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Biomedical subjects

C Kirschbaum

Publications and source records attributed to C Kirschbaum.

At least 73 records · Page 4Linked to original sources
PubMed1992

Synthesis of a cortisol-biotin conjugate and evaluation as a tracer in an immunoassay for salivary cortisol measurement.

Cortisol 3-(o-carboxymethyl)oxime (C3-CMO) and a commercially available biotin-hydrazide derivative were used to synthesize a C3-CMO-biotin conjugate. C3-CMO was converted into a N-hydroxysuccinimide ester derivative which in a second reaction step was allowed to interact with the hydrazide derivative of biotin. This simple-to-perform synthesis yielded a conjugate suitable for use as a tracer in immunoassays for cortisol measurement. Employing biotin as the primary probe in a competitive solid phase immunoassay allows for variable end point determination by means of commercially available labeled avidin or streptavidin derivatives. Streptavidin-Europium was used in conjunction with the DELFIA-system for time-resolved fluorometric end point measurement (TR-FIA) throughout the study. In addition, colorimetric end point determination (ELISA) using streptavidin-alkaline phosphatase as a secondary probe was established and evaluated. Both forms of this non-isotopic assay showed excellent correlation with a commercially available radioimmunoassay adapted for salivary cortisol measurement. The lower detection limit was 0.43 nM for a 50 microliters salivary sample. The intra-assay coefficient of variation was 6.7, 4.7 and 4.0% at cortisol concentrations of 2.2, 5.5 and 13.2 nM, respectively (n = 37), and the corresponding inter-assay coefficients of variation were 9.0, 8.6 and 7.1% (n = 50). The competitive immunoassay requires 1.5 h incubation time and shows robust and reproducible performance. The C3-CMO-biotin conjugate allows for sensitive and flexible end point determination of salivary cortisol levels in immunoassays.

Biotin↗
PubMed1992

Conditioning of drug-induced immunomodulation in human volunteers: a European collaborative study.

Although several studies on conditioning of the immune system in animals have been published, no comparable data on human research have been available in the past. The present paper presents results of conditioning studies in volunteers performed in two research centres, namely the University of Trier (Germany) and the University of Utrecht (The Netherlands). After administration of a neutral stimulus (conditioned stimulus: CS), subjects were injected with epinephrine (unconditioned stimulus) for three or four days (depending on study). Subcutaneous injection of epinephrine caused a rapid enhancement of the activity of natural killer cells (NKCA) in venous blood, which was chosen as the unconditioned response. On the test trial, when saline instead of epinephrine was injected, the Trier group found a conditional enhancement of NKCA. No changes in NKCA were found in the control subjects, who received saline injections on all days along with the CS. The Utrecht group tried to replicate these results using a slightly different design. After obtaining non-confirmative results, the Utrecht experimenters tried to parallel the experimental settings of the Trier group as closely as possible. However, once again they failed to replicate the results of the Trier group. Possible reasons for the different results obtained in the two research groups are discussed.

Adult↗
PubMed1992

Heritability of cortisol responses to human corticotropin-releasing hormone, ergometry, and psychological stress in humans.

The present study investigated cortisol responses to three different stimulation procedures, with a focus on the contribution of genetic factors. Thirteen monozygotic (MZ) twin pairs and 11 dizygotic (DZ) twin pairs performed bicycle ergometry until exhaustion and were exposed to the psychological stress of public speaking and mental arithmetic in front of an audience. Furthermore, 9 MZ pairs and 10 DZ pairs were injected with 100 micrograms synthetic human CRH (hCRH). The adrenocortical response to these challenges was monitored by determination of cortisol in saliva. Significant intraindividual stability of baseline cortisol levels was found in females, but was less in males. Maximum cortisol responses to all three stimulation procedures were significantly intercorrelated in males, but in females only the cortisol responses to hCRH and ergometer exercise showed a significant correlation. While a decided influence of genetic factors was observed for all three baseline cortisol levels as well as for the response to hCRH, heredity appeared to be play a minor role in the adrenocortical response to psychological stress. Cortisol changes after bicycle ergometry revealed no impact of genetic factors on the secretion of cortisol in response to strenuous physical exercise.

Adolescent↗
PubMed1992

Family violence: a letter to my doctor.

The epidemic of family violence in America is widespread, deadly and complex. Even the very young, the very old and pregnant women may be safer on the streets than in there own homes, according to a recent article in the AM News. The cost to our society is staggering. And you, as physicians, are on the front lines, daily confronting the effects of this national crisis. Approximately every third patient you see is a victim of family violence. Your patients' bruises, fractures and other injuries are often symptoms of a far more sinister disease. The patient needs your help. As doctors, you are being asked to treat not just the symptoms but also the underlying cause--to look below the surface to the illness beneath. As healthcare professionals you are being asked to take the lead in helping society eradicate this devastating epidemic and restore the health of our families through these individual lives. In a letter to you, her trusted doctor, the following profiles a victim of abuse.

Female↗
PubMed1991

Developmental and personality correlates of adrenocortical activity as indexed by salivary cortisol: observations in the age range of 35 to 65 years.

Unstimulated salivary cortisol concentrations were measured in 767 adults aged 35-65 yr over the course of one day. Interindividual differences in early morning cortisol concentrations showed consistent and significant relationships with demographic and psychological variables. Socioeconomic status was positively associated with cortisol levels. Relationships of cortisol levels with age were moderated by gender: for women, a negative regression of cortisol level on age was observed while no significant age effects were obtained for men. In bivariate and multivariate regression analyses, a positive association between cortisol levels and indicators of successful development and personal well-being was observed; these relationships were more pronounced for the male sample. Intradyadic correlations further revealed a slight but significant association of morning cortisol levels within married couples. The findings are discussed with respect to mediating developmental mechanisms and pathophysiological implications.

Adaptation, Psychological↗
PubMed1990

Postpartum blues: salivary cortisol and psychological factors.

The relationships between several psychological variables and salivary cortisol levels were investigated in 70 young mothers throughout the first five days following the delivery of a healthy baby. We hypothesized that postpartum blues is associated with ineffective coping strategies, high anxiety levels, and elevated salivary cortisol concentrations. Data analysis revealed that symptoms of postpartum blues occurred more frequently in women who reported high levels of trait-anxiety, passive coping strategies, marital dissatisfaction, or acceptance of their role as a mother. These women had elevated morning levels of cortisol on those days on which the symptoms appeared in contrast to those days without symptoms as well as in contrast to those women who did not experience postpartum blues.

Adaptation, Psychological↗
PubMed1990

Cortisol and behavior: 2. Application of a latent state-trait model to salivary cortisol.

In two studies we applied a new stochastic model for the measurement of latent states and traits to salivary cortisol in healthy subjects. Data were analyzed by Linear Structural Relations (LISREL). In the first study, 48 students collected saliva samples on two occasions at 1300h with an interval of six weeks between occasions. Salivary cortisol levels were found to be mainly influenced by situational and/or interactional effects, which determined approximately 75% of the total variance of the hormone data, while only approximately 21% were determined by the latent trait. Measurement unreliability was found to be approximately 4%. In the second study, 54 young mothers collected saliva at 0800h, 1500h, and 2000h for three consecutive days, starting on the second day after delivery of a healthy baby. Early morning salivary cortisol showed high consistency across the three days. Approximately 60% of the total variance in the early morning cortisol samples was determined by the latent trait. For the 1500h and 2000h samples, however, the corresponding proportions of variances amounted only to 33% and 28%, respectively. These results appear to reflect the absence of a clear-cut circadian rhythm in some of the women on the second day after delivery.

Adult↗
PubMed1989

Cortisol and behavior: 1. Adaptation of a radioimmunoassay kit for reliable and inexpensive salivary cortisol determination.

We adapted a commercial serum cortisol radioimmunoassay (RIA) kit for use with saliva specimen. Using 50 microliters sample volume, the lower sensitivity was found to be 0.02 microgram/dl with intraassay variation coefficients between 5.4 and 8.9% at different concentrations. The 50% intercept was either 0.5 or 0.26 microgram/dl (50 or 100 microliters standard/sample volume). Fifty-four early morning samples from healthy adults showed absolute concentrations which are closely comparable to respective data from other laboratories. A comparison of 35 saliva samples which were each assayed with the adapted RIA as well as with three other commercial kits revealed high correlations between these assays (r = .94 to r = .97). Data on salivary cortisol responses to CRH stimulation and dexamethasone suppression in healthy subjects further the validity of the assay results. The most important contribution of this assay modification, however, is thought to be its impact on analysis costs: The protocol presented in this paper allows for reliable salivary cortisol measures with a reduction of costs for analytical material to 25% compared to serum determinations.

Corticotropin-Releasing Hormone↗
PubMed1989

Salivary cortisol in psychobiological research: an overview.

The measurement of cortisol in saliva provides the basic scientist as well as the clinician with a reliable tool for investigations of hypothalamus-pituitary-adrenal axis activity. Since saliva samples can be obtained stress-free and independent from medically trained personnel this method may be well suited for use in psychobiological studies. This overview intends to give a comprehensive introduction to the method of salivary cortisol assessment and to briefly discuss its application in different scientific disciplines.

Animals↗
PubMedDate not supplied

Conditioned increase of natural killer cell activity (NKCA) in humans.

Cumulating evidence suggests that immune parameters can be modified by behavioral conditioning processes in animals. The present results suggest that this also holds true for a human immune parameter. Healthy subjects were exposed to a conditioning procedure in which a neutral sherbet sweet (conditioned stimulus) was repeatedly paired with a subcutaneous injection of 0.2 mg epinephrine (unconditioned stimulus). After epinephrine administration an increase of natural killer (NK) cell activity could be observed (unconditioned response). On the conditioning test day the conditioned group showed increased NK cell activity after reexposure of the sherbet sweet combined with saline injection. No increase was found in control groups that previously received the sherbet sweet in combination with saline (saline control) or with epinephrine in an unpaired manner (unpaired control). This study supports previous findings of conditioned modulation of immune responses and represents a model to investigate conditioning processes of a human immune function.

Adult↗
PubMedDate not supplied

Consistent sex differences in cortisol responses to psychological stress.

In four independent studies, sex differences in cortisol responses to psychological stress were investigated in healthy adolescents and adults (total n = 153). Public speaking and mental arithmetic in front of an audience (Studies 1-3) reliably induced increases in free cortisol levels in both sexes with 2- to 4-fold increases above baseline levels. Mean cortisol responses were 1.5- to 2-fold higher in men compared with women. In Study 3, cortisol profiles were additionally investigated after human corticotropin-releasing hormone (h-CRH) and bicycle ergometry until exhaustion. Here, both sexes showed very similar adrenocortical responses. Furthermore, men showed elevated cortisol levels in anticipation of the psychological stress situation without actually having to perform the tasks (Study 4). Under this condition cortisol concentration was unchanged or decreased in women. From these data we conclude that the observed sex difference does not reflect an overall lower responsiveness of the female adrenal cortex. Although these studies do not provide conclusive data, we suggest sex differences in cognitive and/or emotional responses to distressing psychosocial situations which in turn may influence cortisol secretion.

Adaptation, Psychological↗
PubMedDate not supplied

Sex-specific effects of social support on cortisol and subjective responses to acute psychological stress.

The effects of short-term social support on cortisol levels and subjective responses to acute psychological stress were investigated in healthy adults (total N = 66). In anticipation of a public-speaking task in front of an audience, subjects received either no social support ("no support") or social support from an opposite-sex stranger ("stranger") or from their boyfriend or girlfriend ("partner"). Support providers were instructed to enact both instrumental and emotional support during the 10-minute anticipation period. The results obtained suggest sex-specific effects of social support. Although men in the partner support condition showed significant attenuation of cortisol responses compared with unsupported and stranger-supported men, women showed no response decrement under stranger support. In contrast to men, women showed a tendency toward increased cortisol responses when supported by their boyfriends. The endocrine response differences between male and female subjects were unrelated to questionnaire-derived psychological variables. No sex and group differences in perceived stress, mood changes, or social desirability were observed. Although the overall level of subjective well-being throughout the experiment was elevated in the partner support condition, no sex or group differences were observed in perceived stress, well-being changes, and social desirability. Opposite to their cortisol responses, women rated both stranger and partner support attempts more favorably than did men. No significant correlations were observed between the perceived stressfulness of the situation, mood changes, and cortisol responses. These results provide preliminary evidence for sex-specific patterns of social support efficacy to acute psychological stress with respect to adrenocortical responses.

Adaptation, Psychological↗
PubMedDate not supplied

Effect of chronic stress associated with unemployment on salivary cortisol: overall cortisol levels, diurnal rhythm, and acute stress reactivity.

This study examined the effect of chronic stress associated with unemployment on the magnitude of salivary cortisol excretion, on the diurnal rhythm of cortisol, and on cortisol reactivity to acute naturalistic stressors using Experience Sampling Methodology (ESM). Employed (N = 60) and unemployed (N = 60) subjects were studied for 2 days. Subjects were beeped 6 times per day by a preprogrammed wristwatch to assess acute stressors; 25 minutes after each ESM-beep, subjects were beeped a second time for saliva samples. The groups did not differ in their overall cortisol excretion or in cortisol reactivity to acute daily stressors. Compared to employed subjects, unemployed subjects had a diurnal pattern of cortisol excretion with relatively higher morning and lower evening levels. Subjects' daily activities and their locations were associated with diurnal rhythm differences.

Adult↗
PubMedDate not supplied

Persistent high cortisol responses to repeated psychological stress in a subpopulation of healthy men.

The present study tested the hypothesis that some subjects may not readily show habituation of adrenocortical stress responses to repeated psychological stress. Twenty healthy male subjects were each exposed five times to the same, brief psychosocial stressor (public speaking and mental arithmetic in front of an audience) with one stress session per day. Salivary cortisol levels were assessed as an index of adrenocortical stress responses. For the total group, cortisol levels were significantly elevated on each of the 5 days. The mean response decreased from day 1 to day 2; however, no further attenuation could be observed on the remaining days. Cluster analysis revealed two groups of subjects who showed completely different response kinetics. In the first group (N = 13), termed "low responders," cortisol levels were elevated on day 1 only. Day 2 to 5 cortisol levels were unaltered. In contrast, subjects in the second group ("high responders") displayed large increases to each of the five experimental treatments. This group had no significant response decrement from day 1 to day 2 to 4 and only a marginal response difference between day 1 and day 5. Discriminant analysis revealed that a combination of five personality scales plus the scores on a symptoms checklist significantly discriminated between high and low responders. With this discriminant function, all 20 subjects were correctly classified to the two groups. These results are discussed with a focus on the possible impact of adrenocortical response types on health and disease.

Adult↗
PubMedDate not supplied

Attenuated free cortisol response to psychosocial stress in children with atopic dermatitis.

OBJECTIVE: Atopic dermatitis (AD) is an inflammatory skin disease characterized by a hyperactivity of the humoral immune system with an onset in infancy or early childhood. Although most of the research has focused on the pathophysiological role of the immune system in AD, the impact of endocrine signals in the pathology of AD has received only little attention. However, because the endocrine system may play a regulatory role in immune functioning, it might be of major interest to study endocrine reactivity in AD patients. The present two-part study investigated the relationship between adrenocortical stress response, heart rate response, and psychological parameters in children with AD. METHOD AND RESULTS: In Study 1, a protocol for induction of psychosocial stress in children aged 8 to 14 years was evaluated. Healthy children (N = 16) were exposed to the Trier Social Stress Test for Children (TSST-C) that mainly consists of public speaking and mental arithmetic tasks in front of an audience. Salivary cortisol was measured 35, 15, and 1 minute before as well as 1, 10, 20, and 30 minutes after the stress; heart rate was monitored continuously. Results showed that the protocol induced a highly significant increase in free cortisol response (p < .001) and heart rate (p < .001). In Study 2, the TSST-C was applied to AD children (N = 15) and age- and sex-matched healthy controls (N = 15). All patients were in remission and medication-free for at least 3 weeks. Again, the stress test induced significant increases in cortisol and heart rate. However, the AD children showed a significantly blunted cortisol response to the stressor compared with the control group (p < .05). Heart rate responses were similar in both experimental groups. Neither subjective stress ratings nor personality traits were related to the blunted cortisol response. CONCLUSIONS: These findings suggest that the adrenocortical response to stress is attenuated in atopic children. A hyporesponsive hypothalamus-pituitary-adrenal (HPA) axis might explain in part the stress-induced eruptions of AD symptoms.

Adolescent↗
PubMedDate not supplied

Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis.

OBJECTIVE: Results from animal and human studies suggest that disregulations of the hypothalamus-pituitary-adrenal (HPA) axis are involved in several behavioral, circulatory, endocrine, and immune disorders with clear-cut gender differences in disease prevalence. The aim of the present study was to investigate sex-specific HPA response patterns with a focus on the contribution of gonadal steroids as possible mediators. METHODS: A total of 81 healthy adults were investigated in the present study. Twenty men, 19 women in the follicular phase of the menstrual cycle, 21 women in the luteal phase, and 21 women using oral contraceptives (OC) were exposed to a brief psychosocial stress test (Trier Social Stress Test; TSST) and injected with 0.25 mg ACTH1-24 on consecutive days. Basal HPA activity was investigated by repeatedly measuring cortisol levels immediately after awakening, as well as in 30-minute intervals from 9:00 AM to 9:00 PM. Additionally, questionnaires were used to assess psychological state and trait parameters. RESULTS: Results show that the TSST induced significant increases in ACTH, salivary-free cortisol, total plasma cortisol, and heart rates, as well as increased wakefulness and reduced calmness in the total group. Significant group differences emerged for ACTH and salivary-free cortisol stress responses: Although men showed higher ACTH responses to the TSST compared with each of the three groups of women, salivary cortisol responses showed the following response pattern: Luteal = Men > Follicular = OC. The salivary cortisol responses to ACTH1-24 showed a similar response pattern: Luteal > Men > Follicular > OC. In contrast, total blood cortisol levels did not reveal any group difference between sexes or follicular versus luteal phase in either test. Although a similar salivary-free cortisol increase after awakening was found in the four groups, the circadian cortisol profile was significantly different throughout the first 4 hours of sampling. Questionnaire-derived psychological variables, as measured in the present study, could not explain the observed results. CONCLUSIONS: We conclude that gender, menstrual cycle phase, and OC use exert important effects on HPA responsiveness to psychosocial stress in healthy subjects. Although men seem to have a stronger hypothalamic drive in response to stressful stimulation than women, differences in salivary-free cortisol levels, at least in part, may be explained by estradiol-induced changes in corticosteroid-binding protein levels. ACTH and cortisol secretion is not affected by OC use per se but the amount of bioavailable unbound cortisol ("free") is greatly reduced in this group of women after stimulation. Inasmuch as none of these differences between the study groups emerged in total blood cortisol levels, we strongly advocate for the simultaneous measurement of free and total cortisol levels in future studies on HPA functioning.

Adolescent↗
PubMedDate not supplied

Burnout, perceived stress, and cortisol responses to awakening.

OBJECTIVE: The effects of burnout and perceived stress on early morning free cortisol levels after awakening were investigated in a group of teachers. Previous studies revealed that cortisol levels show a significant increase after awakening, with high intraindividual stability. METHODS: Sixty-six teachers from local public schools (42 women and 24 men, mean age 42+/-5 years) were asked to sample saliva for cortisol analysis on 3 consecutive days. On each day, cortisol levels were measured at the time of awakening and 15, 30, and 60 minutes thereafter. On the night before the third day, subjects took 0.5 mg dexamethasone orally for testing glucocorticoid feedback inhibition. Burnout and perceived stress were measured by three different questionnaires. RESULTS: Perceived stress correlated with increases of cortisol levels during the first hour after awakening after dexamethasone pretreatment. In addition, teachers scoring high on burnout showed lower overall cortisol secretion on all sampling days, and a higher suppression of cortisol secretion after dexamethasone administration. In the subgroup of teachers with both high levels of perceived stress and high levels of burnout, a lower overall cortisol secretion was observed on the first 2 days, with stronger increases during the first hour after awakening after dexamethasone suppression. This subgroup also showed the lowest self-esteem, the highest external locus of control, and the highest number of somatic complaints. CONCLUSIONS: These results demonstrate differential effects of burnout and perceived stress on hypothalamic-pituitary-adrenal axis regulation.

Adrenocorticotropic Hormone↗