PubMed Health⌕ Search

Biomedical subjects

C Kirschbaum

Publications and source records attributed to C Kirschbaum.

At least 19 recordsLinked to original sources
PubMed2006

Serotonin transporter gene variation impacts innate fear processing: Acoustic startle response and emotional startle.

Anxiety-related behaviors are closely linked to neural circuits relaying fear-specific information to the amygdala. Many of these circuits, like those underlying processing of innate fear, are remarkably well understood. Recent imaging studies have contributed to this knowledge by discriminating more detailed corticoamygdalar associations mediating processing fear and anxiety. However, little is known about the underlying molecular mechanisms. We used the acoustic startle paradigm to investigate the impact of molecular genetic variation of serotonergic function on the acoustic startle response and its fear potentiation. Startle magnitudes to noise bursts as measured with the eye blink response were recorded in 66 healthy volunteers under four conditions: presenting unpleasant and pleasant affective pictures as well as neutral pictures, and presenting the startle stimulus without additional stimuli as a baseline. Subjects were genotyped for functional polymorphism in the transcriptional control region of the serotonin transporter gene (5-hydroxytryptamine transporter gene-linked region: 5-HTTLPR). Analyses of variance revealed a significant effect of 5-HTTLPR on overall startle responses across conditions. Carriers of the short (s) allele exhibited stronger startle responses than l/l homozygotes. However, we could not confirm our hypothesis of enhanced fear potentiation of the startle in s allele carriers. In conclusion, the results provide first evidence that the startle response is sensitive to genetic variation in the serotonin pathway. Despite some issues remaining to be resolved, the startle paradigm may provide a valuable endophenotype of fear processing and underlying serotonergic influences.

Acoustic Stimulation↗
PubMed2005

Impact of experimentally induced serotonin deficiency by tryptophan depletion on saliva cortisol concentrations.

BACKGROUND: Tryptophan depletion (TD) has been shown to induce a transient mood-lowering effect in psychiatric patients and susceptible healthy subjects. We investigated the effects of TD on cortisol secretion in psychiatric patients and healthy subjects based on the hypothesis that the potential mood-lowering effects may be associated with increased activity of the hypothalamic-pituitary-adrenal axis, thus leading to a rise of cortisol secretion. METHODS: After TD at 18.00 h, salivary cortisol was sampled in the evening and on the following morning. The first study was a randomized, placebo-controlled, crossover study in healthy subjects. Two further open trials in patients with obsessive-compulsive disorder (OCD) and primary insomnia compared the effects of TD on cortisol with baseline conditions. RESULTS: In healthy subjects, TD significantly diminished cortisol the next morning compared with placebo. In OCD patients and primary insomniacs, cortisol the morning after TD was lowered compared with baseline. Evening cortisol was not affected by TD in any of the groups. CONCLUSIONS: Contrary to expectation, TD led to a comparable decrease of morning cortisol in all groups investigated. However, these findings are consistent with former studies analyzing the impact of antiserotonergic drugs on cortisol secretion. The results underline that the antiserotonergic effects caused by TD may influence cortisol secretion.

Adult↗
PubMed2004

HPA axis responses to laboratory psychosocial stress in healthy elderly adults, younger adults, and children: impact of age and gender.

Data from five independent studies were reanalyzed in order to investigate the impact of age and gender on HPA axis responses to an acute psychosocial laboratory stress task. The total sample consisted of 102 healthy subjects with 30 older adults (mean age: 67.3 y), 41 young adults (mean age: 23.5 y), and 31 children (mean age: 12.1 y). All participants were exposed to the Trier Social Stress Test (TSST). The stress protocol caused highly significant ACTH and total plasma cortisol responses in older and younger male and female adults (all p<0.0001) as well as salivary free cortisol responses in all six age and gender groups (all p<0.0001). Three-way ANOVAs for repeated measurement were applied to investigate the impact of age and gender on ACTH and cortisol responses. Results showed that the ACTH response to stress was higher in younger adults compared to older adults (main effect: p=0.009, interaction: p=0.06). Post hoc analyses revealed that there was no age effect in the subgroup of women (p=n.s.), while younger men had higher ACTH responses compared to older men (p=0.01). For total plasma cortisol, ANOVA results showed that the pattern of reactivity did not differ between age and gender groups (all interactional effects p=n.s.), although older females had hightened overall cortisol levels compared to the other groups, as proofed in post hoc analyses (all p<0.05). For free salivary cortisol, a significant main effect of gender (p=0.05) and an almost significant three-way-interaction (p=0.09) emerged. Post hoc analyses showed an elevated overall free salivary cortisol response in elderly men compared to elderly women (p=0.006), while no gender differences emerged in neither young adults nor children (both p=n.s.). In sum, the stressor induced significant HPA axis responses in all age and gender groups. The observed ACTH response patterns in young and elderly adults may suggest that a heightened hypothalamic drive in young men decreases with age, resulting in similar ACTH responses in elderly men and women. Alternative interpretations are also discussed. The data also supports the idea of a greater adrenal cortex sensitivity to ACTH signals in young females. Free salivary cortisol responses were elevated in elderly men compared to elderly women, an effect which cannot be explained by gender differences in perceived stress responses to the TSST. It can be speculated if corticosteroid binding globulin (CBG) and/or sex steroids are important modulators of these effects.

Adrenocorticotropic Hormone↗
PubMed2004

Cortisol and memory retrieval in humans: influence of emotional valence.

Glucocorticoids secreted in response to stress modulate memory in animals and humans. Studies in rodents suggest that glucocorticoids enhance memory consolidation but impair delayed retrieval. Similar negative effects on memory retrieval have been reported in humans. The human studies so far have not addressed the issue of emotional valence, which conceivably could modulate the effects of cortisol on retrieval. The present mini-review discusses two recent studies from our laboratories that investigate the influence of emotional valence on the retrieval-impairing effects of cortisol. Both studies observed that cortisol impaired retrieval and that emotional valence influenced these effects. For autobiographical memory the impairing effects were stronger for neutral than for emotional items, whereas for word retrieval the opposite pattern was observed (stronger effects on emotional words). Possible reasons for these results are the different memory domains tested as well as the different sex of the subjects. Future studies will address these issues, which are of relevance for psychiatric disorders such as posttraumatic stress disorder or major depression.

Emotions↗
PubMed2003

Awakening cortisol responses are influenced by health status and awakening time but not by menstrual cycle phase.

Recent evidence suggested that the free cortisol response to awakening is influenced by awakening time in healthy younger adults (Edwards et al., 2001). In order to investigate this association further, 179 community-dwelling subjects of a large age range (4-75 yrs) participated in the present study. The sample consisted of 99 women, 67 men and 13 children. Subjects were instructed to obtain saliva samples directly after awakening as well as 15, 30, 45, and 60 minutes thereafter. A first analysis revealed that salivary cortisol profiles after awakening in healthy subjects differed from profiles in subjects who reported health problems or a chronic disease (p = 0.02) with healthy subjects showing a larger cortisol response. Therefore, only healthy subjects were included in the following analyses. Subjects woke up between 0455 and 1203 h. Time of awakening strongly influenced the course of morning cortisol levels. Cortisol profiles differed significantly between two wake-up groups (p<0.001). Similarly, group differences for cortisol increase (p = 0.03) and area under the curve (p = 0.05) were also significant, with more pronounced responses in early awakeners compared to late awakeners. The findings are discussed with respect to the circadian cortisol rhythm and the effects of light exposure. Age was correlated with the cortisol levels immediately after awakening (r = 0.2, p = 0.04), the area under the cortisol curve ( r = -0.20, p = 0.05), and with time of awakening (r = -0.21, p = 0.04), respectively. No differences were found between males and females, or between profiles obtained during the follicular or luteal menstrual cycle phase. Also, no differences were observed between habitual smokers vs. non-smokers. These data suggest that the morning cortisol response is influenced by the awakening time but not by menstrual cycle phase. Moreover, health status and age appear to have an impact on this marker of adrenocortical activity. Wake-up time, health status and age should therefore be controlled for in future studies measuring cortisol responses to awakening.

Adolescent↗
PubMed2003

Impact of oral contraceptive use on glucocorticoid sensitivity of pro-inflammatory cytokine production after psychosocial stress.

We previously reported that women using oral contraceptives (OC) show blunted free cortisol responses to psychosocial stress compared to medication-free women. Low cortisol responses to stress have been shown to be associated with increased susceptibilities to chronic inflammatory and autoimmune processes in animal models and certain human diseases.To address the question if the blunted free cortisol response of OC users may be compensated at the level of the target tissue, we measured hypothalamus-pituitary-adrenal (HPA) axis activation and glucocorticoid (GC) sensitivity of pro-inflammatory cytokine production after psychosocial stress in 14 women using OC and 11 women in the luteal phase of the menstrual cycle. All subjects were exposed to the psychosocial stress paradigm 'Trier Social Stress Test' (TSST). Free cortisol was measured repeatedly before and after stress. GC sensitivity was assessed by dexamethasone (DEX) inhibition of lipopolysaccharide (LPS) stimulated production of interleukin-6 (IL-6) in whole blood, immediately before, as well as 10 and 60 min after the stress test. As expected, the stress test induced significant increases in free cortisol in luteal phase women, while OC users showed blunted responses (F=3.31;p<0.05). GC sensitivity showed different response patterns; In luteal phase women a slight but not significant decrease was observed throughout the experiment. In contrast, women using OC showed a significant increase in GC sensitivity after stress (F=3.559;p<0.05). These results show, that an increase in GC sensitivity of pro-inflammatory cytokine production may at least in part compensate the low cortisol levels seen in OC users after stress. This could be one mechanism to protect women using OC medication from chronic inflammatory and autoimmune diseases.

Adult↗
PubMed2001

Individual differences in the diurnal cycle of salivary free cortisol: a replication of flattened cycles for some individuals.

Free cortisol measured in saliva has been shown to have the same diurnal rhythm as serum cortisol, one that typically declines rapidly throughout the waking day. A recent study showed that over 15% of a sample of community individuals who were monitored over two days did not show the typical diurnal rhythm. The present study specifically tested the hypothesis that there is significant between-subject variation (individual differences) in diurnal rhythms using multi-level, random regression models. Analyses of participants from four studies were conducted; studies varied in terms of the number of saliva samples taken per day, the number of days studied, and participants' demographic and health status. Significant individual differences of diurnal cycle in each of the four samples were found. In at least 10% of each sample no significant diurnal cycles was detected; however, the overall mean level of cortisol of those with flat cycles differed among the samples. These results suggest that some people do not have the expected diurnal rhythm of cortisol secretion. It is not clear what the determinants of this finding are or if there are any health consequences of having a flat cycle.

Adolescent↗
PubMed2001

Psychological, cardiovascular, and metabolic correlates of individual differences in cortisol stress recovery in young men.

The relationship of free salivary cortisol stress recovery and basal cortisol with psychological, cardiovascular and metabolic factors was investigated in 82 healthy young men. Blood pressure, heart rate, cortisol and mood were assessed during a single laboratory session involving mental arithmetic and speech tasks, and lipid profiles were analysed from a fasting blood sample. Participants were divided into high (n=31) and low (n=51) cortisol stress recovery groups on the basis of the magnitude of changes between the peak cortisol responses to tasks and the lowest levels recorded at the end of a 30 min post-stress rest period. The high recovery group showed consistent increases in cortisol following each of the tasks, while the low recovery group showed little change across the session. Cortisol levels in the two groups did not differ at the end of the post-stress recovery period. The groups were indistinguishable in age, body mass index, smoking and alcohol consumption, and did not differ in psychological characteristics including anxiety, depression and perceived social support. However, the high stress recovery group had elevated low density lipoprotein cholesterol and total cholesterol/high density lipoprotein ratios, suggesting raised cardiovascular disease risk. The high stress recovery group also reported greater psychological activation during tasks, and greater recent minor life stress, than did the low recovery group. There was no association between rate of cortisol recovery and cardiovascular responses to tasks. But resting cortisol was related to blood pressure stress reactivity, suggesting that cortisol played a permissive role in augmenting sympathetically-driven cardiovascular responses. The results suggest that the rate of cortisol stress recovery is associated with variations in metabolic risk, and with differences in psychological state but not trait characteristics.

Adult↗
PubMed2001

The relationship between stress induced cortisol levels and memory differs between men and women.

Epidemiological as well as experimental studies in elderly subjects have suggested that postmenopausal women are more susceptible to the memory impairing effects of elevated cortisol levels than elderly men. Little is known however about gender differences in the susceptibility to acute stress in young subjects. In the present study a total of 58 healthy young subjects learned a word list, with recall being tested after a brief distraction task. Twenty-two subjects had to learn the list after exposure to a psychosocial stressor (Trier Social Stress Test: TSST), while the remaining subjects served as controls. Free cortisol was determined via saliva samples taken before and 10 minutes after stress. Subjects exposed to the stressor, did not show impaired memory performance per se when compared to the control group. However the cortisol increase in response to the stressor was negatively correlated (r=-0.43, P<0.05) with the memory performance within the stressed group (i.e., subjects showing a larger cortisol response recalling less words than subjects showing only a small cortisol increase). Additional analysis revealed, that this correlation was solely caused by the strong association observed in men (r=-0.82, P<0.05), while no association was observed in women (r=-0.05, P=ns). Our data suggests, that gender modulates the association between cortisol and memory after stress. Whether these differences reflect activational effects of sex steroids or developmentally-programmed sex differences awaits to be determined.

Adult↗
PubMed2001

Effects of suckling on hypothalamic-pituitary-adrenal axis responses to psychosocial stress in postpartum lactating women.

In several studies lactation has been shown to be associated with a hypothalamic-pituitary-adrenal axis hyporesponsiveness to physical and psychological stressors. As it is not known whether the marked blunting of endocrine stress reactivity in women can be ascribed to suckling as a short-term effect or to lactation in general, the acute effects of suckling on the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary system responses to mental stress were investigated in lactating women. Forty-three lactating women were randomly assigned either to breast-feed or to hold their infants for a 15-min period with the onset 30 min before they were exposed to a brief psychosocial stressor (Trier Social Stress Test). Both breast-feeding and holding the infant yielded significant decreases in ACTH, total plasma cortisol, and salivary free cortisol (all P < 0.01). There were no significant differences in baseline hormone levels between the groups 1 min before the stress test. In response to stress exposure, ACTH, total plasma cortisol, salivary free cortisol, norepinephrine, and epinephrine were significantly increased in all lactating women (all P < 0.001). However, total cortisol and free cortisol responses to stress were attenuated in breast-feeding women (P = 0.001 and P = 0.067, respectively), who also showed significantly decreasing PRL levels during the stress test (P = 0.005). In addition, there was no change in plasma oxytocin or vasopressin in response to the stressor. Breast-feeding as well as holding led to decreased anxiety (P < 0.05), whereas, in contrast, stress exposure worsened mood, calmness, and anxiety in the total group (all P < 0.001). From these data we conclude that lactation in women, in contrast to that in rats, does not result in a general restraint of the hypothalamic-pituitary-adrenal axis response to a psychosocial stressor. Rather, suckling is suggested to exert a short-term suppression of the cortisol response to mental stress.

Adrenocorticotropic Hormone↗
PubMed2000

Testosterone and cognition in elderly men: a single testosterone injection blocks the practice effect in verbal fluency, but has no effect on spatial or verbal memory.

BACKGROUND: The relevance of the age-associated decline in testosterone for cognition in elderly men is still poorly understood. One hypothesis is that testosterone enhances spatial abilities, while it might impair verbal skills. METHODS: Thirty elderly men received a single testosterone (250 mg testosterone enanthate) or placebo injection. Cognitive performance was tested before and 5 days after treatment using spatial as well as verbal tests. RESULTS: Five days after injection, testosterone and estradiol levels were still in the supraphysiologic range. In the verbal fluency task, the placebo group, but not the testosterone group, showed a practice effect. Therefore, the testosterone group performed significantly worse than the placebo group after treatment. No effects of testosterone were observed in the other verbal and spatial tasks. CONCLUSIONS: The present finding, that testosterone blocks the practice effect in verbal fluency, partly supports the general idea that sex steroids modulate performance in tests with known gender differences. Moreover it demonstrates that these effects can occur rapidly. However, beneficial effects on spatial cognition or memory might need more time to develop and/or might only occur when a less pronounced testosterone increase is induced.

Aged↗
PubMed2000

A naturalistic evaluation of cortisol secretion in persons with fibromyalgia and rheumatoid arthritis.

OBJECTIVE: To compare cortisol levels, diurnal cycles of cortisol, and reactivity of cortisol to psychological stress in fibromyalgia (FM) and rheumatoid arthritis (RA) patients in their natural environment, and to examine the effect on results of accounting for differences among the groups in psychological stress and other lifestyle and psychosocial variables. METHODS: Participants were 21 FM patients, 18 RA patients, and 22 healthy controls. Participants engaged in normal daily activities were signaled with a preprogrammed wristwatch alarm to complete a diary (assessing psychosocial- and lifestyle-related variables) or provide a saliva sample (for cortisol assessment). Participants were signaled to provide 6 diary reports and 6 saliva samples on each of two days. Reports of sleep quality and sleep duration were also made upon awakening. RESULTS: FM and RA patients had higher average cortisol levels than controls; however, there were no differences between the groups in diurnal cycles of cortisol or reactivity to psychological stress. While the groups differed on stress measures, surprisingly, the patient groups reported less stress. Furthermore, statistically accounting for psychosocial- and lifestyle-related differences between the groups did not change the cortisol findings. CONCLUSION: The results provide additional evidence of hypothalamic-pituitary-adrenal axis disturbance in FM and RA patients. While such elevations are consistent with other studies of chronically stressed groups, the elevations in cortisol in this study did not appear to be due to ongoing daily stress, and there was no evidence of disturbed cortisol reactivity to acute stressors.

Adult↗
PubMed2000

Genetic factors, perceived chronic stress, and the free cortisol response to awakening.

Recent studies have demonstrated that the free cortisol response to awakening can serve as a useful index of hypothalamus-pituitary-adrenal axis (HPA) activity. This endocrine marker is rather consistent, shows good intraindividual stability across time and appears to be able to uncover subtle changes in HPA regulation. The present twin study investigated genetic factors as sources of the interindividual variation of the cortisol awakening response. Furthermore, the relationship between psychological variables and morning cortisol levels was studied. On two consecutive days saliva samples were collected 0, 30, 45 and 60 minutes after awakening in 52 monozygotic and 52 dizygotic twin pairs. Moreover, samples were obtained at 0800, 1100, 1500 and 2000 h. ('short day-time profile'). Additionally, the participants filled out questionnaires assessing chronic stress load, self-esteem and self-efficacy.Heritability estimates of h(2)=0.40 for the mean increase and of h(2)=0.48 for the area under the response curve indicate a significant impact of genetic factors on cortisol levels after awakening. However, no genetic influence on the short day-time profile could be observed. Furthermore, several aspects of perceived chronic stress, namely 'worries', 'social stress' and 'lack of social recognition' were significantly associated with the awakening cortisol response. The evidence for a medium-sized, yet distinct genetic influence on cortisol levels after awakening is discussed with regard to a potential clinical relevance of genetic determinants of HPA (re)activity. In line with several recent studies, the present findings further support the view that the cortisol awakening responses is consistently enhanced under chronic stress conditions.

Adolescent↗
PubMed2000

Effect of chronic psychosocial stress and long-term cortisol treatment on hippocampus-mediated memory and hippocampal volume: a pilot-study in tree shrews.

We investigated the impact of chronic psychosocial stress and long-term cortisol treatment on hippocampus-mediated memory processes and hippocampal volume in male tree shrews. By combining cognitive tests on a hole board, magnetic resonance imaging (MRI), and saliva cortisol analysis, we were able to follow in individual animals the stress- and cortisol-induced temporal effects on HPA axis activity and the hippocampus and its executive functions during 15 weeks. Four weeks of either cortisol treatment or psychosocial stress affected hippocampus-mediated memory. Cortisol-induced impairments were observed only at the end of the treatment phase while in stressed animals a negative effect on hippocampus-mediated memory was monitored after 7 weeks of recovery. A trend towards a reduction of the hippocampal volume was found in both experimental groups. The present preclinical study demonstrated that major life events, such as psychosocial stress, or chronic cortisol treatment leave traces in hippocampus-dependent memory. This finding requires systematic analysis to understand how brain areas critical for information processing such as the hippocampal formation are affected by stress and stress hormones.

Animals↗
PubMed2000

Tissue specificity of glucocorticoid sensitivity in healthy adults.

Contradicting data exist as to whether interindividual patterns in glucocorticoid (GC) sensitivity vary between different target tissues in humans. This study therefore measured GC sensitivity in 36 healthy subjects in three target tissues: the immune system; the cardiovascular system, and the hypothalamus-pituitary-adrenal axis. For this purpose, dexamethasone inhibition of lipopolysaccharide-induced interleukin-6 and tumor necrosis factor-alpha production in peripheral leukocytes, beclomethasone dipropionate-induced skin blanching, and suppression of cortisol levels after low-dose (0.5 mg) dexamethasone suppression test were determined in each subject. The results showed the expected glucocorticoid-induced suppression of interleukin-6 and tumor necrosis factor-alpha production (both P < 0.001), dose-dependent skin blanching (P < 0.001), and suppression of salivary cortisol response to awakening (P < 0.001). However, neither simple correlations nor cluster analysis revealed a significant association among the three bioassays for GC sensitivity. In contrast to the idea that interindividual variation in GC sensitivity is an intrinsic trait affecting all tissues, these results suggest that this variability is target tissue specific in healthy subjects.

Adult↗
PubMed2000

Psychosocial stress and HPA functioning: no evidence for a reduced resilience in healthy elderly men.

In order to investigate if HPA functioning is altered with age, the present study was conducted. Fifteen healthy elderly men (60-76 years; mean age 66.5 +/- 1.48 yrs.) and 12 younger adults (20-29 years; mean age 25.6 +/- 0.77 yrs.) collected salivary free cortisol profiles after awakening for basal HPA activity. Then, all subjects were exposed to the "Trier Social Stress Test" (TSST). This psychosocial stress protocol consists of a free speech and a mental arithmetic task of 13 minutes duration performed in front of an audience. Beside the assessment of endocrine and cardiovascular responses to the stressful task ratings of depression, mood and perceived stressfulness were obtained. Results show that younger and elderly men had similar morning cortisol profiles after awakening with both groups showing the expected rise after awakening (P=0.004). The TSST induced significant increases in ACTH, total plasma cortisol, saliva free cortisol, and heart rates (all P<0.0001). Regardless of age, both age groups showed comparable endocrine response patterns when confronted with the stressor. However, cardiovascular responses were significantly higher in younger men compared to elderly men (P=0.03). Catecholamine data revealed significant norepinephrine and epinephrine increases due to the stressor (both P<0.0001) with a trend toward elevated norepinephrine levels in elderly men (P=0.058). In sum, the investigated basal and response parameters of HPA functioning neither support the idea of a reduced resilience in healthy aged humans nor do they appear to strengthen assumptions derived from the so called "glucocorticoid cascade hypothesis".

Adaptation, Physiological↗