Acute cortisol administration increases sleep depth and growth hormone release in patients with major depression.

Acute administration of cortisol increases non-rapid-eye movement (non-REM) sleep, suppresses rapid-eye movement (REM) sleep and stimulates growth hormone (GH) release in healthy subjects. This study investigates whether cortisol has similar endocrine and electrophysiological effects in patients with depression who typically show a pathological overactivity of the hypothalamus-pituitary-adrenal (HPA) system. Fifteen depressed inpatients underwent the combined dexamethasone/corticotropin-releasing hormone test followed by three consecutive sleep EEG recordings in which the patients received placebo (saline) and hourly injections of cortisol (1mg/KG BW). Cortisol increased duration and intensity of non-REM sleep in particular in male patients and stimulated GH release. The activity of the HPA axis appeared to influence the cortisol-induced effects on non-REM sleep and GH levels. Stimulation of delta sleep was less pronounced in patients with dexamethasone nonsuppression. In contrast, REM sleep parameters were not affected by the treatment. These data demonstrate that the non-REM sleep-promoting effects of acute cortisol injections observed in healthy controls could be replicated in patients with depression. Our results suggest that non-REM and REM sleep abnormalities during the acute state of the disease are differentially linked to the activity of the HPA axis.

Changes of sleep architecture, spectral composition of sleep EEG, the nocturnal secretion of cortisol, ACTH, GH, prolactin, melatonin, ghrelin, and leptin, and the DEX-CRH test in depressed patients during treatment with mirtazapine.

The noradrenergic and specific serotoninergic antidepressant mirtazapine improves sleep, modulates hormone secretion including blunting of hypothalamic-pituitary-adrenocortical (HPA) activity, and may prompt increased appetite and weight gain. The simultaneous investigation of sleep electroencephalogram (EEG) and hormone secretion during antidepressive treatment helps to further elucidate these effects. We examined sleep EEG (for later conventional and quantitative analyses) and the nocturnal concentrations of cortisol, adrenocorticotropin (ACTH), growth hormone (GH), prolactin, melatonin and the key factors of energy balance, ghrelin, and leptin before and after 28 days of treatment of depressed patients (seven women, three men, mean age 39.9+/-4.2 years) with mirtazapine. In addition, a sleep EEG was recorded at day 2 and the dexamethasone-corticotropin-releasing hormone (DEX-CRH) test was performed to assess HPA activity at days -3 and 26. Psychometry and mirtazapine plasma concentrations were measured weekly. Already at day 2, sleep continuity was improved. This effect persisted at day 28, when slow-wave sleep, low-delta, theta and alpha activity, leptin and (0300-0700) melatonin increased, and cortisol and ghrelin decreased. ACTH and prolactin remained unchanged. The first two specimens of GH collected after the start of quantitative EEG analysis were reduced at day 28. The DEX-CRH test showed, at day 26, a blunting of the overshoot of ACTH and cortisol found at day -3. The Hamilton Depression score decreased from 32.1+/-7.3 to 15.5+/-6.7 between days -1 and 28. A weight gain of approximately 3 kg was observed. This unique profile of changes is compatible with the action of mirtazapine at 5-HT-2 receptors, at presynaptic adrenergic alpha 2 receptors, at the HPA system, and on ghrelin and leptin.

Ghrelin stimulates appetite, imagination of food, GH, ACTH, and cortisol, but does not affect leptin in normal controls.

Ghrelin, a growth hormone (GH) secretagogue receptor ligand was isolated from the stomach and hypothalamus of rats and humans. In rodents, ghrelin exerts distinct orexigenic action, probably as counterpart of the anorexigenic leptin. In humans, ghrelin infusion enhances appetite. It is unknown whether single intravenous (i.v.) injections of ghrelin affect human eating behavior. Therefore, we investigated the influence of a single i.v. bolus injection of 100 microg ghrelin on appetite, ideas about food, hormone levels, and glucose concentration in young control subjects. In order to test gender differences, we included five women and four men. After ghrelin administration, appetite was enhanced in eight of nine subjects. Seven probands reported a vivid, plastic image of their preferred meal. Furthermore, ghrelin stimulated an immediate increase in plasma levels of GH (area under the curve, mean+/-SEM 35+/-16 ng/ml x min after placebo [P] to 2808+/-533 ng/ml x min after ghrelin [G]; p<0.001), cortisol (5908+/-984 ng/ml x min [P] to 10179+/-1293 ng/ml x min [G]; p<0.001), and ACTH (922+/-103 pg/ml x min [P] to 3030+/-763 pg/ml x min [G]; p<0.02), whereas leptin levels remained unchanged. Contrary to placebo, glucose concentration did not decrease markedly after administration of ghrelin. Our data suggest that i.v. ghrelin stimulates appetite and images of food in young women and men. Obviously, leptin is not involved in these effects.

Hypothalamo-pituitary-adrenal function in patients with depressive disorders is correlated with baseline cytokine levels, but not with cytokine responses to hydrocortisone.

Dysfunction of the hyopthalamo-pituitary adrenal (HPA) system is frequently found in major depression. In addition, signs of non-specific inflammatory system activation have been reported. However, very little is known about interactions between the HPA and immune systems in depressive patients. To assess HPA system function, we performed a combined dexamethasone suppression and corticotropin-releasing hormone stimulation (DEX/CRH) test in 14 depressive patients. Moreover, baseline nocturnal plasma levels of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were measured. In addition, the system was challenged with an intraveneous pulsatile injection of hydrocortisone (1 mg/kg body weight in total) and again cytokine levels were measured across one night. Baseline TNF-alpha levels were negatively correlated with the amount of ACTH released upon CRH stimulation during the DEX/CRH test. Acute hydrocortisone administration suppressed TNF-alpha and IL-6 levels independently of baseline HPA system activity. We conclude that chronic HPA system overactivity in depressed patients might compromise the production of inflammatory cytokines under baseline conditions. However, the responsivity of the cytokine production to acutely administered glucocorticoids does not seem to correlate with the state of the HPA system.