. To measure stress in everyday life we assessed diurnal cortisol values, stressors and self-ratings of stress.ResultsThe group with ADHD showed higher self-perceived stress but attenuated or atypical cardiovascular stress reactivity during experimentally induced stress, and stress reactivity predicted performance in the executive test. Baseline cardiovasular values did not differ from the controls. The diagnosis of ADHD significantly increased the risk of belonging to the group with high post-stress cortisol levels. The two groups were comparable with respect to overall diurnal cortisol levels and rhythm. The ADHD group reported significantly higher self-perceived stress and these values correlated with level of stressors in everyday life.ConclusionsThe overall baseline values in biological stress markers may be comparable between adults with ADHD and healthy controls, while the stress reactivity and recovery pattern may differ between the two groups.

Diurnal variation of cortisol in people with dementia: relationship to cognition and illness burden.

Cortisol patterns in nursing home residents with dementia are described and examined in relation to cognition and comorbid illnesses. Saliva was sampled 4 times in a 24-hour period (week 1) and at the same times 1 week later (week 2). In general, cortisol levels decreased from morning to evening, with 50% exhibiting a negative slope. In contrast, 38% of the participants had a relatively flat cortisol diurnal rhythm, and 7% exhibited an afternoon increase. The cortisol pattern was consistent between weeks 1 and 2 for 39% with a negative slope, 13% with a flat profile, and for 2% with an afternoon increase pattern. Cortisol rhythm was not statistically significantly related to cognition or illness burden. While this study contributes to the understanding of differences in the diurnal pattern of cortisol for older adults with dementia, more research is needed to understand the etiology of the differences and the biological mechanisms involved.

Transient Efficacy of Octreotide and Pasireotide (SOM230) Treatment in GIP-dependent Cushing's Syndrome

We studied a 55-year old woman presenting with features of Cushing's syndrome associated with metabolic abnormalities including severe hypertension and type 2 diabetes. Urinary free cortisol excretion was within normal limits, but an unusual diurnal cortisol rhythm was observed with low morning and high postprandial levels, associated with the absence of cortisol suppression after dexamethasone, suggesting the possibility of GIP-dependent Cushing's syndrome. The diagnosis was confirmed by further investigations, showing significant plasma cortisol responses after a mixed meal test and after oral, but not intravenous glucose administration, as well as ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH). An aberrant increase in cortisol was also observed after glucagon and terlipressin injections. The patient was first treated with octreotide 100-250 μg thrice daily for 6 months, then with the new multi-ligand somatostatin analogue (SOM 230) 450-900 μg twice daily for 3 months. Although inducing a significant acute suppression of post-prandial cortisol response, both drugs had no effects on the clinical and metabolic abnormalities associated with Cushing's syndrome and new tests performed at the end of each treatment period confirmed escape of post-meal cortisol suppression to therapy. The patient finally underwent a bilateral adrenalectomy, which markedly improved her medical condition and allowed in vitro confirmation by real time RT-PCR quantification of a high aberrant expression of GIP receptor mRNA in adrenal tissue. This case report illustrates the lack of sustained efficacy of somatostatin analogues on GIP-dependent Cushing's syndrome, independent of their affinity for the different somatostatin receptor subtypes.

Spousal loss predicts alterations in diurnal cortisol activity through prospective changes in positive emotion.

The objective of this study was to examine the role of spousal bereavement and positive emotion in naturally occurring levels of daily cortisol. Analyses were conducted using data from the Midlife in the United States survey and the National Study of Daily Experiences. Baseline assessments of extraversion, neuroticism, trait positive emotion, and trait negative emotion were obtained, as were reports of demographic and health behavior covariates. Salivary cortisol levels were measured at wakeup, 30 min after awakening, before lunch, and at bedtime on each of 4 successive days. Multilevel growth curve analyses indicated that independent of age, gender, education, extraversion, neuroticism, negative emotion, medication use, and smoking, spousal bereavement was associated with lower levels of cortisol at wakeup and a flattening of the diurnal cortisol rhythm. Mediation analyses revealed that prospective changes in positive emotion accounted for the impact of bereavement on diurnal cortisol slopes. The current prospective study is among the first to provide evidence for a role for positive emotion as a mechanism by which bereavement influences hypothalamic-pituitary-adrenal axis dysregulation in older adults.

Reciprocal Relations Between Objectively Measured Sleep Patterns and Diurnal Cortisol Rhythms in Late Adolescence

To examine how hours of sleep and wake times relate to between-person differences and day-to-day changes in diurnal cortisol rhythms in late adolescence. Older adolescents (N = 119) provided six cortisol samples (wakeup, +30 minutes, +2 hours, +8 hours, +12 hours, and bedtime) on each of three consecutive days while wearing an actigraph. We examined how average (across 3 days) and day-to-day changes in hours of sleep and wake times related to diurnal cortisol patterns. On average, more hours of sleep related to steeper decline in cortisol across the days. Day-to-day analyses revealed that the hours of sleep of the previous night predicted steeper diurnal slopes the next day, whereas greater waking cortisol levels and steeper slopes predicted more hours of sleep and a later wake time the next day. Our results suggest a bidirectional relationship between sleep and hypothalamic-pituitary-adrenal axis activity.

Abolished circadian rhythm of salivary cortisol in elite artistic gymnasts

Objective The aim of this study was to evaluate the effects of intensive physical exercise and acute psychological stress during high level athletic competition as reflected on the levels of salivary cortisol in elite artistic gymnasts (AGs). Design The study included 239 AGs (142 females–97 males) who participated in the European Championship of Gymnastics in 2006 and 81 adolescents (40 females–41 males), matched for age, as controls. All athletes participated voluntarily in all or parts of the study, providing samples or data for each of the variables measured. Height, weight, body fat, lean body mass (LBM), bone age and Tanner stage of puberty were assessed and data concerning the time of thelarche, adrenarche and menarche as well as, the onset and the intensity (hours per week) of training were obtained. Methods Saliva samples were collected, the morning before training and in the afternoon shortly after the competition. From controls, the saliva samples were collected in the morning. Cortisol concentrations were measured using a chemiluminescence method. Acute stress was assessed using a questionnaire designed for the study. Results No difference was found between morning and afternoon salivary cortisol levels in both male and female AGs (females: AM: 15.45 ± 7.45 nmol/l vs PM: 15.73 ± 9.38 nmol/l; males: AM: 10.21 ± 5.52 nmol/l vs PM: 9.93 ± 13.8 nmol/l, p > 0.05). Female AGs presented higher levels of morning salivary cortisol than female controls ( p < 0.05). Both male and female AGs had higher degree of psychological stress in comparison with controls ( p < 0.001, p < 0.013, respectively). Female AGs had higher morning and afternoon salivary cortisol levels ( p < 0.01, p < 0.01, respectively) and higher degree of stress ( p < 0.003) than males. Conclusions In elite AGs the diurnal rhythm of salivary cortisol has been abolished, probably due to the strenuous training and competition conditions. Female AGs presented higher levels of morning salivary cortisol and psychological stress compared to both male AGs and female controls. The long term consequences of these modifications of the HPA axis remain to be elucidated.

Disentangling psychobiological mechanisms underlying internalizing and externalizing behaviors in youth: Longitudinal and concurrent associations with cortisol

Research examining cortisol dysregulation is seemingly contradictory with studies showing that both internalizing and externalizing behaviors are related to high and low cortisol. One extant theory to explain divergent findings in the stress literature is that both hypo- and hyper-arousal of the hypothalamic–pituitary–adrenal (HPA) axis may be present depending on time since onset of the stressor. This theory may extend to the onset of internalizing and externalizing behaviors. Data from 96 youth participating in a longitudinal project were used to examine this possibility. Composite measures of internalizing and externalizing behaviors at both childhood and early adolescence were formed using mother and teacher reports. Multiple salivary cortisol samples were also collected over two consecutive days during early adolescence. Problematic behaviors were associated with cortisol and the direction of the association was dependent on amount of time passed since onset of the behaviors. When examined concurrently in adolescence, youth with more internalizing behaviors had higher morning cortisol; however, when examined longitudinally, youth with more internalizing behaviors in childhood had lower morning cortisol levels as adolescents. Youth with more externalizing behaviors in childhood had flattened diurnal cortisol rhythms as adolescents, and this finding persisted when examined in adolescence. Cortisol dysregulation was greatest in children with the most severe behavior problems. Findings support the theoretical model of blunting of the HPA axis over time. While the HPA axis may show hyper-arousal when youth first display behaviors, long-term exposure may lead to a hypo-arousal of the HPA axis which culminates in a dysregulated diurnal rhythm.

Abnormal diurnal pattern of cortisol secretion in patients after aneurysmal subarachnoid hemorrhage

Substantial evidence suggests that impairment of the hypothalamus–pituitary system can occur following an aneurysmal subarachnoid hemorrhage (aSAH). Given that the diurnal cortisol rhythm is primarily controlled by the hypothalamus–pituitary system, this study examined whether changes in diurnal cortisol rhythm occurred after aSAH. Cortisol concentrations were measured in the saliva samples collected from patients after aSAH and other types of cerebral hemorrhage (non-aSAH) in the post-awakening period and at night (21:00 h), and the cortisol awakening response (CAR) and diurnal cortisol decline were determined. The area under the cortisol curve from immediately after to 45 min after awakening (CARauc) in the aSAH patient group was comparable to that in the non-aSAH or healthy control groups. However, an obvious cortisol peak was not found after the awakening period, and the morning/nighttime cortisol ratio in the aSAH patient group was significantly lower than that in other examined groups due to higher nighttime cortisol concentrations. In aSAH patients, the CARauc and nighttime cortisol concentrations were negatively correlated with the Fisher CT grade. These results indicate that the diurnal cortisol rhythm is not regulated normally after aSAH, and cortisol secretory activity decreases as the volume of subarachnoid bleeding increases. Our findings will be helpful to understand altered hypothalamus–pituitary–adrenal axis function after aSAH.