Diurnal rhythms in plasma cortisol, insulin, glucose, lactate and urea in pigs fed identical meals at 12-hourly intervals

Diurnal rhythms in plasma cortisol, insulin, glucose, lactate and urea concentrations were investigated in eight catheterized pigs of approximately 35 kg BW. Pigs were fed isoenergetic/isoproteinic diets at a restricted level (2.5 x maintenance requirement for energy) in two daily rations (06:00 and 18:00 hours) in order to obtain equal intervals between feed intake. Preprandial plasma cortisol concentration was 22+/-3 ng/mL in the morning and 14+/-2 ng/mL in the evening (p<0.025), whereas the concentrations of insulin, glucose, lactate, and urea were similar. In the postprandial period in the morning (06:00-09:00 hours) plasma cortisol, insulin and lactate concentrations (expressed as the total area under the curve) were greater (p<0.001) compared to the evening (18:00-21:00 hours) by 100%, 42%, and 24%, respectively, while postprandial plasma glucose and urea concentrations were not affected by time of the meal. When postprandial plasma concentrations were expressed as a response over preprandial concentrations (decremental or incremental area under the curve), the diurnal rhythm was not observed for cortisol and glucose, persisted for insulin and lactate, and appeared for urea with a smaller postprandial urea response (p<0.05) in the morning compared to the evening. We conclude that the diurnal rhythm in plasma cortisol is independent of feeding whereas the diurnal rhythms in plasma insulin, lactate and urea are unveiled by the morning/evening meals in pigs. At equal 12-h intervals between meals, the postprandial responses of lactate and urea show diurnal variations, each in a specific manner, which suggest decreased postprandial efficiency of carbohydrate metabolism and increased postprandial efficiency of protein metabolism in the morning compared to the evening.     

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.     

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.     

Chronotype and diurnal patterns of positive affect and affective neural circuitry in primary insomnia

While insomnia is a well-established risk factor for the initial onset, recurrence or relapse of affective disorders, the specific characteristics of insomnia that confer risk remain unclear. Patients with insomnia with an evening chronotype may be one particularly high-risk group, perhaps due to alterations in positive affect and its related affective circuitry. We explored this possibility by comparing diurnal patterns of positive affect and the activity of positive affect-related brain regions in morning- and evening-types with insomnia. We assessed diurnal variation in brain activity via the relative regional cerebral metabolic rate of glucose uptake by using [(18) F]fluorodeoxyglucose-positron emission tomography during morning and evening wakefulness. We focused on regions in the medial prefrontal cortex and striatum, which have been consistently linked with positive affect and reward processing. As predicted, chronotypes differed in their daily patterns in both self-reported positive affect and associated brain regions. Evening-types displayed diurnal patterns of positive affect characterized by phase delay and smaller amplitude compared with those of morning-types with insomnia. In parallel, evening-types showed a reduced degree of diurnal variation in the metabolism of both the medial prefrontal cortex and the striatum, as well as lower overall metabolism in these regions across both morning and evening wakefulness. Taken together, these preliminary findings suggest that alterations in the diurnal activity of positive affect-related neural structures may underlie differences in the phase and amplitude of self-reported positive affect between morning and evening chronotypes, and may constitute one mechanism for increased risk of mood disorders among evening-type insomniacs.     

Interindividual Differences in Diurnal Variations in Alertness,Performance, and Adrenaline Excretion

Pátkai , P. Interindividual differences in diurnal variations in alertness, performance, and adrenaline excretion. Acta physiol. scand. 1971. 81. 35–46. Subjects classified as habitual morning vs. evening workers on the basis of their answers to a questionnaire, were compared with regard to day-time variations in catecholamine excretion and performance. Adrenaline excretion in morning workers was highest in the morning and decreased gradually during the day, while evening workers showed nearly constant excretion values. The performance of morning workers did not vary during the day, while evening workers showed a steady improvement, performing best in the evening. In addition, a significant difference between the two groups was found in the personality dimension of extraversion-introversion, showing that evening workers were more extravert and morning workers more introvert. The constancy of individual diurnal rhythms and their relations to personality traits, are discussed.     

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.     

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

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

Diurnal and ultradian variations of plasma concentrations of eleven adrenal steroid hormones in human males

Summary The diurnal variations of the plasma concentrations of eleven steroid hormones and of corticotropin (ACTH) were studied in ten young healthy males. The plasma steroids progesterone, pregnenolone, deoxycorticosterone, 17-OH-progesterone, 17-OH-pregnenolone, deoxycortisol, 18-OH-deoxycorticosterone, corticosterone, aldosterone, cortisol and 18-OH-corticosterone, as well as plasma ACTH, were measured at 30-min intervals in the morning and in the evening and at 2-h intervals during the rest of the day.Steroids were extracted from 1 ml plasma, fractionated by high-pressure liquid chromatography (HPLC) and finally quantified by radioimmunoassay (RIA). Plasma concentrations of ACTH were radioimmunoassayed after extraction from 2 ml plasma.More or less pronounced circadian and episodic variations were apparent for plasma levels of all steroids studied, as well as of ACTH. According to related profiles of diurnal variations of plasma concentrations, three different categories of steroids were tentatively crystallized. Category 1 includes 17-OH-pregnenolone, deoxycortisol, corticosterone, 18-OH-deoxycorticosterone, deoxycorticosterone, cortisol and 18-OH-corticosterone, exhibiting a rhythm partly synchronous with that of the pituitary secretory activity of ACTH. Category 2, including progesterone, pregnenolone and 17-OH-progesterone, exhibited a time course of plasma concentrations assuming a regulation predominantly dictated by the testicular secretory activity. Lastly, aldosterone exerted a variation of plasma concentrations which was obviously regulated by the renin-angiotensin system under the present conditions.The paper was presented in part to the Joint Congress of the Scandinavian and German Societies of Clinical Chemistry, Hamburg 8. — 11.10.1980     

Cortisol and somatization

Somatization symptoms are frequently associated with depression, anxiety, and feelings of distress. These features interact with the activity of the HPA-axis. Therefore we investigated relationships between somatization symptoms and cortisol. Seventy-seven participants were classified into three groups: somatization syndrome (at least eight physical symptoms from the DSM-IV somatization disorder list), somatization syndrome combined with major depression, and healthy controls. The following data were collected: salivary cortisol at three time points (morning, afternoon, evening), nighttime urinary cortisol, serum cortisol after the dexamethasone suppression test (DST), and psychological variables such as depression, anxiety, somatization, and hypochondriasis. Salivary cortisol showed typical diurnal variations. However, the groups did not differ on any of the cortisol variables. A possible explanation may be counteracting effects of somatization and depression. Exploratory correlational analyses revealed that associations between cortisol and psychopathological variables were time-dependent. DST results correlated with psychological aspects of somatization, but not with the number of somatoform symptoms per se.     

Diurnal courses of cortisol, pain, fatigue, negative mood, and stiffness in patients with recently diagnosed rheumatoid arthritis

To investigate the diurnal courses of cortisol and the daytime states: pain, fatigue, negative mood, and stiffness of patients with rheumatoid arthritis, as well as the association between the cortisol and state courses, 9 repeated measurementson 2consecutive days were taken in the real-life environment of 25 recently diagnosed patients (19 women, 6 men; mean age 55.2 years) and 28 healthy controls (20 women, 8 men; mean age 55.8 years). Patients showed a highly characteristic diurnal course of cortisol (F_{8, 15} = 7.4, p < .001) and a significant diurnal fatigue (F_{7, 18} = 2.6, p < .05) and early morning stiffness course (F3, 22 = 6.2, p < .01), but the temporal association between these courses was low. Daytime states, notably fatigue (r = 0.40, p < .05), were positively correlated with the early morning rise of cortisol and nighttime pain (r ≥ 0.53, p < .01) but not with cortisol level or inflammatory activity. Cortisol level and inflammatory activity were positively correlated (r = 0.47, p < .05). These results suggest that in patients with rheumatoid arthritis, cortisol has a strong endogenous rhythm that is not disturbed by inflammatory activity. It appears that diurnal fluctuations in fatigue and stiffness are independent of the circadian rhythm of cortisol or inflammatory activity, but rather reflect temporal changes as a consequence of sleep, rest, and physical activity throughout the day.     

Diurnal fluctuation of time perception under 30-h sustained wakefulness

Previous studies have reported that time perception in humans fluctuates over a 24-h period. Behavioral changes seem to affect human time perception, so that the fluctuation in human time perception may be the result of such changes due to self-determined activities. Recently, we carried out a study in which a healthy human cohort was asked to perform simultaneously loaded cognitive tasks under controlled conditions, and found that time perception decreased linearly from morning to evening. In addition, the variations in time perception were not a consequence of behavioral changes. It remains to be elucidated whether diurnal variations in time perception are a consequence of circadian rhythm or of some homeostatic changes that are attributable to accumulated wake time. The effects of circadian rhythm on time perception were investigated in eight healthy young male volunteers by conducting 10-s time production tasks under 30-h constant-routine conditions. Core body temperature and serum melatonin and cortisol levels were measured during the course of the study. Produced time exhibited a diurnal variation and was strongly correlated with circadian variations in core body temperature and serum melatonin levels. These results suggest that human short-term time perception is under the influence of the circadian pacemaker.     

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     

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.     

Diurnal saliva cortisol levels and relations to psychosocial factors in a population sample of middle-aged swedish men and women

Whereas psychosocial risk factors increase the risk for disease, psychosocial resources reduce this risk. To examine a possible pathway for these effects, the relations between saliva cortisol levels and psychosocial factors were studied in a random sample of 257 men and women aged 30 to 64 years. Saliva samples were collected at home on waking, 30 min after waking, and in the evening. A flatter diurnal rhythm of cortisol, that is, lower deviations between awakening and evening cortisol levels, was related to high levels of psychosocial risk factors (cynicism, depression, and vital exhaustion), whereas a steeper diurnal rhythm was related to psychosocial resources (social support and coping), general health, and well-being (all p < .05). Our results support earlier suggestions that the capacity of the hypothalamic-pituitary-adrenal-axis to dynamically respond to stress is 1 pathway for observed effects of psychosocial factors regarding risk for disease development.     

The 3111 Clock gene polymorphism is not associated with sleep and circadian rhythmicity in phenotypically characterized human subjects

Mutations in clock genes are associated with abnormal circadian parameters, including sleep. An association has been reported previously between a polymorphism (3111C), situated in the 3'-untranslated region (3'-UTR) of the circadian gene Clock and evening preference. In the present study, this polymorphism was assessed in: (1) 105 control subjects with defined diurnal preference, (2) 26 blind subjects with free-running circadian rhythms and characterized with regard to circadian period (tau) and (3) 16 delayed sleep phase syndrome patients. The control group was chosen from a larger population (n = 484) by Horne-Ostberg questionnaire analysis, from which three subgroups were selected (evening, intermediate and morning preference). Data from sleep diaries completed by 90% of these subjects showed a strong correlation between preferred and estimated timings of sleep and wake. The mean timings of activities for the evening group were at least 2 h later than the morning group. Genetic analysis showed that, in contrast with the previously published finding, there was no association between 3111C and eveningness. Neither was there an association between 3111C and tau, nor a significant difference in 3111C frequency between the normal and delayed sleep phase syndrome groups. To assess the effect of this polymorphism on messenger RNA (mRNA) translatability, luciferase reporter gene constructs containing the two Clock polymorphic variants in their 3'-UTR were transfected into COS-1 cells and luciferase activity measured. No significant difference was observed between the two variants. These results do not support Clock 3111C as a marker for diurnal preference, tau, or delayed sleep phase syndrome in humans.     

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 weeks 25 and 36 for the assay of cortisol. In gestational week 25, 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.     

Maternal Sleep Quality and Diurnal Cortisol Regulation Over Pregnancy

Poor sleep in pregnancy is related to adverse neonatal health. Elevated maternal cortisol has been proposed as a pathway, yet the association in pregnancy is not well understood. The goals of the current study were to examine associations between (a) sleep and cortisol, (b) sleep, cortisol, and neonatal outcomes, and (c) variables that could explain these associations. Two hundred pregnant women completed the Pittsburgh Sleep Quality Index (PSQI; Buysse, Reynolds, Monk, Berman, & Kupfer, 1989) and provided diurnal salivary cortisol samples at two times over pregnancy. Poor sleep quality was associated with greater evening cortisol concentrations at 36 weeks’ gestation. This association was mediated by anxiety symptoms. Higher evening cortisol at 36 weeks’ gestation was associated with shorter gestation.     

Adrenocortical activity in at-risk and normally developing adolescents: individual differences in salivary cortisol basal levels, diurnal variation, and responses to social challenges

The purpose of this study was to examine adrenocortical activity (basal, diurnal variation, and responses to social stressors) in adolescents at risk for psychopathology. Salivary cortisol levels were examined in normally developing and at-risk youth with internalizing and externalizing symptoms ranging from subclinical to clinical levels. Adolescents showed expected patterns of diurnal variation, with high early morning cortisol levels and a pattern of decline throughout the day. Females showed higher midday and late afternoon levels than males, and these patterns interacted with risk status. Internalizing problems sometimes were associated with gradual rather than steep declines in basal cortisol production. Both immediate and delayed cortisol reactivity to a social performance stressor were associated with internalizing symptoms. There was no evidence of relations between externalizing problems and underarousal of the hypothalamic-pituitary-adrenal (HPA) system. These and other results suggest that gender is an important moderating factor linking psychopathology. development, and context with HPA axis functioning in adolescence.     

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.     

The mechanism of the diurnal periodicity of mitosis

Summary Inversion of the alternation of light and darkness during the 24-hour period resulted in a complete inversion of the diurnal rhythm of mitotic activity in the epithelium of the skin, cornea, tongue and esophagus. After removal of the adrenal or thyroid glands the diurnal fluctuations of the number of mitoses were preserved, but their range in the morning and evening hours was somewhat reduced. Diurnal fluctuations of mitotic activity, absent in control animals, were noted in mice fed only at night. When mice were fed only in the morning the diurnal fluctuations were changed in the interstinal and tongue epithelium. The diurnal fluctuation of the RNA and DNA content noted in the cells of different organs corresponded to the mitotic rhythm. When the animals were illuminated at night the time of the maximum nucleic acid content changed from the morning to the evening.Presented by Active Member AMN SSSR V. N. Chernigovskii