Stress-related Cortisol Research Articles

Developmental differences in infant salivary alpha-amylase and cortisol responses to stress

This study examined developmental differences in infants' salivary alpha-amylase (sAA) and cortisol levels and responses to the well-baby exam/inoculation stress protocol at 2, 6, 12, and 24 months of age. Mother-infant pairs (n=85; 45 girls) were assessed during well-baby visits and saliva was sampled before the well-baby exam/inoculation procedure (pre-test) and at 5, 10, and 20 min post-inoculation stress. Older infants (24 months) had higher levels of sAA than younger infants (2, 6 and 12 months). Stress-related sAA increases were evident at 6 and 12 months, but not at 2 or 24 months of age. Stress-related cortisol increases were present at 2 and 6 months, but not at older ages. Mothers had higher sAA levels than their infants, but did not show sAA or cortisol increases to their infants' inoculation. Pre-test, maternal and infant sAA levels were positively correlated (rs .47 to .65) at 6, 12, and 24 months of age, but not at 2 months. These findings suggest that the association between the sympathetic branch of the autonomic nervous system and the secretion of sAA develops between 2 and 6 months of age, when levels of sAA are responsive to exposure to a painful stressor.

No Effect of 5-Day Treatment with Acetylsalicylic Acid (Aspirin) or the Beta-Blocker Propranolol (Inderal) on Free Cortisol Responses to Acute Psychosocial Stress: A Randomized Double-Blind, Placebo-Controlled Study

Background: The characterization of an individual’s hypothalamic-pituitary-adrenal axis stress response is a main research topic in neuropsychobiology since alterations have been causally linked to several disease states. Over the last years, several studies focused on the identification of sources of inter- and intraindividual variability, but there is still a paucity of experimental data on the effect of different pharmaceuticals on cortisol responses to acute psychological stress. Therefore, in this randomized double-blind placebo-controlled study, we investigated the effect of treatment with two popular and clinically used pharmaceuticals on stress-related cortisol responses, namely acetylsalicylic acid (aspirin), a known prostaglandin synthesis inhibitor, and the beta-blocker propranolol (Inderal), a nonselective beta-receptor antagonist. Methods: For 5 days, 73 healthy subjects (50 men, 23 women; mean age 47.3 ± 7.7 years) received either a daily oral dose of 100 mg aspirin, 80 mg propranolol (Inderal), aspirin + propranolol, or placebo. After treatment, subjects were confronted with the Trier Social Stress Test, a widely-used standardized psychosocial stress protocol. Cortisol responses were measured by six saliva samples taken before and after the stress exposure. Results: Subjects showed a significant cortisol increase after stress (p < 0.0001). The four treatment groups did not differ in their cortisol responses (group effect p > 0.44; interaction p > 0.97). Additionally, controlling for gender, age, smoking status, body mass index, mean arterial blood pressure or pre-stress cortisol levels yielded similar results in the total sample as well as in the male or female subgroups, respectively. Conclusion: Neither short-term treatment with aspirin nor propranolol altered the acute free cortisol response to psychological stress in healthy adults.

Short-term meditation training improves attention and self-regulation

Recent studies suggest that months to years of intensive and systematic meditation training can improve attention. However, the lengthy training required has made it difficult to use random assignment of participants to conditions to confirm these findings. This article shows that a group randomly assigned to 5 days of meditation practice with the integrative body-mind training method shows significantly better attention and control of stress than a similarly chosen control group given relaxation training. The training method comes from traditional Chinese medicine and incorporates aspects of other meditation and mindfulness training. Compared with the control group, the experimental group of 40 undergraduate Chinese students given 5 days of 20-min integrative training showed greater improvement in conflict scores on the Attention Network Test, lower anxiety, depression, anger, and fatigue, and higher vigor on the Profile of Mood States scale, a significant decrease in stress-related cortisol, and an increase in immunoreactivity. These results provide a convenient method for studying the influence of meditation training by using experimental and control methods similar to those used to test drugs or other interventions.

Circadian clock resetting by arousal in Syrian hamsters: the role of stress and activity.

Circadian rhythms in the Syrian hamster can be markedly phase shifted by 3 h of wheel running or arousal stimulation during their usual daily rest period ("subjective day"). Continuous wheel running is predictive but not necessary for phase shifts of this "nonphotic" type; hamsters aroused by gentle handling without running can also show maximal shifts. By contrast, physical restraint, a standard stress procedure and thus presumably arousing, is ineffective. To resolve this apparent paradox, phase-shifting effects of 3-h sessions of restraint or other stress procedures were assessed. In a preliminary study, phase shifts to arousal by gentle handling were significantly potentiated by the cortisol synthesis inhibitor metyrapone, suggesting that stress-related cortisol release may inhibit phase shifts to arousal. Next, it was confirmed that restraint in the subjective day does not induce phase shifts, but behavioral observations revealed that it also does not sustain arousal. Restraint combined with noxious compressed air blasts did sustain arousal and induced a significant cortisol response compared with arousal by gentle handling but did not induce shifts. Restraint combined with continuous horizontal rotation was also ineffective, as was EEG-validated arousal via confinement to a pedestal over water. However, 3 h of resident-intruder interactions (an intense psychosocial stress) or exposure to an open field (a mild stress) did induce large shifts that were positively correlated with indexes of forward locomotion. The results indicate that large phase shifts associated with arousal in the usual sleep period are neither induced nor prevented by stress per se, but are dependent on the expression of at least low levels of locomotor activity. Sustained arousal alone is not sufficient.

Exploring the genetic background of stress using isogenic progenies of common carp selected for high or low stress-related cortisol response

Four homozygous (HomIso) and eight heterozygous isogenic (HetIso) strains of common carp were used in two separate experiments to examine the genetic background of a stress-related cortisol response due to a rapid temperature decrease. The homozygous sires (two high and two low) and dams (high and low) used to obtain the strains were selected based on their estimated breeding value for this trait at an age of 15 months (EBV 15). In both experiments, the strains were subjected to a 9 °C cold shock at an age of 5 months. The ranking in plasma cortisol levels of the HomIso strains was identical to the ranking in EBV 15 of the sires and the maximal difference of 350 nmol l −1 was similar to the expected difference based on these EBV 15's. Differences between the HetIso strains were smaller than expected, and influence of non-additive genetic effects could not be detected ( P DS=0.14). Estimated breeding values based on the performance of the androgenetic progeny (EBV 5) in experiment 1 and general combining abilities (GCA) of the sires and dams calculated in experiment 2 were positively correlated with the EBV 15 ( r not significantly different from 1), providing no evidence that the stress response at 5 and 15 months are different traits. Based on the results of these experiments, it can be argued that the best method to change the stress responsiveness of common carp would be through selective breeding (exploiting additive genetic effects) rather than through crossbreeding (exploiting non-additive genetic effects).

Heredity of stress-related cortisol response in androgenetic common carp ( Cyprinus carpio L.)

The aim of this paper was to estimate the heritability for the intensity of the stress-related cortisol response in common carp ( Cyprinus carpio L.) using androgenetic progeny groups. For this, 660 androgenetic individuals (age: 110 days) were subjected to a 9°C cold shock and blood sampled 20 min after onset of the shock. Heritabilities were estimated for weight, length, condition factor ( K), and plasma cortisol, glucose and lactate concentrations using Gibbs sampling. Estimated heritabilities for the morphological traits weight and length were 0.09 (90% highest posterior density (HPD) range: 0.03–0.17) and 0.11 (0.04–0.21), respectively. The condition factor ( K), showed a medium heritability of 0.37 (0.20–0.62). Heritabilities for basal plasma glucose and lactate were 0.19 (0.10–0.33) and 0.56 (0.33–0.85), respectively. For stress-related cortisol increase, a high heritability estimate of 0.60 (0.37–0.90) was found. Although the height of this cortisol heritability has to be regarded with some reservation, due to confounding of some environmental effects with sire effects, the estimated heritability clearly shows that the intensity of the stress response due to a cold shock is heritable in the carp population used.

Experience and endocrine stress responses in neonatal and pediatric critical care nurses and physicians.

Critical care is a working environment with frequent exposure to stressful events. High levels of psychological stress have been associated with increased prevalence of burnout. Psychological distress acts as a potent trigger of cortisol secretions. We attempted to objectify endocrine stress reactivity. Observational cohort study during two 12-day periods in successive years. A tertiary multidisciplinary neonatal and pediatric intensive care unit (33 beds). One hundred and twelve nurses and 27 physicians (94% accrual rate). Cortisol determined from salivary samples collected every 2 hrs and after stressful events. Participants recorded the subjective perception of stress with every sample. Endocrine reactions were defined as transient surges in cortisol of >50% and 2.5 nmol/L over the baseline. During 7,145 working hours, we observed 474 (12.5%) endocrine reactions from 3,781 samples. The mean cortisol increase amounted to 10.6 nmol/L (219%). The mean occurrence rate of endocrine reactions per subject and sample was 0.159 (range, 0-0.43). Although the mean raw cortisol levels were lower in experienced team members (>3 yrs of intensive care vs. <3 yrs, 4.1 vs. 4.95 nmol/L, p < .001), professional experience failed to attenuate the frequency and magnitude of endocrine reactions, except for the subgroup of nurses and physicians with >8 yrs of intensive care experience. A high proportion (71.3%) of endocrine reactions occurred without conscious perception of stress. Unawareness of stress was higher in intensive care nurses (75.1%) than in intermediate care nurses (51.8%, p < .01). Stress-related cortisol surges occur frequently in neonatal and pediatric critical care staff. Cortisol increases are independent of subjective stress perception. Professional experience does not abate the endocrine stress reactivity.

The metabolic syndrome--a neuroendocrine disorder?

Central obesity is a powerful predictor for disease. By utilizing salivary cortisol measurements throughout the day, it has now been possible to show on a population basis that perceived stress-related cortisol secretion frequently is elevated in this condition. This is followed by insulin resistance, central accumulation of body fat, dyslipidaemia and hypertension (the metabolic syndrome). Socio-economic and psychosocial handicaps are probably central inducers of hyperactivity of the hypothalamic-pituitary adrenal (HPA) axis. Alcohol, smoking and traits of psychiatric disease are also involved. In a minor part of the population a dysregulated, depressed function of the HPA axis is present, associated with low secretion of sex steroid and growth hormones, and increased activity of the sympathetic nervous system. This condition is followed by consistent abnormalities indicating the metabolic syndrome. Such 'burned-out' function of the HPA axis has previously been seen in subjects exposed to environmental stress of long duration. The feedback control of the HPA axis by central glucocorticoid receptors (GR) seems inefficient, associated with a polymorphism in the 5' end of the GR gene locus. Homozygotes constitute about 14% of Swedish men (women to be examined). Such men have a poorly controlled cortisol secretion, abdominal obesity, insulin resistance and hypertension. Furthermore, polymorphisms have been identified in the regulatory domain of the GR gene that are associated with elevated cortisol secretion; polymorphisms in dopamine and leptin receptor genes are associated with sympathetic nervous system activity, with elevated and low blood pressure, respectively. These results suggest a complex neuroendocrine background to the metabolic syndrome, where the kinetics of the regulation of the HPA axis play a central role.

Food-induced cortisol secretion in relation to anthropometric, metabolic and haemodynamic variables in men.

To assess the relationships between the regulation of diurnal and food-induced cortisol secretion and anthropometric, metabolic and haemodynamic variables in middle-aged men. Salivary cortisols were collected repeatedly (n = 7) over an ordinary working day (8a.m. to 11 p.m.) in a randomly selected population of 284 men, aged 51 y. A standardized lunch was provided, and an overnight low-dose dexamethasone suppression test was performed. These measurements were correlate with the anthropometric factors-body mass index, BMI, (kg/m2), waist-to-hip ratio (WHR) and abdominal sagittal diameter; the metabolic factors-fasting insulin and glucose as well as their ratio, and triglycerides; and the haemodynamic factors-systolic and diastolic blood pressures and heart rate. As reported previously two principal types of salivary cortisol secretory patterns can be singled out, one characterized by high morning cortisol levels, a normal circadian rhythm and feedback regulation (dexamethasone) along with a brisk cortisol response to lunch, and another, found in a limited number of men, characterized by low morning cortisols, the absence of a circadian rhythm, a relative resistance to dexamethasone inhibition and a poor lunch-induced cortisol response. The normal cortisol secretory pattern showed negative associations with BMI (P< 0.05), WHR (P< 0.01), and blood pressures (P< 0.001). After stimulation by food intake, negative relationships were found with all obesity measurements, insulin, insulin/glucose ratio, triglycerides, blood pressures and heart rate (all P < 0.001). These results suggest that normally regulated cortisol is associated with a favourable somatic health. In contrast, after food intake cortisol secretion, based on an abnormal cortisol secretory pattern, showed consistent positive associations with obesity measurements, insulin, glucose and insulin/glucose ratio, triglycerides, blood pressures and heart rate (all P < 0.001). A normal HPA axis regulation is associated with excellent health anthropometric, metabolic and haemodynamic variables, particularly visible after the physiological stimulus of food intake. This is, however, not the case in men with perturbed HPA axis function where associations in these somatic variables become exaggerated by food intake. We have previously reported that perceived stress-related cortisol is associated with abnormalities in the variables mentioned above, both with a normal and, particularly, with an abnormal function of the HPA axis. It is thus apparent that perceived stress and food intake show separate associations to somatic variables with a normally functioning HPA axis, while with an abnormal regulation of this axis both perceived stress and food intake exaggerate associations to abnormal somatic variables.

Hypothalamic arousal, insulin resistance and Type 2 diabetes mellitus.

Type 2 diabetes mellitus (DM) develops when insulin resistance overcomes the capacity of compensatory insulin secretion. Insulin resistance may be induced via psychoneuroendocrine pathways, a possibility which has received little previous attention. We have used salivary cortisol measurements to monitor the activity of the hypothalamic-pituitary-adrenal (HPA) axis, the major controller of hormones involved in the regulation of peripheral insulin sensitivity under everyday conditions. The influence of external challenges, as well as the sensitivity of feedback regulation, were followed in randomly selected middle-aged population samples. In health there is a rhythmicity of cortisol secretion, with a high plasticity and efficient feedback control. In contrast, a group of subjects were identified with a flat, rigid day curve and poor feedback control, who showed consistent abnormalities in stress-related cortisol secretion, including inhibited secretions of sex steroids and growth hormone; insulin resistance; abdominal obesity; elevated leptin levels; hyperglycaemia; dyslipidaemia and hypertension with elevated heart rate. The endocrine abnormalities are probably responsible for the anthropometric and metabolic abnormalities. The circulatory perturbations seem to be induced by a parallel activation of the central sympathetic nervous system suggesting an 'hypothalamic arousal syndrome', gradually developing into an independent risk for disease. An associated cluster of environmental factors, including psychosocial and socio-economic stress, traits of depression and anxiety, alcohol consumption and smoking, all factors known to activate hypothalamic centres, has been identified. A polymorphism of the glucocorticoid receptor gene, with 13.7% homozygotes in the male Swedish population, parallels receptor dysfunction, and may be responsible for the associated insulin resistance, central obesity and hypertension. This is the first detailed examination of psychoneuroendocrinological processes in the natural environment on a population basis in relation to somatic health. The results suggest that an hypothalamic arousal syndrome, with parallel activation of the HPA axis and the central sympathetic nervous system, is responsible for development of endocrine abnormalities, insulin resistance, central obesity, dyslipidaemia and hypertension, leading to frank disease, including Type 2 DM. We suggest that this syndrome is probably based on environmental pressures in genetically susceptible individuals.

Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities.

Abdominal obesity has been suggested to be associated with perturbations of the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In a population of 51-yr-old men (n = 284) salivary cortisol concentrations were determined on repeated (n = 7) occasions over a random working day, and perceived stress was reported in parallel. Cortisol values were then related to reported stress (stress-related cortisol). A standardized lunch was used as a physiological challenge. A low dose (0.5 mg) dexamethasone suppression test was also performed as well as determinations of testosterone and insulin-like growth factor I (IGF-I). Body mass index [weight (kilograms)/height (meters)2]; waist/hip circumference ratio (WHR); sagittal trunk recumbent diameter (D); fasting insulin; blood glucose; triglycerides; and total, low density (LDL), and high density (HDL) lipoprotein cholesterol were also determined. Cortisol concentrations were highest in the morning, and lunch was followed by a peak (P = 0.044). Two types of diurnal cortisol curves were identified, one characterized by a high variability with high morning values, and another with low variability and low morning values. Both correlated strongly with suppression of salivary cortisol by dexamethasone (P < 0.001). Stress-related cortisol secretion was associated with D (P = 0.051), low IGF-I (P = 0.006), and diastolic blood pressure (P = 0.078). When the type of diurnal cortisol curve was taken into consideration by statistical weighting, stress-related cortisol secretion in subjects with high variability showed associations with testosterone (P < 0.001), D, total and LDL cholesterol, diastolic blood pressure (P < 0.001), fasting insulin (P = 0.039), and glucose (P = 0.030) as well as, negatively, triglycerides (P < 0.001). When weighted for a low variability of diurnal cortisol secretion, stress-related cortisol secretion showed strong negative relationships with IGF-I, testosterone, and HDL. Furthermore, strong, consistent relationships (all P < 0.001) were found with obesity factors (body mass index, WHR, and D), and with metabolic (insulin, glucose, triglycerides, and total and LDL cholesterol) as well as hemodynamic variables (systolic and diastolic blood pressure and heart rate). These results clearly show interactions between diurnal cortisol secretion related to perceived stress and anthropometric, endocrine, metabolic, and hemodynamic variables. This seems to occur with apparently normal regulation of the HPA axis (high morning peaks and variability as well as dexamethasone suppression of cortisol), where other endocrine variables are not affected. With a low diurnal cortisol variation and blunted dexamethasone suppression, indicating abnormal regulation of the HPA axis, perceived stress-dependent cortisol values were strongly related to perturbations of other endocrine axes as well as abdominal obesity with metabolic and hemodynamic abnormalities. Perturbations of the regulations of the HPA axis such as those described in combination with low dexamethasone suppressibility are known to follow long term overactivation of the axis by factors such as environmental stress.

Stress-Related Cortisol Secretion in Men: Relationships with Abdominal Obesity and Endocrine, Metabolic and Hemodynamic Abnormalities

Stress-Related Cortisol Secretion in Men: Relationships with Abdominal Obesity and Endocrine, Metabolic and Hemodynamic Abnormalities

Developmental Change in Infants' Responses to Stress

Infant stress responses to a well-baby physical examination and inoculation were observed longitudinally at 2, 4, and 6 months of age. In general, there were cortisol increases over base to the procedures. Cortisol level and cortisol response decreased with age. These data indicate a developmental shift in adrenocortical functioning between 2 and 6 months of age. Further evidence for this shift was seen in the stability of individual responses between 4 and 6 months of age. Individual differences in both cortisol and behavioral responses showed the most stability between these 2 ages. Moreover, diurnal variation in baseline cortisol level was present only at 6 months of age. While a sizable minority of infants showed stress-related cortisol decreases to the procedures at a given age, there was no evidence for cross-age consistency in individual infants showing these cortisol decreases.

Stress-related cortisol levels in channel catfish ( Ictalurus punctatus) plasma do not affect peripheral amino acids chemoreception

1. 1. Electrophysiological responses of the channel catfish barbels gustatory system to 10 −4M of two amino acids, l-alanine and l-arginine, were monitored following transportation of the fish to the laboratory's holding tanks. 2. 2. During the entire monitoring period, up to 20 days post-transportation, only small changes in gustatory response were observed, which were not correlated with changes in plasma cortisol levels, which were used as a stress indicator. 3. 3. Injecting channel catfish with cortisol produced no significant effect on gustatory perception of the two amino acids tested, although it accelerated liver glycogen depletion.

The effects of metabolic stress on plasma progesterone in healthy volunteers and schizophrenic patients

A number of preclinical studies suggest that progesterone may play an important role in the stress response, however, the effects of stress on progesterone in humans has not been established. Also, several lines of evidence indicate that schizophrenia may be associated with abnormal neurobiological responses to stress, but the effects of stress on progesterone in schizophrenia has not been investigated. The purpose of the present study was to examine the effects of stress on plasma progesterone and cortisol in healthy subjects and to determine if schizophrenic patients have altered stress-induced plasma progesterone levels compared to normal controls. Stress was induced through administration of 2-deoxyglucose (2DG), a glucose analog that impairs glucose metabolism resulting in a clinical state comparable to hypoglycemia. There were significant increases in plasma progesterone and cortisol levels following 2DG-induced glucoprivic stress in healthy controls. There was no relationship between stress related progesterone and cortisol elevations. Schizophrenic patients, in comparison to controls, had significantly greater 2DG-induced elevations in progesterone levels but no differences in stress-related cortisol levels. There was evidence that basal progesterone and cortisol levels were elevated in the schizophrenic patients. The implications of these data are discussed.