Nocturnal melatonin and cortisol secretion in newly admitted psychiatric inpatients

Summary Melatonin secretion has been suggested as a marker of both circadian and noradrenergic dysfunction in affective disorders. Seventy-two newly admitted psychiatric inpatients [49 with major depressive disorder (MDD), 12 with schizophrenia, and 11 with intermittent depressive disorder (IDD)] underwent neuroendocrine screening at 0200, 0800, 1600 and 2300 hours prior to and the day following dexamethasone administration. All groups showed a drop in cortisol following dexamethasone. Dexamethasone nonsuppression was found in 20 of 49 patients with MDD, in none of the schizophrenics and in none of those with intermittent depressive disorder. Mean melatonin levels decreased significantly after the administration of dexamethasone across all four groups. Overall, the schizophrenic group had a significantly greater mean melatonin level than each of other three groups, whereas the three depressive groups did not differ significantly from one another. Only at 2300 hours did both the schizophrenic group and the MDD patients with normal dexamethasone suppression show significantly greater melatonin levels than the MDD patients with dexamethasone nonsuppression or the IDD group. The observed trend for a low circadian melatonin profile in IDD patients with superimposed personality disorders is puzzling.     

Nocturnal prolactin and cortisol secretion and recovery from melancholia

Spontaneous prolactin and cortisol patterns were determined at 20 min intervals over 3 hr during the night in eight patients with melancholia, both during illness and after treatment with amitriptyline. Mean plasma prolactin levels were greater after recovery in the seven patients who responded to treatment. Mean cortisol secretion decreased upon recovery from melancholia, and such changes in two patients paralleled normalization of dexamethasone suppression test responses. The influence of assumptions of lack of interaction on the statistical significance of the analysis of variance with repeated measures for prolactin and cortisol values was evaluated.     

Bulimia, bulimia-anorexia and nocturnal secretion of melatonin and cortisol

The authors compared nocturnal variations of melatonin (MT) and cortisol levels in subjects with bulimia (n = 12), 6 with a normal body weight and 6 with anorexia nervosa, as well as 6 control subjects. The hypothesis, formulated for anorexia nervosa, that a decrease of noradrenergic activity induces a decrease of pineal activity, therefore a decrease of melatonin secretion, was not confirmed by our study. Moreover, in subjects with bulimia in the absence of anorexia nervosa, no significant decrease of nocturnal melatonin secretion was reported. Significant differences were due to cortisol variations when comparing MTmax/Cmin ratios. Melatonin did not add any complementary biological cue for diagnostic assessment for subjects with eating disorder and depression. The results of this study suggest that melatonin does not appear to be a useful biological marker in bulimia.     

Nocturnal ghrelin, ACTH, GH and cortisol secretion after sleep deprivation in humans

Ghrelin is an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor. It is hypothesised to play a key role in energy balance stimulating food intake and body weight. Besides GH-releasing hormone (GHRH) and somatostatin, it is thought to be a regulating factor of GH release. Ghrelin also appears to be involved in sleep regulation. We showed recently that ghrelin promotes slow-wave sleep and the nocturnal release of GH, cortisol and prolactin in humans. Similarly, promotion of non-rapid-eye-movement (NREM) sleep was reported in mice after systemic ghrelin. If ghrelin is a factor that induces and/or maintains sleep, it should be enhanced after a period of sleep deprivation (SD). To clarify this issue, nocturnal ghrelin, GH, ACTH and cortisol plasma concentrations were determined and simultaneously sleep electroencephalogram (EEG) was recorded (2300-0700 h) during sleep before and after 1 night of total SD in 8 healthy subjects. Compared to baseline, ghrelin levels increased earlier by a non-significant trend, already before the beginning of recovery sleep. Further a non-significant trend occurred, suggesting higher ghrelin secretion in the first half of the night. The ghrelin maximum was found significantly earlier after SD than at baseline. GH secretion during the first half of the night and total night after SD were elevated. ACTH and cortisol were also elevated, which was most pronounced during the second half of the night. No effects of SD on the time of the maximum were found for GH, ACTH and cortisol. The increase in ACTH after SD is a novel finding. Whereas the effects of SD on ghrelin levels were relatively weak, our findings are in line with the hypothesis that ghrelin is a sleep-promoting factor in humans. Ghrelin may be involved in sleep promotion after SD.     

Acupuncture increases nocturnal melatonin secretion and reduces insomnia and anxiety: a preliminary report

The response to acupuncture of 18 anxious adult subjects who complained of insomnia was assessed in an open prepost clinical trial study. Five weeks of acupuncture treatment was associated with a significant (p = 0.002) nocturnal increase in endogenous melatonin secretion (as measured in urine) and significant improvements in polysomnographic measures of sleep onset latency (p = 0.003), arousal index (p = 0.001), total sleep time (p = 0.001), and sleep efficiency (p = 0.002). Significant reductions in state (p = 0.049) and trait (p = 0.004) anxiety scores were also found. These objective findings are consistent with clinical reports of acupuncture's relaxant effects. Acupuncture treatment may be of value for some categories of anxious patients with insomnia.     

Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder.

Plasma levels of melatonin and cortisol were measured over a 24-hour period in seven patients with primary obsessive-compulsive disorder (OCD) and seven matched healthy control subjects. In OCD patients, the 24-hour secretion of melatonin was reduced as compared with that in healthy control subjects, whereas its circadian rhythm was preserved. In addition, in OCD patients, the overall secretion of cortisol was higher than that in control subjects, but there was no change in the circadian pattern of cortisol secretion. No correlation was found between clinical parameters and hormone levels.     

Nocturnal plasma prolactin and cortisol levels in epileptics with complex partial seizures and primary generalized seizures

The nocturnal pattern of plasma prolactin (PRL) and cortisol in male epileptics with complex partial seizures and primary generalized seizures was studied by all-night polygraphic recordings with continuous video monitoring and sequential blood sampling at 30-minute intervals. Mean nocturnal plasma PRL concentrations in both groups of epileptics were significantly elevated when compared with nonepileptic control subjects studied in a similar fashion. Eight subclinical and three clinical partial seizures were recorded during sleep. Although a tenfold increase of plasma PRL level occurred following a short brief clinical complex partial seizure, there was no direct correlation between single subclinical partial seizures and nocturnal fluctuations of plasma PRL concentrations. We did not observe recognizable plasma cortisol changes following partial seizures during sleep, nor significant differences of mean nocturnal plasma cortisol levels between epileptics and controls. The data obtained in this environmentally controlled study indicate that postictal elevation of plasma PRL is a specific phenomenon related to seizure discharges; however, failure of such a rise does not exclude partial seizures.     

A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression

The temporal organization of plasma melatonin and cortisol secretion was examined in healthy rested controls and in depressed patients: 11 patients suffering from a primary affective disorder (10 female, 1 male) and 8 male controls were studied over a 24-hr period; blood was collected at 2-hr intervals during the day at 1-hr intervals at night. Plasma melatonin and cortisol levels were determined by radioimmunoassay. In addition, melatonin was determined in plasma sampled at 3 AM in older male controls (n = 8) and in females (n = 10) at ovulation. The controls showed low or undetectable (less than 5 pg/ml) diurnal plasma melatonin levels and a very marked nocturnal rhythm (acrophase: 2.27 AM, mesor: 34.4 pg/ml, amplitude: 58.7 pg/ml). For the three control groups, no significant difference was observed in the nocturnal melatonin peak at 3 AM. The depressed patients also showed a significant melatonin rhythm but with lower amplitude (14.5 pg/ml) and mesor (19.1 pg/ml). The latter rhythm was not significantly phase-advanced with respect to the controls (acrophase at 1.18 and 2.34 AM, respectively). In 9 of the 11 patients, nocturnal melatonin secretion was less marked and frequently associated with hypercortisolemia. An additional episodic melatonin secretion was observed in the late afternoon in only two patients. In depressed patients, there was an increase in the mean cortisol secretion level (mesor at 13.6 micrograms/100 ml against 9.1 micrograms/100 ml in the controls), but the amplitude and the acrophase were not significantly modified. These data are discussed in terms of both the hypothalamus-pituitary-adrenal-epiphysis and aminergic abnormalities.     

Circadian secretion of cortisol and melatonin in cluster headache during active cluster periods and remission.

The cyclic nature of cluster headache warranted a study of the 24-hour rhythms of serum cortisol and melatonin. They were both altered during cluster periods as compared with periods of remission and healthy controls. The 24-hour mean and maximal cortisol levels were higher and the timing of the cortisol minimum was delayed as compared to the same patients in remission. Although there was no relation between the cortisol and melatonin levels and headaches, the rise of cortisol following many attacks might in part represent an adaptive response to pain. The nocturnal melatonin maximum was lower during cluster periods than in remission. This finding, and the dysautonomic signs during attacks, may reflect a change of the vegetative tone in a hyposympathetic direction.     

Abnormal secretion of melatonin and cortisol in relation to sleep disturbances in children with Williams syndrome

ObjectiveA high rate of sleep disturbances has been reported in individuals with Williams syndrome (WS) but the underlying aetiology has yet to be identified. Melatonin and cortisol levels display circadian rhythmicity and are known to affect and regulate sleep/wake patterns. The current study examined the levels of these two endocrine markers and explored a possible relationship with sleep patterns in children with WS.MethodsTwenty-five children with WS and 27 typically developing age- and gender-matched comparison children were recruited. Saliva was collected from each child at three time points: 4–6 pm, before natural bedtime, and after awakening. The levels of salivary melatonin and cortisol were analysed by specific enzyme-linked immunoassays. Sleep patterns were examined using actigraphy and the Children's Sleep Habit Questionnaire.ResultsThe WS group had shallower drops in cortisol and less pronounced increase in melatonin at bedtime compared to the controls. Furthermore, they also had significantly higher levels of cortisol before bedtime.ConclusionsIncreased bedtime cortisol and less pronounced rise in melatonin levels before sleep may play a role in the occurrence of sleep disturbances, such as delayed sleep onset, observed in children with WS. As both markers play a significant role in our circadian rhythm and sleep/wake cycle, it is necessary to examine sleep using multi-system analysis.     

顽固性原发性失眠症患者血浆皮质醇检测的临床意义

目的：检测顽固性原发性失眠症患者血浆皮质醇水平,评估其临床意义及对失眠症过度觉醒的预测价值。方法纳入顽固性原发性失眠症患者、原发性失眠症患者及正常睡眠人群各25例,分别检测清晨血浆皮质醇水平,并比较3组匹兹堡睡眠质量指数(PSQI)、过度觉醒量表(HAS)评分,及其评分与皮质醇水平的相关性。结果顽固性原发性失眠症患者的 PSQI、HAS 评分、血浆皮质醇水平均高于原发性失眠组和对照组,且血浆皮质醇水平与两量表总分及各因子分呈正相关。结论过度觉醒机制可能是失眠症发生的重要机制,血浆皮质醇可视为表征觉醒水平的重要指标。     

Characteristic changes in psychiatric symptoms, cortisol and melatonin but not prolactin in primary hyperparathyroidism

Psychiatric symptoms in primary hyperparathyroidism (PHPT) are usually characterized as depressive. In this study 13 patients with PHPT and six control patients with atoxic nodular goiter underwent psychiatric ratings with the comprehensive psychopathological rating scale (CPRS) the day before surgery. The 21 items in this scale were grouped into clusters. The ratings were repeated after successful removal of a parathyroid adenoma. Diurnal serum concentrations of cortisol, melatonin and prolactin were studied pre- and postoperatively in eight of the patients. Patients with PHPT had significantly higher CPRS total scores, 8.5 +/- 1.3, compared with goiter controls, 1.9 +/- 0.8, and showed a significant improvement of psychiatric symptoms after excision of the parathyroid adenoma, to 3.3 +/- 0.9. The preoperative diurnal and peak levels of cortisol and melatonin were higher (P less than 0.05) than after surgery. Serum melatonin fell to levels lower than those in healthy controls. Correlations were found between some clusters or items and cortisol or melatonin. Serum prolactin levels were normal and unaltered by parathyroid surgery. It is concluded that patients with PHPT show well defined psychiatric symptoms many of which are correlated to alterations in serum cortisol and melatonin accompanying PHPT. The improvement of symptoms seen after successful surgery further suggests that PHPT is associated with a specific psychiatric disorder similar to but distinguishable from major depressive disorder.     

Circadian rhythms of melatonin and cortisol in aging

The relationship of age to the circadian rhythms of melatonin and cortisol was investigated in 44 men and 27 women (age range 19-89 years). Subjects were physically and psychiatrically normal. Four hourly serial blood samples were drawn from 8:00 AM until 8:00 AM the next day, with additional samples at 10:00 PM and 2:00 AM. The indoor illumination was restricted to 300 lux during day and 50 lux during the night. Plasma melatonin and cortisol were estimated by radioimmunoassay. Results show that the means of melatonin and cortisol values decreased significantly with age when the subjects were divided into three age groups, i.e., 19-25 years, 42-65 years, and 66-89 years. They also showed a significant negative correlation with age. The acrophases of the two hormonal rhythms, however, showed different relationships to age. The acrophase of melatonin rhythm showed a positive correlation with age (r = 0.38, p less than 0.001), and cortisol showed a negative correlation with age (r = -0.56, p greater than 0.001). It is suggested that this may indicate a weakened responsiveness of the circadian system in the elderly to the day-night cycle and an altered relationship between the pacemakers driving melatonin and cortisol circadian rhythms. This may thus represent a biomarker for the intrinsic process of the aging of the brain.     

Treatment of primary insomnia with melatonin: a double-blind,placebo-controlled,crossover study

OBJECTIVE: To assess the hypnotic effect of melatonin in patients with primary insomnia. METHOD: Ten patients (mean age 50 yr, range 30-72 yr) who met the DSM-IV criteria for primary insomnia received, in random order, 0.3 mg of melatonin, 1.0 mg of melatonin or placebo 60 minutes before bedtime. A crossover design was used so that each patient received each of the 3 treatments for a 7-day period (with a 5-day washout period between). After each 7-day treatment, night time electroencephalographic (EEG) records were collected, and each morning, subjects completed sleep logs and analogue-visual scales to document the amount and subjective quality of sleep. RESULTS: There were no significant differences in sleep EEG, the amount or subjective quality of sleep or side effects between the placebo, 0.3-mg melatonin or 1.0-mg melatonin treatments. CONCLUSION: Melatonin did not produce any sleep benefit in this sample of patients with primary insomnia.     

Midwinter insomnia in the subarctic region: evening levels of serum melatonin and cortisol before and after treatment with bright artificial light

"Midwinter insomnia" (MI), mainly characterized by difficulties in falling asleep at night, is a common complaint during the period of obscuration or "dark period" north of the arctic circle. We hypothesize that MI is a result of a phase delay of the sleep-wake cycle due to insufficient exposure to daylight. In the present study based on this hypothesis, we wanted to find out whether otherwise healthy subjects with MI show abnormalities in the endocrine markers melatonin and cortisol late in the evening, and whether exposure to intensive light for one half hour in the morning for 5 days has any effect on the insomnia and on the endocrine variables. Nine subjects with typical MI were compared to eight controls. Before light exposure, the MI group had a significantly lower level of plasma melatonin in the evening than the controls, and a nonsignificant increase of plasma cortisol. After light exposure, the following results were seen in the MI group: sleep latency was moderately but significantly shortened, plasma melatonin increased to the same level as in the controls, and there was a nonsignificant increase of plasma cortisol. These results are largely in accordance with the predictions made from the phase delay hypothesis. However, other explanations cannot be ruled out.     

Nocturnal prolactin secretion in carpal tunnel syndrome

The correlation between plasma PRL levels and CTS was investigated in 21 patients in whom a specific causal agent of CTS could not be identified. No correlation between plasma PRL levels and other clinical and neurophysiological data was detected

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Sommario Il rapporto fra concentrazione plasmatica della PRL e sindrome del tunnel carpale è stata studiata in 21 pazienti con la forma idiopatica di tale sindrome. Non è stata trovata una correlazione fra i livelli di PRL e i dati clinici e neurofisiologici in questi pazienti.

     

Nocturnal melatonin profiles before and one year after beginning shift-work

Abstract Nocturnal serum melatonin profiles were determined twice for seven single women, during their time of employment as nurses (baseline), and after one year (follow up), in order to investigate the effects of shift-work on nocturnal melatonin secretion. All subjects were working in the same hospital under an irregularly rotating three-shift system. Five (5) mL blood samples were drawn six times at 2 h intervals between 20:00–06:00 hours under dim light conditions (< 50 lux). The same sampling procedures were repeated the following year. The results showed pronounced inter-individual differences in melatonin concentrations. There was a trend towards increasing maximum melatonin concentration (MAX melatonin) at follow up, with a similar tendency seen in summed melatonin (the sum of six measured melatonin concentrations). A trend was also seen towards increasing melatonin ratio at 06:00 hours (the percentage of melatonin concentration at 06:00 hours by summed melatonin) at follow up. Melatonin concentration at 06:00 hours was significantly higher at follow up, and a significant correlation between Morningness-Eveningness score (M-E score) at baseline and increased summed melatonin at follow up was also seen. These results suggest that: nocturnal melatonin secretion does not significantly increase after beginning shift-work; and that greater increases in melatonin secretion at follow up are found in subjects with higher M-E scones (increased morning type). With more subjects, however, there may be significant increase in MAX melatonin and/or summed melatonin in the follow-up study.