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.     

C-reactive protein polymorphisms are associated with the cortisol awakening response in basal conditions in human subjects

Cortisol affects the acute-phase response, but it is unknown whether C-reactive protein (CRP), an acute-phase reactant, also affects hypothalamus?pituitary?adrenal axis activity. In the present study, associations were explored between CRP haplotypes with plasma CRP concentrations and basal salivary cortisol level. We included 266 physically healthy Caucasian subjects (103 females and 163 males) aged between 18 and 65 years of whom 94 had a psychiatric disorder in a genetic association study. Six tag single-nucleotide polymorphisms capturing the common genetic variation of the CRP gene were genotyped (i.e. rs2808628, rs2808630, rs1205, rs1800947, rs1417938, and rs3091244) to yield common CRP haplotypes. Plasma CRP concentrations, the salivary cortisol awakening response (CAR) (0, 30, 45, and 60?min after awakening), and the diurnal cortisol decline (11:00, 15:00, 19:00, and 23:00 h) were assessed for 2 days. rs2808628, rs1205, rs1417938, and rs3091244 showed expected associations not only with CRP concentrations, but also with salivary cortisol levels during the CAR. Five well-characterized CRP haplotypes were arranged in ascending order according to increasing CRP levels. There was an inverse linear association between CRP haplotypes and cortisol levels during the CAR, but no association with the diurnal cortisol decline. Hence, genetic variants in the CRP gene that are associated with lifetime plasma CRP levels were also associated with salivary cortisol levels after awakening, in basal, non-inflammatory conditions.     

Urinary cortisol responses to unusual events in captive chimpanzees (Pan troglodytes)

This study investigated the urinary cortisol stress response to one known stressor (anaesthesia) and three unusual events hypothesized to result in increases in cortisol (confinement to one half of an enclosure for several days due to a hurricane, an enrichment exercise, and a change in group composition) in young chimpanzees (Pan troglodytes). Although a cortisol stress response to a variety of laboratory experiences has been documented in captive animals, it is unclear whether other types of atypical events are stressful, including those that are not necessarily negative. Cortisol was measured in 519 urine samples collected from 20 awake, unrestrained chimpanzees; individuals were compared against their own baseline values. A significant increase in urinary cortisol concentration was found as a result of the stress of anaesthesia, but no significant change in urinary cortisol resulted from the three other potential stressors. A lack of a urinary cortisol response to these events may indicate that the events were not actually stressful for the chimpanzees, but may have resulted from the limited temporal resolution of measuring cortisol excretion as an indicator of integrated secretion, or from changes in rates of agonistic behaviors.     

A follow-up of cognitive performance and diurnal salivary cortisol changes in former burnout patients

The purpose of this study was to determine whether recovery from burnout is associated with improved cognitive functioning, and whether such improvement is associated with changes in hypothalamic-pituitary-adrenal axis activity and return to work. Forty-five former burnout patients were followed up after 1.5 years with a neuropsychological examination, diurnal salivary cortisol measurements, dexamethasone suppression test (DST), and self-ratings of cognitive problems. At follow-up, improved cognitive performance was observed on several tests of short-term memory and attention. Self-rated cognitive problems decreased considerably, but this decrease was unrelated to the improvement on neuropsychological tests. Diurnal salivary cortisol concentrations at awakening, 30?min after awakening, and in the evening, did not change from baseline to follow-up, nor did the cortisol awakening response. However, slightly, but significantly, stronger suppression of cortisol in response to the DST was observed at follow-up. Improvements in subjective or objective cognitive functioning and changes in diurnal cortisol concentration were unrelated to the extent of work resumption. However, a decreased DST response at follow-up was partially related to improved cognitive performance and work resumption. The clinical implications are that burnout seems to be associated with slight and significantly reversible cognitive impairment, and that self-rated cognitive change during recovery poorly reflects objective cognitive change.     

Maternal prenatal stress and 4-6 year old children's salivary cortisol concentrations pre- and post-vaccination

In this study influences of maternal prenatal stress on the cortisol reactions of children to a vaccination were determined. Prenatal stress at around 16 weeks of gestation was measured through questionnaires and a cortisol day curve. Cortisol reactions were determined preceding and following the vaccination. A total of 24 children (age between 3.11 and 5.9 years, mean age 4.9 years) and their mothers participated in this study. Multilevel analysis (hierarchical linear modelling) was used to analyze the data. Children of mothers who had higher concentrations of morning cortisol during pregnancy had higher concentrations of cortisol as compared to children of mothers who had lower concentrations of morning cortisol. Furthermore, more daily hassles and a higher level of fear of bearing a handicapped child during pregnancy were associated with higher concentrations of cortisol in the children.     

Differences between diurnal patterns of salivary cortisol and dehydroepiandrosterone in healthy female adolescents

The adrenal hormones cortisol and dehydroepiandrosterone (DHEA) share a common secretagogue: adrenocorticotropic hormone; however, secretion of these hormones can be dissociated suggesting subtle individual regulation at the level of the adrenal gland. We examined differences in the diurnal patterns of cortisol and DHEA secretion in healthy adolescent girls, with the aim of informing the possibility of exploiting these differences to aid interpretation of data from clinical populations in which these patterns can become dysregulated. Fifty-six healthy females aged 10-18 years provided saliva samples at 0 and 30 min (morning samples) and 12 h post-awakening on 2 consecutive weekdays. For morning salivary cortisol in relation to morning DHEA concentrations, correlational analysis revealed only a trend (p = 0.054). Similarly, the association between evening cortisol and DHEA was characterised as a trend (p = 0.084). Mean morning DHEA concentrations showed more day-to-day consistency than equivalent cortisol samples (r = 0.829 for DHEA and 0.468 for cortisol; z = 3.487, p < 0.0005). Unlike the cortisol pattern, characterised by a marked awakening response (cortisol awakening response, CAR), a significant rise in DHEA concentration post-awakening was not evident. Finally, there was a strong association between morning and evening concentrations of DHEA, not found for cortisol. The study shows differences in cortisol and DHEA secretion in the post-awakening period and informs work that seeks to examine correlates of dysregulated hypothalamic-pituitary-adrenal axis function. Parallel examination of both hormones enables enhanced interpretation of aberrant patterns of the CAR, i.e. an exploration of whether dysregulation affects both hormones (reflecting overall steroidogenic capacity) or cortisol alone (CAR-specific mechanisms).     

Effects of various hippocampal lesions on monkey plasma cortisol levels in two experimental conditions

The plasma cortisol levels of Rhesus monkeys with anterior, posterior, or near-total hippocampal lesions were compared to controls during two separate stressful conditions. In the first condition, each monkey was placed for the first time in a primate restraint chair for 72 h. In the second condition each monkey performed a complex behavioral task (titrating shock avoidance) to control the intensity of frequent footshock for a 24-h period. Control subjects had either no surgical operation or else surgical exposure of the hippocampus with no hippocampal lesion. They manifested lower plasma cortisol levels during shock avoidance compared with during the chair condition. Subjects with posterior hippocampal lesions manifested the same pattern but near-totally hippocampectomized subjects showed an opposite pattern with cortisol levels higher in the shock avoidance condition compared with the chair condition. Subjects with anterior hippocampal lesions had similar cortisol levels in both conditions. Thus hippocampal modulation of corticosteroid levels may depend on the specific condition under which such levels are measured, and may be relatively more subserved by anterior compared with posterior hippocampus in the monkey.     

Cortisol and behavioral responses to separation in mother and infant guinea pigs

In Experiment 1, lactating guinea pigs 3 days postpartum exhibited an elevation of plasma levels of cortisol when their litters were taken from the home cage and placed out of auditory range for 30 min. If pups were left within auditory range during the period of separation, or if the litter was disturbed but not removed, no increase in plasma cortisol levels was observed. In Experiment 2, 11/12- and 18/19-day-old guinea pig pups placed alone in a novel environment for 30 min displayed levels of plasma cortisol and vocalizations that were greater than those of pups tested in the same environment but with their mother. Pups tested with littermates but not with their mother exhibited plasma cortisol levels that were as great as those of pups tested alone. Pups tested with littermates vocalized much less than pups tested alone but more than pups tested with their mother. These results indicate that brief mother-infant separation can activate the pituitary-adrenal system in mother as well as infant guinea pigs and they provide further evidence for the existence of a reciprocal mother-infant attachment in this species.     

Serum testosterone,cortisol, glucose,and ethanol in males arrested for spouse abuse

Concentrations of ethanol, testosterone, cortisol, and glucose were determined in serum obtained from 16 males taken into police custody after incidents of spouse abuse. The mean blood ethanol level at the time of arrest was 33.3 ± 2.6 mM. Serum testosterone levels were significantly lower and cortisol levels higher at the time of police intervention (within 1 hour of the incident) compared to control data collected later from the subjects when sober. Offenders did not differ from a group of nonviolent pub patrons at similar blood ethanol levels (35.9 ± 4.5 mM) with respect to serum testosterone, cortisol, or glucose, but their sober state cortisol and glucose concentrations were significantly higher compared to a control group of nonalcoholic men. Intoxication or acute hormonal changes were thus not specifically associated with violent behaviour. Provocative cues, however, may have been more frequent in the offender families, as Straus Conflict Tactics data showed that offenders and victims resorted to verbal aggression significantly more often than control families. The significantly elevated cortisol and glucose concentrations in offenders when sober compared to nonviolent controls could be viewed as direct effects of life stress, or as indirect effects of stress mediated by learned escape drinking. Excessive drinking as well as spouse abuse could be maladaptive coping strategies that principally serve to maintain the status quo, physiologically as well as psychologically. © 1992 Wiley-Liss, Inc.     

Effect of a kickboxing match on salivary cortisol and immunoglobulin A

The hypothesis that salivary cortisol would increase and salivary immunoglobulin A (IgA) decrease after a kickboxing match was tested among 20 male athletes. Saliva samples collected before and after the match were analyzed. Salivary cortisol and salivary IgA concentrations (absolute concentration, salivary IgAabs) and the secretion rate of IgA (salivary IgArate) were measured by enzyme-linked immunosorbent assay. A Wilcoxon test for paired samples showed significant increases in salivary cortisol from pre- to postmatch. No significant changes were observed in salivary IgAabs or secretory IgArate and saliva flow rate. This study indicates that a kickboxing match might increase salivary concentration and thereafter it could be considered a significant source of exercise-related stress. On the other hand, the effect of a kickboxing match on mucosal immunity seems not to be relevant.     

Intranasal oxytocin and salivary cortisol concentrations during social rejection in university students

Oxytocin facilitates pro-social behaviour and is proposed as a regulatory factor controlling stress reactivity. Previous research on oxytocin and stress has focused on achievement-related stressors among male participants. The aims of the study were to (1) examine the influence of oxytocin on the affective and cortisol response to the Yale Interpersonal Stressor (YIPS), a live social rejection paradigm, and (2) to replicate the finding that women exhibit a greater cortisol response to interpersonal stress than men (Stroud et al. 2002). Sex differences in stress responses: Social rejection versus achievement stress. Biol Psychiat 53:318-327. Ninety-six undergraduate students underwent the YIPS, where participants were excluded from two separate conversations by two same-sex confederates. Salivary cortisol concentrations and mood were repeatedly measured throughout the study. Participants were administered, in a double-blind design, a single dose of intranasal oxytocin (24 IU) or placebo prior to beginning the YIPS. The YIPS elicited a significant negative mood response that was more pronounced in females than in males. However, no significant cortisol response to the stressor and no sex difference in cortisol reactivity were observed. A significant effect of drug condition on cortisol levels was observed. Participants who were administered oxytocin exhibited a decrease in cortisol levels, relative to placebo, during the YIPS, F (4, 184)=4.50, p<0.05. The study failed to replicate the sex difference in the cortisol response to interpersonal stress reported by Stroud et al. (2002). Intranasal oxytocin, however, appeared to reduce cortisol concentrations during an interpersonal challenge.     

Endogenous cortisol level interacts with noradrenergic activation in the human amygdala

Animal studies show that high cortisol levels exert their effect on stressful task performance via modulation of the amygdala. Availability of noradrenaline in this brain region appears to be a critical prerequisite for this effect. This relationship between noradrenaline and cortisol is explained by an animal model where the amygdala constitutes a crucial region for this interaction. In humans this model has not been extensively tested so far. In a previously reported study human subjects (aged 20.93+/-2.38) were scanned using fMRI when watching sets of emotional and neutral pictures after taking the beta-adrenergic antagonist propranolol or placebo. Stimulus sets consisted of 92 pictures, divided in four emotional categories that ranged from neutral scenes of domestic objects (CAT1) to extremely negative scenes of mutilation or accidents (CAT4). Confrontation with arousing emotional pictures, accompanied by increased noradrenaline levels, evoked increased amygdala activation under placebo but not under betablocker condition. This new and additional analysis of this data set was carried out to determine the effect of differential endogenous cortisol levels on amygdala activation. Cortisol levels during scanning were determined using salivary samples and subjects were post hoc divided in a High (n=14) and Low cortisol group (n=14). When subjects were watching emotional stimuli, presumably associated with enhanced noradrenaline (NA) levels, amygdala activation was contrasted between the two cortisol groups. We hypothesized that emotional stimuli would elicit more amygdala activation in the High than in the Low cortisol group. Here we demonstrate indeed a significant interaction effect of the endogenous cortisol level with increasing activation in the amygdala under placebo but not under betablocker condition, thereby extending the rodent based model of a synergistic effect of the two stress hormones to the human.     

Diurnal patterns of salivary cortisol and DHEA in adolescent anorexia nervosa

Although there is well-documented evidence for hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis function in anorexia nervosa (AN), there has been little research into secretory patterns of salivary cortisol and dehydroepiandrosterone (DHEA) in this condition. The cortisol awakening response (CAR), a prominent and discrete feature of the cortisol cycle, has not been extensively explored in adolescent AN. Saliva samples were collected at awakening, 30?min and 12 h post-awakening on two consecutive weekdays from eight female adolescents with clinically diagnosed AN and 41 healthy control (HC) age-matched females. Adolescent AN patients had greater salivary cortisol and DHEA concentrations than HC girls at all points. Increased hormone secretion was unrelated to body mass index. However, despite hypersecretion of both hormones, the circadian pattern including the CAR paralleled that of the HC group. Findings from this preliminary study confirm dysregulation of HPA axis function in adolescent AN as evidenced by hypersecretion of both cortisol and DHEA, which share the common secretagogue adrenocorticotropic hormone. However, the parallel diurnal profiles for AN and HC participants, including the CAR, may indicate hypersecretion per se rather than differential regulation of the diurnal pattern of these two adrenal steroids in AN.     

Sex differences of salivary cortisol secretion in patients with major depression

Depression is associated with increased cortisol secretion and occurs more often in women than in men. Thus, it has been hypothesized that differences in cortisol secretion might, in part, be responsible for the greater risk of developing depression in women. However, only few studies have examined sex differences in baseline cortisol secretion in depressed patients and healthy controls. We examined sex effects on cortisol secretion in 52 medication-free patients with major depression (37 women, 15 men, mean ± SD age 35 ± 11 years, Hamilton Depression Scale mean score 27 ± 5) and 50 healthy age- and sex-matched control subjects. Salivary cortisol concentrations were measured at 8:00, 12:00, 16:00, and 22:00 h. Repeated measures analysis of covariance revealed a group × sex interaction (p = 0.05). Post hoc tests revealed higher cortisol concentrations in depressed compared to healthy men [F(1;29) = 7.5, p = 0.01]. No differences were found between depressed and non-depressed women. Our results do not support the hypothesis that differences in cortisol secretion between depressed and non-depressed subjects are more pronounced in women than in men. Study characteristics and methods as well as sex-specific confounding variables such as menstrual cycle, menopause and the use of oral contraceptives may account for inconclusive results across studies.     

Academic self-concept of ability and cortisol reactivity

The present study aimed to clarify the relationship between a school-specific trait (academic self-concept of ability [ASCA]) and hormonal stress response by using a trait-compatible stressor (test). First, we determined 52 students' ASCA scores for biology and measured their salivary cortisol concentration before and after a biology test (experimental group, n = 28) or a free writing task (control group, n = 24). For participants who took the test, statistical analysis indicated a significant negative correlation between ASCA score and cortisol response. In contrast, the control group showed a decrease in cortisol concentrations between test times and no correlation between cortisol concentration and ASCA scores were found. These findings indicated an interaction between ASCA scores and hormonal stress response when an academic-related stressor is present. Furthermore, these variables might influence each other adversely: high cortisol concentrations during a test situation may lead to greater feelings of insecurity, resulting in low ASCA scores and awareness of these low scores may lead to a further increase in cortisol, creating a vicious cycle.     

The social endocrinology of dominance: basal testosterone predicts cortisol changes and behavior following victory and defeat

Past research suggests that individuals high in basal testosterone are motivated to gain high status. The present research extends previous work by examining endocrinological and behavioral consequences of high and low status as a function of basal testosterone. The outcome of a competition--victory versus defeat--was used as a marker of status. In Study 1, high testosterone men who lost in a dog agility competition rose in cortisol, whereas high testosterone men who won dropped in cortisol. Low testosterone men's cortisol changes did not depend on whether they had won or lost. Study 2 replicated this pattern of cortisol changes in women who participated in an experimental laboratory competition, and Study 2 extended the cortisol findings to behavior. Specifically, high testosterone winners chose to repeat the competitive task, whereas high testosterone losers chose to avoid it. In contrast, low testosterone winners and losers did not differ in their task preferences. These results provide novel evidence in humans that basal testosterone predicts cortisol reactivity and behavior following changes in social status. Implications for the social endocrinology of dominance are discussed.     

Salivary concentrations of cortisol and testosterone and prediction of performance in a professional triathlon competition

The aim of this study was to examine salivary cortisol and testosterone concentrations in professional male athletes during a short triathlon competition using non-invasive methods, and to determine whether these hormone concentrations could be accurate predictors of performance. Eight adult male athletes (age, mean ± SEM: 27.8 ± 3.2 years; body mass index: 21.66 ± 0.42) in a professional triathlon team volunteered to participate in this study. Saliva samples were taken on the competition day and 7 days after competition on a rest day. The performance of the athletes was assessed by their rank order in the competition. Salivary cortisol concentrations were greater on the competition day than on the rest day in the early morning, immediately after waking up, 30 min later, immediately before the start of the competition, and later in the evening. Testosterone concentrations were greater on the competition day in the morning and in the evening. The diurnal rhythm of both cortisol and testosterone concentrations was maintained on both days and the testosterone/cortisol ratio (T/C ratio) was similar between days. The performance of the athletes was positively correlated with salivary cortisol concentration in the early morning of the competition day, but was not correlated with testosterone concentrations at any of the time points. In conclusion, early morning salivary cortisol concentration, but not T/C ratio, could be used to predict performance in athletes during a professional triathlon competition.     

Salivary cortisol concentrations, stress and quality of life in women with endometriosis and chronic pelvic pain

The objective of this study was to evaluate the perceived stress index, quality of life, and hypothalamus-pituitary-adrenal axis activity in women with endometriosis and chronic pelvic pain. For the study, 93 women with endometriosis and 82 healthy women volunteered. The visual analogue scale (VAS) (0=no pain; 10=severe pain) was used to determine pain intensity; the perceived stress questionnaire (PSQ) defined stress index, and the health-related quality-of-life (HRQOL)-SF-36 questionnaire was used to evaluate quality of life. Salivary cortisol was measured at 0800, 1600, and 2000 h and the awakening cortisol response was assessed to evaluate the hypothalamus-pituitary-adrenal axis activity. The results show that women with endometriosis and chronic pelvic pain of moderate intensity (4.1+/-0.58, mean+/-SEM) have higher levels of perceived stress (0.55+/-0.01 versus 0.42+/-0.01, p<0.05), a poorer quality of life expressed as lower scores for all items of the inventory and hypocortisolism. Lower levels of salivary cortisol were observed in all three samples collected, as well as in the awakening cortisol response, for women with endometriosis (0.19+/-0.09 microg/dl) when compared with controls (0.78+/-0.08 microg/dl, p<0.05 l), and it was independent of pain intensity and Mental health (MH) scores in SF-36. We concluded that women with endometriosis and chronic pelvic pain show low concentrations of salivary cortisol and a high level of perceived stress, associated with a poor quality of life. Whether the hypocortisolism was an adaptive response to the aversive symptoms of the disorder or a feature related to the etiology of endometriosis remains to be elucidated.     

Stress and stereotypic behaviour in mink (Mustela vison): a focus on adrenocortical activity

We examined whether female mink with low (LS) and high (HS) occurrence of stereotypic behaviour differ in their adrenocortical activity in baseline conditions or in response to immobilisation (Experiment 1), handling, adrenocorticotropic hormone (ACTH) challenge (Experiment 2) and excretion of circulating cortisol (Experiment 3). Faeces are the predominating excretory route of cortisol (83%), with peak concentrations after 4.2 h (urine: 3.4 h). Faecal cortisol metabolites (FCMs) reflected changes in relation to handling/ACTH challenge. In Experiment 1 (n = 162), HS mink had approximately 54% higher baseline level of FCM than LS mink (P < 0.001), with markedly elevated FCM on the days after an immobilisation stressor. In Experiment 2 (n = 48), LS and HS mink did not differ in adrenocortical activity after an ACTH challenge. However, HS mink reacted more in response to handling, evident in the FCM level 4-20 h after the handling (P = 0.001). In Experiment 3 (n = 16), the excretion of infused (3)H-cortisol did not differ between LS and HS mink. Stereotypic behaviour is concurrent with higher baseline concentrations of FCM, which cannot be explained by a greater adrenocortical reactivity or a different excretion of the circulating cortisol. Instead, we conclude that mink with a high level of stereotypic behaviour have a greater perception of stress, or increased sensitivity to stressors at the pituitary level.     

Rhesus plasma cortisol response at four dominance positions

Adrenocortical function and social behaviors were measured in 48 laboratory-born juvenile monkeys in stable (original) groupings at rest, in the same groupings in competition for drinking water, in newly formed groupings each composed of animals from the same original dominance position, and upon return to the original groupings, always in groups of four. In newly formed groupings, plasma cortisol measured higher with each step down in the new dominance hierarchy, the effect attenuating by day 8. Although the partial correlation between frequencies of hostility behavior and plasma cortisol level was low (r = 0.05) when holding fear constant, the partial correlation between cortisol and fear behaviors, holding hostility behavior constant, was 0.86. The data provide evidence that corticosteroid elevations during social stress are related to behavior suggestive of fear and not aggression and are dependent upon dominance rank, the level of dominance competition, and previous dominance history.