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Biomedical subjects

C Kirschbaum

Publications and source records attributed to C Kirschbaum.

At least 37 records · Page 2Linked to original sources
PubMed1999

The cortisol response to awakening in relation to different challenge tests and a 12-hour cortisol rhythm.

Recent studies have shown that cortisol levels rapidly increase within the first 30 minutes after awakening. This response is rather robust over weeks or months and is altered by chronic stress and burnout. The present study investigated to what extent the cortisol response to awakening relates to responses following hCRH, ACTH(1-24), or psychosocial stress challenges in 22 healthy subjects. Furthermore, a 12-hour circadian cortisol profile was obtained to compare the morning response with cortisol levels obtained throughout the day. Results show that the morning cortisol response was of similar magnitude to that following injection of 1 microg/kg h-CRH or exposure to a brief psychosocial stressor (TSST). All of these were significantly smaller compared to maximal stimulation of the adrenal cortex by ACTH(1-24). Correlation analyses revealed that the morning cortisol response was closely related only to the cortisol response following 0.25 mg ACTH(1-24) (r=0.63, p=0.002). We conclude that the morning cortisol response to awakening can provide important information on the (re)activity of the HPA axis in addition to more 'traditional' methods like hCRH or Synacthen challenge tests. The sensitivity/capacity of the adrenal cortex appears to play a crucial role for the magnitude of cortisol responses observed after awakening.

Adrenal Cortex↗
PubMed1999

Actions of dehydroepiandrosterone and its sulfate in the central nervous system: effects on cognition and emotion in animals and humans.

Dehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, exert multiple effects in the rodent central nervous system (CNS). Most of them seem to be mediated through their non-genomic action on several neurotransmitter receptors. DHEA(S) increases neuronal excitability, enhances neuronal plasticity and also has neuroprotective properties. In line with these observations DHEA(S) treatment in rodents enhances memory in several paradigms. Even more studies show antiamnestic effects of the steroids. However, DHEA(S) has also anxiolytic and anti-aggressive properties. In humans cross-sectional and longitudinal studies suggest that DHEAS might be associated with global measures of well-being and functioning; however, a relationship with cognition could not be detected to date. Moreover, studies investigating DHEAS levels in neurodegenerative diseases have produced conflicting results. Experimental studies in elderly humans have revealed preliminary evidence for mood enhancing and antidepressant effects of DHEA treatment, while positive effects on measures of memory and attention could not be found. However, electrophysiological studies demonstrated that DHEA treatment has effects on the human CNS. Several reasons for the discrepancy between data obtained in rodents and humans are discussed and research perspectives are outlined which might help to improve interpretation of results obtained in the two species.

Aged↗
PubMed1999

Two weeks of transdermal estradiol treatment in postmenopausal elderly women and its effect on memory and mood: verbal memory changes are associated with the treatment induced estradiol levels.

The present randomized double blind study investigated the effects of a 2 week transdermal estradiol treatment on memory performance in 38 healthy elderly women. Cognitive performance was tested at baseline and after 2 weeks of estradiol or placebo treatment using verbal, semantic, and spatial memory tests as well as a mental rotation task and the Stroop. Initial results showed no differences after treatment between placebo or estradiol treated subjects. However, within treatment group analysis revealed that estradiol treated subjects who reached higher estradiol levels (larger than 29 pg/ml) performed significantly better after treatment in the delayed recall of the paired associate test (verbal memory) than subjects who reached lower estradiol levels (P < 0.05). A nonsignificant trend was observed for the immediate recall condition (P < 0.10). These findings were strengthened by correlations between treatment-induced estradiol levels and changes in verbal memory performance. In addition, there was an association between estradiol levels and mood changes. However mood changes were not significantly associated with changes in verbal memory performance (P > 0.20). The present study supports the idea that estradiol replacement has specific effects on verbal memory in healthy postmenopausal women, with delayed recall being more affected. It suggests that these effects can occur relatively rapidly, and that there may be a dose response relationship of estradiol to memory enhancement. Furthermore, the fact that these results were obtained in women who had been menopausal for an average of 17 years before entering the study indicates that the brain maintains a sensitivity for estrogens even after years of low estradiol plasma concentrations.

Administration, Cutaneous↗
PubMed1999

Psychological and endocrine responses to psychosocial stress and dexamethasone/corticotropin-releasing hormone in healthy postmenopausal women and young controls: the impact of age and a two-week estradiol treatment.

In this placebo-controlled double-blind study, psychological and endocrine stress responses were investigated in healthy postmenopausal placebo-treated women (n = 15; 60-75 years; placebo via transdermal patches), healthy postmenopausal estradiol-treated women (n = 13; 60-79 years; 0.1 mg 17beta-estradiol daily via transdermal patches) and young controls (n = 15; 20-31 years; untreated). The aged subjects received estradiol or placebo treatment for 14 days. All subjects were then exposed to the 'Trier Social Stress Test' (TSST) and the dexamethasone (Dex)-human corticotropin-releasing hormone (hCRH) test (100 microgram hCRH after premedication with 1.5 mg Dex). Psychological parameters including perceived stressfulness, mood and subjective well-being were measured by visual analog scales, a mood questionnaire and a mood diary, respectively. Results show that the TSST induced significant increases in adrenocorticotropin (ACTH), free salivary cortisol, total plasma cortisol and heart rates (all p < 0.0001). Regardless of age, comparable hormonal response patterns were observed in the TSST as indicated by similar peak levels and recovery phases. Visual analog scales confirmed that the same amount of stress was experienced by young and elderly subjects. In both age groups, hCRH injection after Dex premedication provoked significant increases in ACTH, free salivary cortisol and total plasma cortisol (all p < 0.0001). In contrast to the psychosocial stressor, elderly women were found to respond with a markedly enhanced cortisol response compared to young controls in the Dex-CRH test (p < 0.025). Additional investigation of morning cortisol profiles could not reveal any age-related differences in basal hypothalamus-pituitary-adrenal (HPA) axis activity. Following estradiol treatment, estradiol levels significantly increased only in substituted postmenopausal women (p < 0.001) reaching concentrations typically found in younger women during the follicular phase of the menstrual cycle. Corticosteroid-binding globulin levels did not differ significantly between groups. When confronted with the TSST, no response differences emerged between the three groups. However, estradiol treatment appeared to blunt the total plasma cortisol response in the Dex-CRH test, resulting in smaller increases in untreated premenopausal women and estradiol-treated postmenopausal women compared to placebo-treated postmenopausal women (p < 0.02). In sum, no response differences were observed after confrontation with a psychosocial stress test in our sample of healthy elderly subjects. As shown with the Dex-CRH test, our data suggest that the negative feedback of the HPA axis in elderly women is altered. Moreover, the current data suggest that estradiol replacement may modulate HPA feedback sensitivity in humans.

Adrenocorticotropic Hormone↗
PubMed1999

Evaluation of hypothalamo-pituitary-adrenal activity in the tree shrew (Tupaia belangeri) via salivary cortisol measurement.

Saliva sampling is frequently used in humans for adrenal glucocorticoid hormone analysis because of advantages such as non-invasiveness, the ease of collection, and storing of the samples. To transfer this advantageous method to laboratory mammals, potentially confounding factors such as stressful handling procedures have to be excluded. In the present study we established a method for collecting saliva for cortisol measurement in freely moving adult male tree shrews (Tupaia belangeri). The practicability of the procedure was demonstrated (i) by stress-induced changes in cortisol levels revealing a significant increase during the stress phase (control = 0.91 nmol/l vs stress = 1.71 nmol/l), and (ii) by reporting no significant differences in salivary cortisol levels before and after performance of a learning task. The present study emphasizes the use of salivary cortisol analysis especially for monitoring acute changes in the hypothalamo-pituitary-adrenal axis activity in male tree shrews.

Adrenal Glands↗
PubMed1999

No evidence for a close relationship between personality traits and circadian cortisol rhythm or a single cortisol stress response.

Personality traits measured with the Eysenck Personality Questionnaire-Revised did not show associations with basal or stimulated concentrations of cortisol in a sample of 81 subjects. Cortisol responses to a single exposure to psychosocial stress as well as circadian salivary-free cortisol patterns did not distinguish between subjects with high or low scores on Extraversion, Neuroticism, or Psychoticism, respectively.

Adrenocorticotropic Hormone↗
PubMed1998

A longitudinal study of work load and variations in psychological well-being, cortisol, smoking, and alcohol consumption.

The effects of variations in work load (indexed by paid work hours) on psychological well-being, cortisol, smoking, and alcohol consumption were examined in a sample of 71 workers (44 women, 27 men) in the retail industry. Measures were obtained on four occasions over a six-month period, and assessments were ranked individually according to hours of work over the past seven days. Job strain (demand/control) and job social support were evaluated as potential moderators of responses. Paid work hours ranged from a mean of 32.6 to 48.0 hours per week, and ratings of work-home conflict and perceived stress varied across assessments. Salivary cortisol was inversely associated with job strain and did not vary across sessions. Female but not male smokers consumed more cigarettes during periods of long work hours, and self-reported smoking and cotinine concentrations were greater among smokers with higher nicotine dependency scores. Men but not women with poor social supports consumed more alcohol as work hours lengthened. These data indicate that health behaviors are affected only to a limited extent by variations in work load. Results are discussed in the context of adaptation to work and the pathways linking stressful experience with health risk.

Adult↗
PubMed1998

Stressors and mood measured on a momentary basis are associated with salivary cortisol secretion.

Effects of past, current, and anticipated naturalistic daily stressors and of affect on salivary cortisol levels were examined. Participants (120) reported on stressors and affect 6 x /day in response to a preprogrammed wristwatch. Twenty min after each assessment they took a sample of saliva for cortisol analysis. Both the experience of a current stressor and anticipating a stressor were associated with increased salivary cortisol levels. Average increases in cortisol were relatively low, but inter-individual variability in this response existed. Stressors also were associated with lower positive affect and higher negative affect. Negative affect was associated with higher cortisol levels and positive affect was associated with lower cortisol levels. Daily stressors were not significant predictors of cortisol secretion when affect was controlled. Momentary assessment of daily stressors and of salivary cortisol proved to be a useful tool for examining psychoendocrinological processes in the natural environment.

Adult↗
PubMed1998

Opposing effects of DHEA replacement in elderly subjects on declarative memory and attention after exposure to a laboratory stressor.

Aging is accompanied by a continuous decline of the adrenal steroid hormone DHEA and its ester DHEAS. Results from studies in rodents have demonstrated that DHEA(S) administration can enhance memory in several test paradigms. However studies from this laboratory did not find positive effects of DHEA treatment on cognitive performance in young and elderly humans. With respect to a possible mechanism of DHEA activity, effects on several neurotransmitter receptors as well as a possible antiglucocorticoid action are discussed. For high levels of glucocorticoids, a disruptive effect on hippocampal mediated memory is documented in rodents and humans. Therefore it was speculated that, if an antiglucocorticoid action of DHEA would underlie the observed beneficial effects of DHEA on memory, these effects might only be detectable if subjects are stressed (and therefore have high cortisol levels). To test this hypothesis 75 elderly women and men participated in a placebo controlled experiment. Subjects took DHEA (50 mg/day) or placebo for 2 weeks (double blind). Thereafter they participated in a standardized psychosocial laboratory stressor (Trier Social Stress Test; TSST). Before and after stress exposure subjects completed two declarative memory tests (visual-verbal and spatial) as well as one attention test. In addition recall of visual material learned before stress was assessed after stress. Baseline DHEAS levels were significantly lower compared with young adults. DHEA replacement increased DHEAS levels into ranges found in young subjects. DHEA-substituted subjects showed a trend towards a larger cortisol stress response. In the visual memory test subjects under DHEA recalled less items after stress which they had learned before stress. In the attention test however subjects under DHEA performed better than subjects from the placebo group after stress. No interaction between stress and DHEA was found for the spatial memory task. The effects of DHEA substitution on memory and attention after stress exposure seem to be heterogenous. While recall of previously learned material seems to be impaired, attention is enhanced. These results do not support the idea of a direct antiglucocorticoid or anti-stress effect of DHEA on hippocampal mediated memory functions.

Aged↗
PubMed1998

Life events and social support as moderators of individual differences in cardiovascular and cortisol reactivity.

Whether prior stress increases acute stress reactivity is unresolved. The impact of life events (within the past 12 months) and social support on cardiovascular responses was investigated in 90 young male firefighters. Cardiovascular and cortisol measures were collected across baseline, arithmetic, and speech tasks; intertask recovery; and three recovery trials. Reactivity differences were not independently associated with life events. High social support was associated with greater arithmetic cardiovascular reactivity and faster recovery. Combined life events and social support grouping showed that effects of support were accentuated when event frequency was high, suggesting that life events and support interacted to sensitize future stressor responses. Support may promote the alerting response mobilization but prevent chronic allostatic load by enhancing recovery.

Adult↗
PubMed1998

Effects of dehydroepiandrosterone replacement in elderly men on event-related potentials, memory, and well-being.

BACKGROUND: In humans, concentrations of the adrenal steroid hormone dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) decline with age. Results from studies in rodents have suggested that DHEA administration can improve memory performance as well as neuronal plasticity. However, a first study from our laboratory could not demonstrate beneficial effects of DHEA substitution on cognitive performance and well-being in elderly subjects. To further evaluate whether DHEA replacement has effects on the central nervous system, an experiment using event-related potentials (ERPs) was conducted. METHODS: In this placebo-controlled crossover study, 17 elderly men (mean age, 71.1 +/- 1.7 yr; range 59-81 yr) took placebo or DHEA (50 mg/day) for 2 weeks (double blind). After each treatment period subjects participated in an auditory oddball paradigm with three oddball blocks. In the first two blocks subjects had to count the rare tone silently, whereas, in the third block they had to press a button. In addition, memory tests assessing visual, spatial, and semantic memory as well as questionnaires on psychological and physical well-being were presented. RESULTS: Baseline DHEAS levels were lower compared with young adults. After 2-week DHEA replacement, DHEAS levels rose 5-fold to levels observed in young men. DHEA substitution modulated the P3 component of the ERPs, which reflects information updating in short-term memory. P3 amplitude was increased after DHEA administration, and only selectively in the second oddball block. DHEA did not influence P3 latency. Moreover, DHEA did not enhance memory or mood. CONCLUSIONS: A 2-week DHEA replacement in elderly men results in changes in electrophysiological indices of central nervous system stimulus processing if the task is performed repeatedly. However, these effects do not appear to be strong enough to improve memory or mood.

Aged↗
PubMed1998

Sex differences in endocrine and psychological responses to psychosocial stress in healthy elderly subjects and the impact of a 2-week dehydroepiandrosterone treatment.

Evidence from animal as well as human studies has suggested that significant sex differences exist in hypothalamus-pituitary-adrenal axis (HPA) activity. As gonadal steroids could be important modulators of HPA sex differences, stress responses were investigated in subjects of advanced age after dehydroepiandrosterone (DHEA) or placebo treatment. After a 2-week treatment with 50 mg DHEA daily or placebo, 75 men and women (mean age, 67.6 yr) were exposed to the Trier Social Stress Test (TSST). The TSST is a brief psychosocial stress that consists of a free speech and mental arithmetic task in front of an audience. The results show that the TSST induced significant increases in ACTH, salivary free cortisol, total plasma cortisol, norepinephrine, and heart rates (all P < 0.0001) as well as decreased positive affect in the elderly (P = 0.0009). Men showed larger stress responses in ACTH (P = 0.004), salivary free cortisol (P = 0.044), and plasma total cortisol (P = 0.076) compared to women. No sex differences were observed in norepinephrine, epinephrine, or heart rate responses. In contrast to ACTH and cortisol response differences, women reported that they were significantly more stressed by the TSST than men (P = 0.0051). Women treated with DHEA showed ACTH stress responses similar to those of men, but significantly enhanced compared to those of women taking placebos (P < 0.009). No other stress response differences emerged between DHEA and placebo groups. Finally, DHEA treatment did not result in an improvement of subjective well-being. We conclude that elderly men show larger HPA responses than women to psychosocial stress, as studied in the TSST. Estrogen effects on hypothalamic CRF-producing neurons might be responsible for these sex differences.

Adrenocorticotropic Hormone↗
PubMed1997

Free cortisol levels after awakening: a reliable biological marker for the assessment of adrenocortical activity.

In three independent studies, free cortisol levels after morning awakening were repeatedly measured in children, adults and elderly subjects (total n=152). Cortisol was assessed by sampling saliva at 10 or 15 minute intervals for 30-60 minutes, beginning at the time of awakening for two days (Study 1 and 2) or one (Study 3) day, respectively. In all three studies, free cortisol levels increased by 50-75% within the first 30 minutes after awakening in both sexes on all days. Premenopausal women consistently showed a stronger increase with a delayed peak after awakening compared to men on all days. In Study 2, there was a tendency for lower early morning free cortisol levels for women taking oral contraceptives (p=.10). Stability of the area under the curve (AUC) of the early morning free cortisol levels over the three (Study 1 and 2) or two (Study 3) days ranged between r=.39 and r=.67 (p<.001). Neither age, weight, nor smoking showed an effect on baseline or peak cortisol levels. Sleep duration, time of awakening and alcohol consumption also appeared to be unrelated to early morning free cortisol levels. From these data we conclude that in contrast to single assessments at fixed times, early morning cortisol levels can be a reliable biological marker for the individual's adrenocortical activity when measured repeatedly with strict reference to the time of awakening.

Adrenal Cortex↗
PubMed1997

Adrenocortical responses to repeated parachute jumping and subsequent h-CRH challenge in inexperienced healthy subjects.

The present study examined the adrenocortical response to 3 consecutive parachute jumps and a poststress h-CRH challenge. Fifteen participants in a parachute-jumping course took saliva samples for later cortisol analysis every 20 min throughout the day, when they accomplished their very first 3 parachute jumps and throughout a control day. The effects of an h-CRH challenge on salivary cortisol were assessed in the evening of the jumping day and on a control day. Parachute jumping induced 3 distinct highly significant adrenocortical responses. The respective cortisol increases for the first, second, and third jump were 39.4 +/- 26.5 nmol/1, 31.4 +/- 21.4 nmol/l, and 16.5 +/- 11.9 nmol/l. Cortisol responses to the first and second jump did not differ but the response to the third jump was significantly reduced [t(13) = 3.11; p = 0.008]. Two groups of subjects were identified, "decreasers," whose response decreased from one to the other jump, and "increasers," whose response remained unchanged or increased. The magnitude of the preceding cortisol response of decreasers exceeded that of increasers significantly by about 30 nmol. The mean adrenocortical effects of the poststress h-CRH challenge and the time-matched challenge on a control day did not differ although, in 4 subjects, the poststress adrenocortical response to h-CRH was completely suppressed.

Adrenal Glands↗
PubMed1997

Individual differences in the diurnal cycle of cortisol.

This study investigated individual differences in the diurnal cycle of cortisol and explored their relation to several psychosocial variables and to upper-respiratory symptoms. Cortisol and daily experience were assessed for 2 days in 109 healthy employed and unemployed community residents (mean age = 36.4 +/- 12.1, 69% female); self-report upper respiratory illness (URI) symptoms were assessed for an additional 10 days. Fifty-six (51%) participants showed typical declines in cortisol during both days, 19 (17%) showed no significant diurnal pattern on both days, and 34 (31%) showed different diurnal patterns on the 2 days. Individuals with no cycles did not differ from those with normal or inconsistent cycles on demographic factors, baseline psychological measures, health behaviors, or daily experiences over the two assessment days. Individuals without cortisol cycles, however, reported fewer URI symptoms than the remaining subjects. That 17% of our sample did not exhibit diurnal cycles of cortisol was surprising, given established views of normal endocrine function. Although average daily level of cortisol is related to a number of psychosocial and psychiatric factors (e.g. stress and depression), pattern of diurnal cycle was not related to any demographic or psychosocial measures in this study. The finding that flat cycles were related to fewer reports of URI symptoms suggests that perturbations in cycle may be related to processes associated with symptom susceptibility or symptom expression.

Adult↗