Biomedical subjects

Dirk H Hellhammer

Publications and source records attributed to Dirk H Hellhammer.

At least 19 recordsLinked to original sources

PubMed2007

The low-dose dexamethasone suppression test in fibromyalgia.

OBJECTIVE: Fibromyalgia syndrome (FMS) has been associated with decreased cortisol secretion. Patients with posttraumatic stress disorder (PTSD) exhibit similar hypocortisolism in the context of increased negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis. Because trauma and PTSD have been associated with fibromyalgia, we evaluated whether patients with fibromyalgia demonstrate increased HPA feedback sensitivity. METHOD: Baseline blood samples were obtained at 0800 h, and 0.5 mg of dexamethasone was administered to 15 female patients with FMS and 20 normal controls at 2300 h. Adrenocorticotropin (ACTH), cortisol, and dexamethasone levels were measured at 0800 h after dexamethasone intake. RESULTS: There were no group differences in mean ACTH or cortisol levels or in ACTH/cortisol ratio at baseline. After dexamethasone intake, patients with FMS exhibited more pronounced suppression of cortisol but not of ACTH, as well as increased ACTH/cortisol ratios compared with controls. Percent cortisol suppression was associated with pain and fatigue, while ACTH/cortisol ratio and dexamethasone availability were associated with stress and anxiety measures. CONCLUSION: Our results suggest increased sensitivity to glucocorticoid feedback, manifested at the adrenal level, in FMS.

Adrenocorticotropic Hormone↗

PubMed2006

Attenuation of the hypothalamic-pituitary-adrenal axis responsivity to the Trier Social Stress Test by the benzodiazepine alprazolam.

Little is known about effects of commonly used anxiolytic drugs on psychologically evoked responses of two major stress systems, the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal-medullary (SAM) axis. The purpose of the present study was to assess effects of the anxiolytic alprazolam on responses of the HPA and the SAM axes to a standardized psychosocial stress protocol, the Trier Social Stress Test (TSST). Forty-six healthy, non-smoking, non-medicated males, aged between 18 and 45 years, were invited once to the laboratory and received a single oral dose of 1mg alprazolam or placebo, respectively, 1h prior to the TSST. The secretion of ACTH, cortisol, epinephrine, norepinephrine as well as changes in heart rate, blood pressure, and psychological states (anxiety, wakefulness, good mood, calmness) in response to the TSST were measured. Subjects pre-treated with alprazolam showed a strongly blunted response of ACTH as well as total and free cortisol to the TSST. Whereas alprazolam-treated subjects displayed significantly lower systolic blood pressure immediately before the TSST, neither the secretion of epinephrine, norepinephrine nor changes of heart rate in response to the stress test differed from placebo-treated subjects. Regarding psychological parameters, alprazolam clearly decreased subjective ratings on the questionnaire scale "wakefulness" and increased ratings on the scale "good mood", whereas ratings on scales assessing "state anxiety" or "agitation" were not affected. In healthy subjects, we observed a dissociation of the effects of alprazolam on the endocrine and the autonomic response to psychosocial stress. The psychological responses seemed to be masked by sedative properties of alprazolam.

Adolescent↗

PubMed2006

A common polymorphism in the mineralocorticoid receptor modulates stress responsiveness.

CONTEXT: Mineralocorticoid receptors (MR) mediate the action of aldosterone on sodium resorption in kidney tubular cells, but in brain they respond to the glucocorticoid cortisol in stress regulation and cognitive processes. OBJECTIVE: The objective of the study was to investigate the role of the MR gene variant I180V in the neuroendocrine response to a psychosocial stressor and in electrolyte regulation. DESIGN: Associations between the MRI180V and outcome variables in a healthy cohort subjected to psychosocial challenge (Trier Social Stress Test) and in a mild hypertensive cohort exposed to acute salt loading (Weinberger's test) were investigated. In vitro transactivational assays were applied to compare the effects of cortisol and aldosterone on the MRI180V. RESULTS: Carriers of the MR180V allele showed higher saliva (P < 0.01), plasma cortisol (P < 0.01), and heart rate responses (P < 0.05) to the Trier Social Stress Test than noncarriers (MR180I). After 3 d of a normal salt diet and the Weinberger's test, no association was found with urinary sodium excretion, plasma aldosterone, and plasma renin activity or with changes in blood pressure, aldosterone, and renin responses. In vitro testing of the MR180V allele revealed a mild loss of function using cortisol as a ligand, compared with the MR180I allele. Significantly higher doses of cortisol were needed for half-maximal induction on the TAT-1 (P < 0.002), TAT-3 (P < 0.03), or mouse mammary tumor virus (P < 0.02) promoters, whereas maximal induction was not different. These differences were not observed using aldosterone as a ligand. CONCLUSION: The findings reveal that cortisol and heart rate responses to a psychosocial stressor are enhanced in carriers of the MR180V variant.

Adaptation, Biological↗

PubMed2006

The heritability of perceived stress.

BACKGROUND: Exploration of the degree to which perceived chronic stress is heritable is important as these self-reports have been linked to stress-related health outcomes. The aims of this study were to estimate whether perceived stress is a heritable condition and to assess whether heritability estimates vary between subjective stress reactivity and stress related to external demands. METHOD: A sample of 103 monozygotic and 77 dizygotic twin pairs completed three questionnaires designed to measure perceived stress: the Perceived Stress Scale (PSS), the Measure for the Assessment of Stress Susceptibility (MESA) and the Trier Inventory for the Assessment of Chronic Stress (TICS). The TICS assesses the frequency of stressful experiences on six scales, the MESA assesses subjective stress reactivity, and the PSS takes both factors into account. RESULTS: A multivariate model-fitting procedure revealed that a model with common additive genetic and shared environmental factors best fit the eight scales (PSS, MESA, six TICS scales). Heritabilities for the best-fitting model varied between 5% and 45%, depending on the scale. CONCLUSIONS: The present data suggest that perceived stress is in part heritable, that nearly half of the covariance between stress scales is due to genetic factors, and that heritability estimates vary considerably, depending on the questionnaire. Beyond methodological considerations that pertain to the validity of the questionnaires, these data suggest that studies assessing the heritability of perceived chronic stress should take the specific questionnaire focus into account.

Adult↗

PubMed2006

Parity does not alter baseline or stimulated activity of the hypothalamus-pituitary-adrenal axis in women.

Pregnancy is associated with considerable physiological adaptations, some of which long outlast the state of pregnancy. Although it is well documented that pregnancy produces alterations of the hypothalamus-pituitary-adrenal axis, the longer-term effects of pregnancy on this system have not been systematically examined in humans. Subjects in the present study were 159 nulliparous and 265 parous women. Data analysis revealed no impact of parity on baseline activity (salivary cortisol: response to awakening, F </= .03, day profile: F </= 3.89, both n.s.). In a subsample, similar results were obtained for dexamethasone-suppressed salivary cortisol levels (all F </= 1.45 n.s., n = 45), as well as salivary cortisol, total cortisol, and ACTH responses to stimulation with a psychosocial stress protocol (all F </= .93 n.s., n = 47). These findings suggest that parity is not associated with long-term alterations of hypothalamus-pituitary-adrenal axis activity, and postpregnancy measures can, therefore, be used as proxy markers for a woman's prepregnancy status of this system.

Adrenocorticotropic Hormone↗

PubMed2005

Trait anxiety moderates the impact of performance pressure on salivary cortisol in everyday life.

Stress and negative affective states are associated with cortisol in everyday life. However, it remains unclear what types of stressors and which affective states yield these associations, and the effect of trait anxiety is unknown. This study investigates the associations of specific task-related stressors and negative affective states in everyday life with salivary cortisol, and explores the mediating and moderating role of state negative affect and trait anxiety, respectively. Salivary cortisol, subjective stress, and state negative affect were measured three times a day on 2 days in 71 participants in everyday life, using a handheld computer to collect self-reports and time stamps and an electronic device to monitor saliva sampling compliance. Stress measures comprised the experience of performance pressure and failure during daily tasks; measures of negative affect comprised worn-out, tense, unhappy, and angry. Effects were tested using multilevel fixed-occasion models. Momentary performance under pressure was related to higher momentary cortisol measures, while mean task failure was related to lower daily cortisol concentrations. The association of performance pressure with cortisol varied between subjects, and this variation was explained by trait anxiety, yielding stronger associations in participants scoring high on trait anxiety. No evidence was found for a mediating role of state negative affect. These results describe the well-documented associations of everyday stressors and affect with salivary cortisol more precisely, suggesting that performance pressure is a significant condition related to short-term changes in cortisol. Subjects scoring high on trait anxiety seem to process stress-relevant information in a way that amplifies the association of performance pressure with reactions of the hypothalamus-pituitary-adrenal axis.

Activities of Daily Living↗

PubMed2005

Morningness and eveningness: the free cortisol rise after awakening in "early birds" and "night owls".

We investigated salivary cortisol profiles in the first hour after awakening in morning versus evening chronotypes. Chronotypes were defined by Horne and Ostberg's Owl-and-Lark-Questionnaire. In a sample of 112 healthy, day-active young men, we identified 9 morning and 29 evening chronotypes. Saliva samples were collected 0, 30, 45, and 60min after awakening on 2 consecutive days. Log-transformed cortisol levels were analyzed with General Linear Model procedures (GLMs) and awakening time and sleep duration were entered as covariates. On both days, a significant main effect of chronotype emerged (both p=0.02), and this effect could not be explained by differences in awakening time or sleep duration. The present data support the idea that morning relative to evening chronotypes might show higher cortisol levels in the first hour after awakening. In sum, individual chronotype should be acknowledged as one further possible source of interindividual variability in the cortisol rise after awakening.

Adult↗

PubMed2005

Habituation of cortisol responses to repeated psychosocial stress-further characterization and impact of genetic factors.

Although a rapid response habituation to repeated stress exposure is a key characteristic of the hypothalamus-pituitary-adrenal (HPA) axis, several studies document a substantial inter-individual variability of such HPA response patterns. In order to further investigate the individual differences in the habituation of this important neuroendocrine system to psychosocial stress, 54 male twin pairs were exposed to moderate psychosocial stress on three occasions, each exposure separated by a 1-week interval. Additionally, an ACTH(1-24) stimulation test (1 microg) and a dexamethasone suppression test (0.5mg) were performed. Although on average the expected decrease of mean cortisol and ACTH responses across stress exposures was observed, only 52% of the subjects showed this well-documented general decline and almost 16% of the participants even showed a response sensitization across sessions. Furthermore, a weak habituation was related to low cortisol responses to both the first stress exposure as well as the ACTH challenge. Moreover, genetic analyses did not reveal any evidence for a substantial heritability of the individual cortisol response habituation or an association between this habituation and two common polymorphisms in the glucocorticoid receptor gene.

Adaptation, Physiological↗

PubMed2005

Birth weight is associated with salivary cortisol responses to psychosocial stress in adult life.

Fetal programming of the hypothalamus-pituitary-adrenal (HPA) axis was proposed as one mechanism underlying the link between prenatal stress, adverse birth outcomes (particularly low birth weight) and an enhanced vulnerability for several diseases later in life. In recent studies, birth weight was significantly related to basal cortisol levels as well as to cortisol responses to pharmacological stimulation. In order to investigate the association between cortisol responses to psychological challenge, birth weight and length of gestation, 106 young healthy males were exposed to the 'Trier Social Stress Test'. Salivary cortisol responses to the stress exposure were significantly and inversely related to the subjects' birth weight, while the analysis of the impact of gestational age yielded inconsistent results. This finding is consistent with the concept of fetal programming of the HPA axis and provides the first preliminary evidence for an association between birth weight and adrenocortical responses to psychosocial stress. As the investigated subjects were twins, possible implications of this sample characteristic for the present findings are discussed.

Adaptation, Physiological↗

PubMed2005

A new view on hypocortisolism.

Low cortisol levels have been observed in patients with different stress-related disorders such as chronic fatigue syndrome, fibromyalgia, and post-traumatic stress disorder. Data suggest that these disorders are characterized by a symptom triad of enhanced stress sensitivity, pain, and fatigue. This overview will present data on the development, mechanisms and consequences of hypocortisolism on different bodily systems. We propose that the phenomenon of hypocortisolism may occur after a prolonged period of hyperactivity of the hypothalamic-pituitary-adrenal axis due to chronic stress as illustrated in an animal model. Further evidence suggests that despite symptoms such as pain, fatigue and high stress sensitivity, hypocortisolism may also have beneficial effects on the organism. This assumption will be underlined by some studies suggesting protective effects of hypocortisolism for the individual.

Humans↗

PubMed2005

Predicting posttraumatic stress symptoms from pretraumatic risk factors: a 2-year prospective follow-up study in firefighters.

OBJECTIVE: Most studies focusing on risk factors for posttraumatic stress disorder (PTSD) have used retrospective study designs. Only a small number of studies have prospectively examined risk factors in the immediate aftermath of trauma exposure in predicting PTSD symptoms. The purpose of this study was to identify predictive risk factors for posttraumatic stress symptoms and comorbid psychopathological symptoms present during the time before exposure to traumatic stress in a high-risk population. METHOD: Forty-three professional firefighters were assessed immediately after basic training (baseline) and at 6, 9, 12, and 24 months after entry into firefighter service. Subjects were screened for psychopathological symptoms, including symptoms of PTSD, depression, and anxiety. Subjects were also characterized with regard to personality traits such as self-efficacy, hostility, and alexithymia. Neuroendocrine activity was assessed by examination of awakening and diurnal salivary cortisol profiles and 24-hour urinary catecholamine excretion. Multiple linear regression analysis was used to analyze posttraumatic stress symptoms at 24-month follow-up as a function of pretraumatic characteristics. RESULTS: A high level of hostility and a low level of self-efficacy at baseline accounted for 42% of the variance in posttraumatic stress symptoms after 2 years. Subjects who had both risk factors at baseline showed a significant increase in measures of PTSD symptoms, depression, anxiety, general psychological morbidity, global symptom severity, and alexithymia during the 2-year period. Biological characteristics were not predictive of the development of psychopathological symptoms. CONCLUSIONS: These results suggest that specific personality traits may constitute markers of vulnerability to the development of psychopathological symptoms after trauma exposure. Early identification of preexisting risk factors is needed to provide effective prevention and intervention for individuals who are at risk of developing trauma-related disorders.

Adult↗

PubMed2004

Selective amnesic effects of oxytocin on human memory.

The neuropeptide oxytocin is essential for mammalian parturition and lactation. Recent animal studies suggest that oxytocin is also implicated in the central nervous control of behavior including learning and memory. There has been little investigation, however, of the impact of oxytocin on human memory. The purpose of this study was to investigate the effect of a single dose of intranasal oxytocin on implicit and explicit memory in humans. In a placebo-controlled, double-blind study, 38 healthy men were randomly assigned to receive intranasal oxytocin (24 IU) or placebo 50 min before the study phase (incidental learning). Memory was measured using three different memory tests: an implicit perceptual test (word stem completion), an implicit conceptual test (category-cued semantic association), and an explicit test (cued recall). Due to the reproductive-biological role of oxytocin and the impact of adequate environmental conditions for the stimulation of behavioral effects of oxytocin known from animal research, we used semantic word stimuli with reproduction-related vs. neutral meaning. Oxytocin significantly impaired recall performance as compared with placebo treatment irrespective of the meaning of words in the cued recall test. In the implicit conceptual test, characterized by a deepened information processing, compared with placebo, oxytocin significantly impaired only the overall generation of associated target words with reproduction relevant meaning, whereas no significant difference between oxytocin and placebo was obtained for neutral words. These findings concur with data from animal research suggesting that central oxytocin selectively influences memory performance depending on the kind of memory test used and, more importantly, the psychobiological relevance of stimuli.

Administration, Intranasal↗

PubMed2004

Acute HPA axis responses, heart rate, and mood changes to psychosocial stress (TSST) in humans at different times of day.

There is evidence showing that HPA axis responses to pharmacological provocation depend on time of day with larger cortisol responses in the afternoon and evening compared to the morning hours. However, it is still unknown whether HPA axis responses to psychological stress are affected by time of day and whether they can be assessed with equal reliability in the morning and afternoon, respectively. The present reanalysis is based on five independent studies conducted in the same laboratory by and. All subjects were confronted with the Trier Social Stress Test (TSST) either in the morning or in the afternoon. The total sample consisted of 180 adults with 115 younger (49 females, 66 males) and 65 older adults (32 females, 33 males). All ANCOVA results controlled for possible age and gender effects. Stress-related free salivary cortisol, total plasma cortisol and ACTH net increases did not differ according to time of day (all p = n.s.). However, as expected pre-stress free salivary and total plasma cortisol levels differed significantly between the morning and afternoon group (both p < 0.005), leading to a significantly higher free cortisol area under the curve (AUC) in the morning (p = 0.02). Taken together, these observations suggest that the adrenal glands may be more sensitive to ACTH in the morning. Additionally, higher basal salivary cortisol levels were related to a lower stress-related net increase in salivary cortisol (p = 0.02), total plasma cortisol (p < 0.0001), and marginally ACTH (p = 0.09). Stress-related heart rate increases did not differ between groups (p = n.s.). The finding that the TSST-induced mood change was differentially affected by time of day requires further exploration. We conclude that comparable HPA axis and heart rate stress responses to psychosocial stress can be measured in the morning and afternoon.

Adrenocorticotropic Hormone↗

PubMed2004

Free cortisol awakening responses are influenced by awakening time.

Psychobiological investigations on the hypothalamus-pituitary-adrenal (HPA) axis depend on markers that adequately describe the activity of this system. There is evidence that the free cortisol response to awakening, proposed as a marker for the HPA axis, can be influenced by time of awakening. To further investigate this possible confounder, 24 shift working nurses and 31 female students on a regular sleep-wake cycle collected saliva samples 0, 30, 45 and 60 minutes after awakening. Nurses were investigated on the first and second day of their early (awakening: 04:00-05:30 h), late (awakening: 06:00-09:00 h), and night shift (awakening: 11:00-14:00 h), respectively. Students were studied after taking a short nap on two consecutive weekdays (awakening: 18:45-20:30 h). Mean cortisol levels after awakening increased significantly under all three shift conditions (p<0.01), but decreased in the student sample (p<.05). Within the three shift conditions, cortisol responses following waking in the early shift were more pronounced than in late (p<.01) and night shift (p<.05). The present study shows that in a sample with a large range of awakening times, an impact of this variable on the cortisol awakening response can be observed. The data furthermore strongly suggest that waking up per se is insufficient for adrenocortical stimulation.

Adrenal Cortex Function Tests↗

PubMed2004

A psychobiological perspective on genetic determinants of hypothalamus-pituitary-adrenal axis activity.

From the perspective of psychobiological stress research we present a brief overview of findings documenting a significant impact of genetic factors on the activity of the hypothalamus-pituitary-adrenal (HPA) axis. Quantitative genetic studies in twins as well as association studies, primarily on polymorphisms in the glucocorticoid receptor gene, are depicted. Recent findings suggest that the collaboration of psychobiology and molecular genetics is a promising interdisciplinary approach that will significantly contribute to the understanding of the mechanisms underlying the link between stress, the HPA axis, and HPA-related clinical states.

Animals↗

PubMed2004

Influence of stress during pregnancy on HPA activity and neonatal behavior.

Prenatal maternal stress has been shown to impair birth outcome and behavioral functioning in nonhuman primate offspring. Little is known about the effects of prenatal stress on behavioral development in humans. We assessed the effect of self-reported prenatal stress on behavioral characteristics of 81 newborns using the Neonatal Behavioral Assessment Scale (NBAS). We suspected that high levels of perceived chronic stress during pregnancy may negatively affect the brain development of the fetus, reflected in poorer behavioral maturity and higher irritability. We found a poorer performance of newborns from high stressed mothers in the NBAS.

Adolescent↗

PubMed2004

Preliminary evidence of altered sensitivity to benzodiazepines as a function of maternal care in the rat.

Variations in maternal care over the first week of life alter the expression of genes encoding for various subunits of the GABA(A)/benzodiazepine (BZ) receptor in the amygdala, a brain region associated with fear behavior. Increased maternal licking/grooming and arched-back nursing are associated with decreased fearfulness and enhanced expression of the subunits that confer BZ sensitivity. In these studies we found that the offspring of high licking/grooming-arched-back nursing mothers also showed increased behavioral sensitivity to acute BZ treatment, suggesting a functional relation between the effect on gene expression and fear behavior.

Animals↗

PubMed2004

Differential heart rate reactivity and recovery after psychosocial stress (TSST) in healthy children, younger adults, and elderly adults: the impact of age and gender.

In addition to numerous reports about psychophysiological stress responses to acute stressors, there are few data available on gender differences of stress-induced heart rate responses in multiple age groups applying the same psychological stressor. Second, the assessment of poststress recovery appears to be neglected in the empirical literature. For this study, data from 5 independent studies were reanalyzed to investigate the impact of age and gender on heart rate responses and poststress recovery to a standardized psychosocial stress task (Trier Social Stress Test; TSST) in 28 children, 34 younger adults, and 26 older adults. As expected, prestressor baselines correlated significantly with chronological age (r = -.27, p =.01). There was a marked age-related decrease in the heart rate stress response (p =.0003) with children and younger adults showing significantly higher increases than elderly persons. The analysis of gender effects showed that girls had higher heart rate increases during the stress exposure than boys (p =.03). In younger adults, stress responsivity was also higher in women (p =.03). Peak heart rate responses were comparable in older men and women, with only men returning to prestressor baselines during the observation period. In sum, this reanalysis revealed differential heart rate responses and recovery after exposition to the TSST in healthy children, younger adults, and elderly adults.

Adaptation, Psychological↗