Biomedical subjects

A Steiger

Publications and source records attributed to A Steiger.

At least 37 records · Page 2Linked to original sources

PubMed2001

Effect of the GABAA agonist gaboxadol on nocturnal sleep and hormone secretion in healthy elderly subjects.

Aging is associated with a dramatic decrease in sleep intensity and continuity. The selective GABA(A) receptor agonist gaboxadol has been shown to increase non-REM sleep and the duration of the non-REM episodes in rats and sleep efficiency in young subjects and to enhance low-frequency activity in the electroencephalogram (EEG) within non-REM sleep in both rats and humans. In this double-blind, placebo-controlled study, we investigated the influence of an oral dose of 15 mg of gaboxadol on nocturnal sleep and hormone secretion (ACTH, cortisol, prolactin, growth hormone) in 10 healthy elderly subjects (6 women). Compared with placebo, gaboxadol did not affect endocrine activity but significantly reduced perceived sleep latency, elevated self-estimated total sleep time, and increased sleep efficiency by decreasing intermittent wakefulness and powerfully augmented low-frequency activity in the EEG within non-REM sleep. These findings indicate that gaboxadol is able to increase sleep consolidation and non-REM sleep intensity, without disrupting REM sleep, in elderly individuals and that these effects are not mediated by a modulation of hormone secretion.

Aged↗

PubMed2001

[NISAS-2000: The "Nationwide Insomnia Screening and Awareness Study". Prevalence and interventions in primary care].

AIM: To estimate the point prevalence of insomnia, recognition and prescription behavior in primary care. METHODS: Nationwide sample of 539 primary care settings along with their characterization (stage 1). Standardized assessment of all attenders (N = 19.155 patients) on the NISAS target day using a sleep questionnaire (PSQI) and additional questions to cover psychosocial and additional clinical variables. All patients were evaluated by the primary care doctors using a standardized clinical appraisal questionnaire, including a CGI-rating. RESULTS: Prevalence insomnia according to DSM-IV was 26.5%. Recognition of presence of any clinically significant sleep disorder was 72%, recognition of insomnia was poor 54.3%. 85.6% of insomnia patients were rated as chronic. Close to 50% of all insomnia cases did not receive a specific insomnia therapy. Herbals, followed by hypnotics and sedatives and antidepressants were the three most frequent treatments applied, psychotherapy was only seldomly indicated. DISCUSSION: NISAS provides for the first time nationally representative estimates of interventions for insomnia in primary care. The relatively low treatment rates and the high proportion of chronic patients receiving longterm prescription of benzodiazepines seem to be critical. Priorities for future agenda to improve this situation are discussed.

Adolescent↗

PubMed2000

Neuropeptide Y promotes sleep and inhibits ACTH and cortisol release in young men.

Anxiolytic and sedative effects of neuropeptide Y (NPY) are thought to involve inhibition of corticotropin-releasing hormone (CRH). Enhanced secretion of CRH plays a critical role in the pathophysiology of major depression, characterized by sleep disturbances, anxiety and loss of appetite. We examined for the first time in young men effects of intravenous injections of NPY (4x50 or 100 microg, n = 9 and 11, respectively, at 22.00, 23.00, 24. 00 and 01.00 compared to saline) on the sleep electroencephalogram (EEG; recorded from 23.00 to 07.00) and nocturnal secretion of adrenocorticotrophic hormone (ACTH), cortisol, growth hormone (GH), prolactin and leptin. Repeated measures MANOVA showed that ACTH secretion during the first half of the night was reduced by the lower dose of NPY only (F = 8.7, p<0.05), while cortisol secretion during the second half of the night was reduced regardless of the dose (F = 7.9, p<0.05). Regardless of the dose, NPY enhanced sleep period time and stage 2 sleep (F = 12.8 and 5.4, each p<0.05), and also reduced sleep latency and time awake (F = 4.9 and 4.4, each p<0.05) and modulated REM sleep. In summary, NPY promotes sleep and inhibits the hypothalamo-pituitary-adrenocortical (HPA) axis in humans, pointing to a possible role of NPY agonists for the development of novel treatment strategies for affective disorders.

Adrenocorticotropic Hormone↗

PubMed2000

Temporal EEG dynamics of non-REM sleep episodes in humans.

The process of the human non-rapid eye movement (non-REM) sleep period has not been clarified. Time-based analysis on sleep EEG may provide an explanation. We focused on chronological aspects of initiation and termination of non-REM episodes, using spectral analysis of sleep EEG. The subjects were healthy male volunteers (n14 Hz) and longer in lower frequency ranges (<14 Hz). There were significant differences in the rise and decay latencies between low and high sigma ranges, indicating that the whole frequency ranges were clearly separated at the middle of the sigma range (14 Hz). The rise and decay latencies were significantly different in lower frequency ranges. The clock time of the night significantly affected only the rise latencies of the delta (0.78-3.9 Hz), alpha (8.2-11.7 Hz) and low sigma (12.1-13.7 Hz) ranges. In conclusion, initiation and termination of non-REM sleep was represented by higher frequency ranges, whereas further evolution and devolution of non-REM sleep was represented by lower frequency ranges, and only the evolution process was affected by the clock time of the night.

Adult↗

PubMed2000

Modulation of the sleep electroencephalogram by estrogen replacement in postmenopausal women.

OBJECTIVE: We performed an examination of the effects of estrogen replacement on the sleep electroencephalogram in postmenopausal women. STUDY DESIGN: A sleep electroencephalogram was recorded in 11 postmenopausal women with and without estrogen administered by skin patch (50 microg of estradiol per day). RESULTS: Estrogen enhanced rapid-eye-movement sleep (50 +/- 4 vs 39 +/- 5 minutes, P <.05) and reduced time awake (12 +/- 5 vs 20 +/- 6 minutes, P <.05) during the first 2 sleep cycles. The normal decrease in slow-wave sleep and delta activity from the first to the second cycle (in percentage from the first cycle) was restored by estrogen (-56% +/- 9% vs -5% +/- 14% and -20% +/- 6% vs -2% +/- 5%; P <.05, respectively). Sigma electroencephalographic activity was increased by estrogen from the first to the second half of the night but decreased during baseline. CONCLUSION: Estrogen treatment after menopause can help to restore the normal sleep electroencephalogram pattern, which in turn might contribute to improved cognitive functioning.

Administration, Cutaneous↗

PubMed2000

Dehydroepiandrosterone--a neurosteroid.

Dehydroepiandrosteone (DHEA) and its sulfate ester (DHEAS) are the major secretory products of the human adrenal glands and serve as precursors for both androgenic and estrogenic steroids. DHEA/S concentrations are particularly high in the brain, and DHEA/S and related steroids can be synthesized de novo in brain glial cells. Therefore, the term 'neurosteroids' has been coined for these compounds. This review summarizes findings in neurosteroid physiology on a cellular and molecular level, and outlines current concepts of how these compounds modulate physiological functions of the brain. Today, despite promising preclinical and human data the present clinical studies provide only weak evidence, if any, in favour of a DHEA replacement therapy.

Animals↗

PubMed2000

Sexually dimorphic effects of GHRH on sleep-endocrine activity in patients with depression and normal controls - part I: the sleep eeg.

In patients with depression, enhanced secretion of ACTH and cortisol, a reduction in slow wave sleep (SWS) and a blunted nocturnal growth hormone (GH) surge have been described and attributed, at least partly, to an elevation of corticotropin-releasing hormone (CRH), hence a shift in the ratio between growth hormone-releasing hormone (GHRH) and CRH. We investigated the effects of pulsatile administration of GHRH (4x50 microgram, at hourly intervals between 2200 and 0100 h) on the sleep EEG (2300-0700 h) in patients with depression (16 females, 19 males, age range 19-76 years) and matched controls (20 females, 20 males). In patients compared with controls, NREM sleep and in particular stage 2 sleep was greatly decreased at baseline. GHRH treatment enhanced NREM sleep, and in particular stage 2 sleep in men, regardless of diagnosis, while decreasing it in women (F=6.0 and 7.1, p<0.05). In controls, aging was associated with a decrease in NREM sleep, including both SWS and stage 2 sleep (r= -0.45 r= -0.39, p<0.05), while in patients only SWS declined with age (r= -0.49, p<0.05). The significant decrease in NREM sleep including stage 2 sleep in patients with depression and elderly control subjects is compatible with the suggested role of sleep continuity and stage 2 sleep in cognitive functioning. GHRH promoted NREM sleep, stage 2 sleep and sleep continuity and might prove beneficial for improvement of cognitive function, at least in men. These data support the hypothesis that female gender, aging and depression are associated with a shift in the GHRH/CRH ratio towards CRH.

Adult↗

PubMed2000

Sexually dimorphic effects of GHRH on sleep-endocrine activity in patients with depression and normal controls - part II: hormone secretion.

In depression and aging an increase in nocturnal cortisol secretion and a blunted nocturnal growth hormone (GH) surge have been described. In normal young men, growth hormone-releasing hormone (GHRH) promotes GH release and reduces plasma cortisol. Here, we examined whether GHRH could help to restore sleep-endocrine regulation in patients with depression and aging. GHRH (4x50 microgram, at 2200, 2300, 2400 and 0100 h) or saline (placebo) was injected intravenously to 42 patients with depression (19 females, 23 males) and matched controls (age range 19-76 years). Blood samples were withdrawn at 20 min intervals between 2200-0700 h and analysed using Manova (D.F. 1, 72). Patients compared to controls had significantly higher levels of ACTH and cortisol, particularly during the first half of the night (F=9 and F=11.8, each p<0.05). GHRH reduced ACTH during the first and cortisol secretion during the second half of the night in males, regardless of diagnosis, but enhanced it in females (F=5.1 and F=4.0, each p<0.05). ACTH and cortisol secretion were inversely related to NREM and stage 2 sleep in patients (r= -0.42, -0.42 and r= -0.36, -0.39, respectively, each p<0.05) but not in controls. Our data suggest that: 1) female gender, depression and aging add-on to enhance HPA activity, and 2) hyperactivity of the HPA system and the decrease in NREM and in particular stage 2 sleep in depression are interrelated. In men, GHRH can restore some of the sleep-endocrine alterations associated with depression and aging.

Adrenocorticotropic Hormone↗

PubMed1999

Sleep and Its Modulation by Drugs That Affect GABA(A) Receptor Function.

Most sleeping pills are made up of chemical compounds that are ligands for allosteric modulatory binding sites on the GABA(A) receptor. Polysomnographic studies demonstrate that these hypnotics effectively increase the ability to fall and to stay asleep, but disrupt the physiological sleep profile (typical electroencephalograms (EEG) for the awake state and the different states of sleep are shown). Hence, there is an urgent need for sleep-promoting substances with a different mechanism of action. GABA analogues are one class of promising molecules.

Journal Article↗

PubMed1999

[Dependency of non-benzodiazepine hypnotics. Two case reports].

With the introduction of the non-benzodiazepine hypnotics zopiclone and zolpidem it was expected to have hypnotics without side effects and risks characteristically seen with benzodiazepines. We report two cases with high-dose usage and dependency of non-benzodiazepine hypnotics. Both patients were prescribed the drugs to treat sleep disturbances occurring during a depressive episode. While one patient had a polysubstance abuse there was no evidence for an abuse history in the other patient. To reduce withdrawal symptoms long-acting benzodiazepines were given to both patients. Thus, it seems that not only patients with a history of substance abuse but also patients with a psychiatric disorder are at risk for abuse of non-benzodiazepine hypnotics. Considering the increasing number of case reports with abuse and dependence of zopiclone and zolpidem it seems necessary to reevaluate the dependency risk of the currently available non-benzodiazepine hypnotics.

Adult↗

PubMed1999

Characterization of the sigma ligand panamesine, a potential antipsychotic, by immune response in patients with schizophrenia and by sleep-EEG changes in normal controls.

Panamesine (PAN) is a nearly specific sigma ligand. Recently, we showed that PAN in doses up to 90 mg/day improved psychometric variables in patients with an acute episode of schizophrenia. No side effects connected to the extrapyramidal motoric system occurred; there was even an absence of daytime sedation. We investigated the effects of PAN on plasma cytokine and soluble cytokine receptor levels and blood cell counts during 4 weeks in ten patients out of the previous study sample. Under PAN treatment, tumor necrosis factor (TNF)-alpha, soluble TNF receptors p55 and p75, and soluble interleukin-2 receptor levels were not increased and neither were monocyte and lymphocyte counts affected. This absence of immunomodulation is in contrast to clozapine, but similar to haloperidol treatment. In a second study, a single dose of PAN (30 mg) or placebo was administered at 2200 hours to ten young male controls in order to investigate changes in the sleep EEG under the substance. Sleep efficiency index increased, whereas time spent awake decreased. No significant changes in rapid eye movement (REM) sleep or non-REM parameters occurred. The sleep-EEG investigation showed sleep-consolidating effects of the drug, comparable to those of classical neuroleptics. Our results support the hypothesis that the sigma ligand PAN, which has antipsychotic properties, shares biological aspects with haloperidol.

Adjuvants, Immunologic↗

PubMed1999

Effects of growth hormone-releasing peptide-6 on the nocturnal secretion of GH, ACTH and cortisol and on the sleep EEG in man: role of routes of administration.

After repeated intravenous (i.v.) boluses of growth hormone-releasing peptide-6 (GHRP-6) we found recently increases of growth hormone (GH), corticotropin (ACTH) and cortisol levels and of the amount of stage 2 sleep. In clinical use, oral (p.o.), intranasal (i.n.) and sublingual (s.l.) routes of administration have advantages over i.v. administration. We compared the sleep-endocrine effects of 300 microg/kg of body weight (b.w.) GHRP-6 in enteric-coated capsules given p.o. at 21.00 h and of 30 microg/kg GHRP-6 i.n. or 30 microg/kg GHRP-6 sl. given at 22.45 h in normal young male controls with placebo conditions. After GHRP-6 p.o. secretion of GH, ACTH and cortisol remained unchanged. The only effect of GHRP-6 s.l. was a trend toward an increase in GH in the first half of the night. GHRP-6 i.n. prompted a significant increase in GH concentration during the total night and a trend toward an increase in ACTH secretion during the first half of the night, whereas cortisol secretion remained unchanged. Furthermore, after GHRP-6 i.n., sleep stage 2 increased in the second half of the night by trend, and spectral analysis of total night non-rapid eye movement (REM) sleep revealed a decrease of delta power by trend. In contrast sleep stage 2 decreased during the second half of the night after GHRP-6 p.o. Our data demonstrate that GHRP-6 is capable of modulating GH and ACTH secretion as well as sleep. However, the effects depend upon dosage, duration and route of administration.

Administration, Intranasal↗

PubMed1999

Modelling and exploring human sleep with event history analysis.

In this paper we propose the use of statistical models of event history analysis for investigating human sleep. These models provide appropriate tools for statistical evaluation when sleep data are recorded continuously over time or on a fine time grid, and are classified into sleep stages such as REM and nonREM as defined by Rechtschaffen and Kales (1968). In contrast to conventional statistical procedures, event history analysis makes full use of the information contained in sleep data, and can therefore provide new insights into non-stationary properties of sleep. Probabilities of or intensities for transitions between sleep stages are the basic quantities for characterising sleep processes. The statistical methods of event history analysis aim at modelling and estimating these intensities as functions of time, taking into account individual sleep history and assessing the influence of factors of interest, such as hormonal secretion. In this study we suggest the use of non-parametric approaches to reveal unknown functional forms of transition intensities and to explore time-varying and non-stationary effects. We then apply these techniques in a study of 30 healthy male volunteers to assess the mean population intensity and the effects of plasma cortisol concentration on the transition between selected sleep stages as well as the influence of elapsed time in a current REM period on the intensity for a transition to nonREM. The most interesting findings are that (a) the intensity of the nonREM-to-REM transitions after sleep onset in young men shows a periodicity which is similar to that of nonREM/REM cycles; (b) 30-45 min after sleep onset, young men reveal a great propensity to pass from light sleep (stages 1 or 2) into slow-wave sleep (SWS) (stages 3 or 4); (c) high cortisol levels imposed additional impulses on the transition intensity of (i) wake to sleep around 2 h after sleep onset, (ii) nonREM to REM around 6 h later, (iii) stage 1 or stage 2 sleep to SWS around 2, 4 and 6 h later and (iv) SWS to stage 1 or stage 2 sleep about 2 h later. Moreover, high cortisol concentrations at the beginning of REM periods favoured the change to nonREM sleep, whereas later their influence on a nonREM change became weak and weaker. As sleep data are also available as event-oriented data in many studies in sleep research, event history analysis applied additionally to conventional statistical procedures, such as regression analysis or analysis of variance, could help to acquire more information and knowledge about the mechanisms behind the sleep process.

Adult↗

PubMed1999

Hyporesponsiveness of the pituitary to CRH during slow wave sleep is not mimicked by systemic GHRH.

During slow wave sleep (SWS) pituitary responsiveness to CRH is reduced. Since GHRH is involved in the promotion of SWS in humans and rats, it was examined whether the blunted CRH-induced ACTH and cortisol release during SWS could be mimicked by systemic GHRH. Young healthy men (n = 7) participated in 4 sleep-endocrine protocols: (A) lights off at 23.00 h, intravenous injection of 50 microgram CRH during the first SWS period; (B) lights off at 01.00 h, injection of 100 microgram GHRH at 23.00 h, followed by 50 microgram CRH at 23.30 h; (C) lights off at 01.00 h, injection of 50 microgram CRH at 23.30 h, and (D) lights off at 23.00 h, saline treatment only (= baseline condition). The sleep EEG was recorded during the lights off period and blood samples, collected every 20 min between 22.00 and 07.00 h, were assayed for GH, cortisol and ACTH. There was no significant difference in the sleep-associated GH peak between protocols. Plasma ACTH was significantly higher following CRH administration during wakefulness compared with CRH administration during SWS (protocols B and C vs. A; area under the curve (AUC) 23. 00-03.00 h: 9.6 +/- 4.8 and 7.3 +/- 2.0 vs. 6.1 +/- 1.1 ng/ml x min; p < 0.05), while there was no significant difference in plasma ACTH concentration between the baseline condition and protocol A (CRH administration during SWS). Similarly, cortisol was significantly enhanced compared with baseline following CRH during wakefulness only. CRH induced an increase in EEG activity in the sigma frequency range, both when it was administered during wakefulness and SWS, while this effect was reduced by pre-treatment with GHRH. In summary, our data suggest that (1) the blunted CRH-induced release of ACTH and cortisol during SWS is not mimicked by systemic GHRH administration, and (2) CRH enhances sigma EEG activity possibly via modulation of afferent pathways from the median eminence to the thalamus and this effect is reduced by pre-treatment with GHRH.

Adrenocorticotropic Hormone↗

PubMed1999

On the gender differences in sleep-endocrine regulation in young normal humans.

Sleep-endocrine regulation in humans involves high activity of the somatotropic axis at the beginning of the night and an increase in the hypothalamic-pituitary-adrenocortical (HPA) system during the night. Gender differences were examined with regard to sleep-endocrine regulation in young healthy controls (10 men, 9 women). The sleep EEG was recorded (23:00-07:00 h) and plasma samples were collected and analyzed for GH, cortisol and ACTH at 20-min intervals. Cortisol secretion was significantly higher in females during the first half of the night (F = 9.9, p < 0.05), while ACTH was not different. In women, sleep-EEG analysis showed less slow wave sleep (SWS) during the second half of the night (F = 4.5, p < 0.05) and a significantly greater decrease in SWS and delta activity from the first to the second half of the night (F = 3.7 and 7.4, respectively, p < 0.05). Sigma activity increased during the night in women only (F = 3.7, p < 0.05). Our data are compatible with the hypothesis that in women compared to men activity of hypothalamic CRH neurons and central CRH release is greater, but is not reflected by greater HPA activity.

Adrenocorticotropic Hormone↗

PubMed1999

Nocturnal hormone secretion and the sleep EEG in patients several months after traumatic brain injury.

After severe traumatic brain injury (TBI), sleep disturbances and changes in hormone secretion are frequently observed. Similarly, in depression, abnormalities of sleep and neuroendocrine regulation are common. To test the hypothesis that the changes in brain-injured patients several months after injury are similar to those seen in patients with depression, the authors investigated simultaneously the sleep EEG and nocturnal hormone secretion in 13 young male nondepressed patients after TBI and 13 age-matched control subjects. The resulting data show a pattern of sleep-endocrine changes in patients after TBI, which has some similarities to that of patients with remitted depression.

Adult↗

PubMed1999

[Thyroid gland and sleep].

A set of data suggests that the thyroid gland plays a role in the bi-directional interaction between the electrophysiological and the endocrine components of sleep, e.g. the nonREM-REM-cycle and the patterns of nocturnal hormone secretion, respectively. In detail thyroid-stimulating hormone (TSH) and thyroxin (T4) show circadian rhythms. A specific relationship was observed between TSH and REM sleep. Blunted TSH levels were found in healthy elderly subjects and, probably due to overactivity of corticotropin-releasing hormone in patients with depression in comparison to young normal controls. Pulsatile administration of thyrotropin-releasing hormone induced a decrease of sleep efficiency and an earlier occurrence of the cortisol rise in normal controls. Slow wave sleep was reduced in patients with hypothyroidism in comparison to normal controls. The sleep EEG normalised after therapy.

Humans↗

PubMed1998

Mg2+ reduces ACTH secretion and enhances spindle power without changing delta power during sleep in men -- possible therapeutic implications.

Disturbances of Mg2+ metabolism have been reported in association with affective disorders, seizures in eclampsia, and alcohol withdrawal. Mg2+ has been reported to have N-methyl-D-aspartate (NMDA)-antagonistic and gamma-aminobutyric acid (GABA)-agonistic properties and modulation of GABA(A)- and NMDA-dependent systems is involved in pharmacological treatment of affective disorders and seizures. We studied the effect of Mg2+ on sleep electroencephalogram (EEG) and nocturnal hormonal secretion in men. Ten normal controls were given MgSO4 (3 g MgSO4 between 2030 hours and 2100 hours, followed by 0.5 g MgSO4 per hour until 0700 hours) or placebo i.v. according to a randomized schedule. The sleep EEG was recorded from 2300 hours to 0700 hours. Blood samples were taken from 2000 hours to 0700 hours for analysis of plasma corticotropin (ACTH), cortisol, growth hormone, prolactin and melatonin. The sleep-EEG power within the spindle frequency range (11.0-12.9 Hz) showed a significant increase in the third sleep cycle, but delta power was unchanged throughout the night. ACTH concentration was suppressed between 2200 hours and 0700 hours. No changes in cortisol, growth hormone prolactin or melatonin release were found. The findings are consistent with the assumption that Mg2+ has GABA(A)-agonistic or NMDA-antagonistic effects on sleep and nocturnal hormonal secretion and hence may be useful in controlling depressive symptoms and seizures.

Adrenocorticotropic Hormone↗