Thomas Schürmeyer

Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome.

OBJECTIVE It has been suggested that a hypofunctional hypothalamic-pituitary-adrenal (HPA) axis in chronic fatigue syndrome could result in an exaggerated release of pro-inflammatory cytokines during stress. As pro-inflammatory cytokines are involved in the induction of sickness behavior and thus constitute a potential physiological correlate of stress-induced symptom exacerbation in chronic fatigue syndrome, we set out to evaluate the LPS-induced production of pro-inflammatory cytokines during psychosocial stress in CFS and healthy controls. METHOD Twenty-one CFS patients and 20 healthy controls matched for age and gender underwent a standardized psychosocial stress test (Trier social stress test, TSST). Adrenocorticotropine hormone (ACTH), salivary cortisol and plasma cortisol levels were measured before and repeatedly following exposure to the stressor. Lipopolysaccharide-stimulated production of interleukin-6 and tumor necrosis factor-alpha were assessed at baseline as well as 10 and 60 min after the stress test. RESULTS CFS patients showed an inverse stress-induced response pattern of LPS-stimulated cytokines responses in comparison to healthy controls, i.e. stimulated cytokine production decreased shortly after stress in CFS patients, while it increased in controls. Fatigue scores and basal LPS-induced cytokine levels were significantly associated for TNF-alpha in controls and for both cytokines in CFS patients. Stress-induced changes in stimulated cytokine production were not associated with general fatigue scores in the control group, whereas in the CFS group, fatigue scores were significantly correlated with integrated levels of LPS-induced cytokines. However, partial correlations revealed that these results were due to the high correlations with basal LPS-induced cytokine levels. CONCLUSION CFS patients do not show an exaggerated secretion of LPS-induced cytokines. Although cortisol responses to stress were normal, pro-inflammatory cytokine levels in CFS patients were significantly attenuated. Possible intracellular mechanisms, such as for example an enhanced sensitivity to inhibitory effects of glucocorticoids, a diminished responsivity to catecholaminergic stimulation, and a disruption of intracellular activation are discussed. Basal levels of stimulated pro-inflammatory Il-6 levels are generally related to fatigue scores. However, in CFS patients this association is of greater magnitude and can also be observed for TNF-alpha.

Changes in saliva testosterone after psychological stimulation in men

Saliva testosterone (ST) concentration was measured in 20 young adult and healthy men before, during and after the presentation of five different films. The films were selected to provoke erotic, sexual, aggressive, stressful and neutral stimulation, respectively. An increase in ST was found 15 min after the onset of both the erotic and the sexual stimulation, while a decline of ST levels was observed during the stressful movie showing dental surgery. No changes were found for either the neutral or the aggressive stimulant. Furthermore, no differences were found between ST levels before and after the showing of any of the films. Thus, saliva testosterone responds quickly to psychological stimulation, and may provide a practical alternative to testosterone measurements in serum under psychological test situations.

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.

Low-dose dexamethasone suppression test in chronic fatigue syndrome and health.

Objective Subtle dysregulations of the hypothalamus-pituitary-adrenal axis in chronic fatigue syndrome have been described. The aim of this study was to examine the negative feedback regulations of the hypothalamus-pituitary-adrenal axis in chronic fatigue syndrome. Methods In 21 patients with chronic fatigue syndrome and 21 healthy control subjects, awakening and circadian salivary free cortisol profiles were assessed over 2 consecutive days and compared with awakening and circadian salivary free cortisol profiles after administration of 0.5 mg of dexamethasone at 11:00 PM the previous day. Results Patients with chronic fatigue syndrome had normal salivary free cortisol profiles but showed enhanced and prolonged suppression of salivary free cortisol after the administration of 0.5 mg of dexamethasone in comparison to the control subjects. Conclusions Enhanced negative feedback of the hypothalamus-pituitary-adrenal axis could be a plausible explanation for the previously described alterations in hypothalamus-pituitary-adrenal axis functioning in chronic fatigue syndrome. Because similar changes have been described in stress-related disorders, a putative role of stress in the pathogenesis of the enhanced feedback is possible.

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”.

Stress-Induced Endocrine and Immunological Changes in Psoriasis Patients and Healthy Controls

Background: Clinical observations suggest that psychological stress can induce exacerbation of psoriasis. It is hypothesized that these stress effects on the course and outcome of psoriasis are caused by neuroendocrine modulation of immune functions. Therefore we investigated the cardiovascular, endocrine and immunological response to a laboratory stressor in psoriasis patients and healthy controls. Methods: Untreated (n = 7) and PUVA-treated (n = 4) psoriatics and healthy controls (n = 7) were exposed to a brief laboratory stressor (public speaking and mental arithmetic). Heart rate and blood pressure, catecholamine, cortisol, and DHEA plasma concentration, as well as distribution of T and NK lymphocytes were analyzed before, immediately after and 1 h after stress exposure. Results: Heart rate and blood pressure increased in all three groups during stress exposure with the most pronounced changes in PUVA-treated patients. Psoriasis patients displayed higher adrenaline values but diminished cortisol and DHEA plasma concentrations compared to controls. NK cell numbers (CD16+, CD56+), but not T lymphocyte subsets, increased immediately after stress exposure in untreated patients and controls. This effect was significantly diminished in PUVA-treated patients. Conclusions: The data of this pilot study indicate an enhanced stress-induced autonomic response and diminished pituitary-adrenal activity in psoriasis patients. PUVA treatment seems to interfere with the cardiovascular and NK cell response to acute psychological stress. Future studies will analyze the stress-induced neuroimmunological mechanisms in psoriatics in more detail.

Associations between neuroendocrine responses to the Insulin Tolerance Test and patient characteristics in chronic fatigue syndrome

OBJECTIVE Subtle dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis have been proposed as an underlying pathophysiological mechanism in chronic fatigue syndrome (CFS). This study attempted to assess the relationship between patient characteristics and HPA axis functioning using a neuroendocrine challenge test. METHOD A test battery designed to assess different dimensions of CFS was given to 18 CFS patients and 17 controls. To evaluate the integrity of the HPA axis, the Insulin Tolerance Test (ITT), a centrally acting neuroendocrine challenge test, was performed on patients and controls. ACTH, salivary free cortisol and total plasma cortisol levels were assessed as a measure of the HPA axis stress response. Correlations of patient characteristics were calculated with integrated responses for all endocrine parameters. RESULTS CFS patients had a significantly reduced area under the ACTH response curve (AUC) in the ITT. The AUC was significantly associated with the duration of CFS symptoms (r = -.592, P = .005) and the severity of fatigue symptomatology (r = -.41, P = .045). In addition, duration of CFS was correlated with the severity of fatigue symptoms (r = .38, P = .045). Similar associations were not observed for cortisol parameters. CONCLUSION It has been postulated that neuroendocrine dysregulations observed in CFS are of an acquired nature. The results of a strong association between the integrated ACTH response and the duration of CFS emphasizes the need to consider factors known to be risk factors for the chronicity of CFS symptoms, such as profound inactivity, deconditioning and sleep abnormalities, as possible candidates for secondary causes of neuroendocrine dysregulations in CFS.

Endocrine mechanisms of stress-induced DHEA-secretion

Acute psychological stress of a first time parachute jump stimulated DHEA and cortisol secretion in healthy volunteers. A significant shift from cortisol to DHEA occurred during this stress exposure. This effect was more pronounced in subjects receiving the β-adrenoceptor antagonist propranolol prior to the jump. In contrast, infusion of epinephrine (0.10 µ/kg/min) or norepinephrine (0.15 µg/kg/min) for 20 min neither affected DHEA plasma levels nor the DHEA/cortisol ratio. However, pretreatment with propranolol resulted in a significant increase of the DHEA/cortisol ratio upon infusion of the β-adrenoceptor agonist epinephrine. These data demonstrate that during acute psychological stress stimulation of adrenal steroid release is accompanied by a shift towards DHEA. Augmentation of this effect by β-adrenoceptor blockade indicates a β-adrenoceptor-dependent mechanism affecting DHEA release.

Enhanced glucocorticoid sensitivity in patients with chronic fatigue syndrome

Objective: Alterations of the immune–neuroendocrine interplay have been described in chronic fatigue syndrome (CFS). Employing a recently developed method, the study set out to investigate whether patients with CFS have an altered sensitivity to glucocorticoids (GCs) when under stress. Methods: A total of 21 CFS patients and 20 healthy age- and gender-matched controls underwent a standardized psychosocial stress test (Trier Social Stress Test, TSST). Salivary and plasma cortisol levels were measured repeatedly following exposure to the stressor. GC sensitivity was assessed in vitro by dexamethasone inhibition of lipopolysaccharide-stimulated production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNC-α). Results: Cortisol responses following the TSST did not differ significantly between CFS patients and healthy controls. GC sensitivity differed significantly between CFS patients and healthy controls, with CFS patients showing a greater sensitivity towards GCs (TNF-α: F1/39 = 7.32, P = 0.01; IL-6: F1/39 = 9.73, P = 0.004). Conclusion: Consistent with recent evidence, CFS patients are characterized by an enhanced sensitivity to glucocorticoids. The implications for secondary processes, such as the regulatory influence of glucocorticoids on immune processes, are discussed.

Effects of b-adrenoceptor-blockade on stress-induced adrenocorticotrophin release in humans

Abstract We investigated the mechanisms of stress-induced alterations in adrenocorticotrophin (ACTH) release. Tandem parachutists received either a placebo or the β-adrenoceptor antagonist propranolol prior to a first time parachute jump. Blood samples were drawn 4 h before, immediately after, and 1 h after the jump. Cortisol and catecholamine concentrations displayed a significant stress-induced increase in both groups. The ACTH plasma concentrations significantly increased in the placebo and the propranolol group, with significantly more pronounced changes in the propranolol-treated subjects compared to the placebo group. These data demonstrated a stress-induced increase of ACTH plasma concentrations in humans that was enhanced by β-blockade.