Circadian rhythms of melatonin,cortisol and prolactin in patients with obsessive-compulsive disorder

Plasma melatonin, cortisol and prolactin (PRL) levels were measured over a 24-h period in 13 drug-free patients with obsessive-compulsive disorder and in matched healthy subjects. The circadian profiles of melatonin and PRL were altered in patients; the circadian rhythm of cortisol was preserved, although at a higher level compared with normal controls. These changes were significantly related to the severity of the obsessive-compulsive symptoms. Further studies need to clarify the state- or trait-dependent character of these abnormalities.     

Effect of lysine vasopressin in depressed patients on mood and 24-hour rhythm of growth hormone, cortisol, melatonin and prolactin

Lysine-8-vasopressin (LVP) for 10 days and in doses up to 13.5 LVP units did not significantly alter the Hamilton Depression Rating Scale scores of 12 severely depressed, treatment-resistant patients who were evaluated in a double-blind crossover study. The 24-h rhythms of melatonin, cortisol, growth hormone and prolactin appeared remarkably stable over the course of repeated measurement. LVP administration did not affect these 24-h rhythms.     

Morphine inhibits cortisol and stimulates prolactin secretion in man

The role of opioids in endocrine regulation has been the subject of numerous studies. Surprisingly, however, the acute endocrine effects of morphine on basal hormonal levels in man have not been adequately documented. We report here the effects of intravenous morphine (5 mg) on plasma cortisol and prolactin. Fourteen healthy volunteers (nine male, five female) received morphine at 0930 hr. Blood samples were collected immediately before and 30, 60, 90, 120 and 180 min after the injection. In six of the male subjects the procedure was repeated with a placebo (normal saline) injection. Morphine stimulated prolactin release. There was a trend for a greater response in females compared to male subjects. Cortisol secretion was markedly suppressed by morphine. In sharp contrast to the results obtained with placebo, cortisol levels following morphine declined progressively at a rate consistent with the half-life of cortisol. This downward trend of cortisol values continued uninterrupted for the duration of the experiment in all 14 subjects. These results are consistent with the presence of an inhibitory opioid mechanism in the human hypothalamopituitary-adrenal axis.     

Seasonal changes in circadian peripheral plasma concentrations of melatonin, serotonin, dopamine and cortisol in aged horses with Cushing's disease under natural photoperiod

Equine pituitary pars intermedia dysfunction (PPID) is a common and serious condition that gives rise to Cushing's disease. In the older horse, it results in hyperadrenocorticism and disrupted energy metabolism, the severity of which varies with the time of year. To gain insight into the mechanism of its pathogenesis, 24-h profiles for peripheral plasma melatonin, serotonin, dopamine and cortisol concentrations were determined at the winter and summer solstices, and the autumn and spring equinoxes in six horses diagnosed with Cushing's disease and six matched controls. The nocturnal rises in plasma melatonin concentrations, although different across seasons, were broadly of the same duration and similar amplitude in both groups of animals (P > 0.05). The plasma concentrations of cortisol did not show seasonal variation and were different in diseased horses only in the summer when they were higher across the entire 24-h period (P < 0.05). Serotonin concentrations were not significantly affected by time of year but tended to be lower in Cushingoid horses (P = 0.07). By contrast, dopamine output showed seasonal variation and was significantly lower in the Cushing's group in the summer and autumn (P < 0.05). The finding that the profiles of circulating melatonin are similar in Cushingoid and control horses reveals that the inability to read time of year by animals suffering from Cushing's syndrome is an unlikely reason for the disease. In addition, the results provide evidence that alterations in the dopaminergic and serotoninergic systems may participate in the pathogenesis of PPID.     

Sex-linked differences in cortisol, ACTH and prolactin responses to 5-hydroxy-tryptophan in healthy controls and minor and major depressed patients

Some researchers have found that the administration of 5-hydroxytryptophan (5-HTP) results in increased cortisol secretion in major depressives but not in healthy controls. Other authors observed gender-related differences in cortisol responses to 5-HTP in major depressives. In order to investigate the pituitary/adrenal responsivity to 5-HTP, the authors measured cortisol, adrenocorticotropic hormone (ACTH) and prolactin (PRL) in 30 healthy controls and in 90 depressed patients; the hormone levels were determined in baseline conditions and 60, 90 and 120 min after 125 mg L-5-HTP (orally, non-enteric coated). We found that healthy men had significantly higher cortisol responses to L-5-HTP than healthy women. In the major depressives with melancholia and/or psychotic features these differences were reversed: women exhibited significantly higher cortisol and PRL responses than men. In the female group the most severely depressed patients had increased cortisol and PRL responses to L-5-HTP. The amplitudes of the cortisol, ACTH and PRL responses to L-5-HTP were significantly and positively correlated. It was concluded that the central serotonergic regulation of ACTH and PRL is significantly different between the sexes and between healthy controls, minor depressives and severely depressed patients.     

Effects of propantheline bromide on basal growth hormone,cortisol and prolactin levels

Propantheline bromide, a peripheral anticholinergic drug with muscarinic and nicotinic blocking properties, was given by mouth to normal young men. Propantheline (45 mg) significantly lowered basal growth hormone concentrations at 0800 hr, 12 hr after administration. Propantheline (30 mg) tended (p = 0.08) to lower growth hormone concentrations at 1200 hr, 16 hr after administration. Cortisol and prolactin levels were not changed 12, 16 and 20 hr after propantheline (30 mg) nor 12 hr after propantheline (45 mg).     

Interferon-alpha-induced depressive symptoms are related to changes in the cytokine network but not to cortisol

OBJECTIVE: Proinflammatory cytokines have the potential to activate the hypothalamo-pituitary-adrenocortical (HPA) axis, and HPA axis hyperactivity is also encountered in depression. Therefore, the induction of depressive symptoms by interferon-alpha (IFN-alpha) may be mediated by changes in the cytokine network and the HPA axis. METHODS: In 17 hepatitis C patients undergoing IFN-alpha treatment, depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS). In addition, serum cytokine concentrations were measured. Saliva was collected five times over the course of a day in order to assess daily average cortisol (DAC) and awakening response. Assessments were carried out at baseline and six later time points after starting treatment. RESULTS: During treatment, the increases in the MADRS were significantly and positively correlated with soluble interleukin (IL)-2 receptor, tumor necrosis factor alpha (TNF-alpha), and IL-6. There were no significant associations between the DAC or cortisol awakening response with the MADRS score. CONCLUSION: Results suggest a clear connection between IFN-alpha-induced depressive symptoms and cytokine concentrations, but not cortisol.     

Melatonin does not inhibit hypothalamic-pituitary-adrenal activity in waking young men

The pineal hormone melatonin is mainly secreted during night-time which, in humans, is the normal time of sleep. It has been proposed that, during this period, melatonin exerts an inhibitory influence on secretory activity of the hypothalamic-pituitary-adrenal (HPA) system, although there is little evidence for this view in humans. In blind humans, a single oral dose of melatonin at bed time suppressed nocturnal cortisol secretion. However, suppression could have been secondary to an improved sleep after melatonin in these experiments. In the present study, we examined whether melatonin exerts a similar inhibitory effect on HPA activity in waking subjects. Fourteen healthy young men were tested at bed time, but kept awake throughout the experimental epoch. Thirty minutes after oral ingestion of 5 mg melatonin, activity of the HPA-system was stimulated through a standard insulin-induced hypoglycaemia. Adrenocorticotrophin hormone and cortisol concentrations under basal conditions before insulin injection, as well as in response to insulin-induced hypoglycaemia, were almost identical for the melatonin and placebo control conditions (P > 0.5). However, melatonin increased plasma prolactin concentrations (P < 0.01) and reduced systolic blood pressure in the time interval following hypoglycaemia (P < 0.05). Based on a review of the literature and our results, we conclude that melatonin per se has no substantially suppressing effect on HPA secretory activity, although such an effect can be gated by sleep-related processes.     

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.     

Testosterone, cortisol, prolactin and bioactive luteinizing hormone in day and night samples of cerebrospinal fluid and serum of male rhesus monkeys

Testosterone (T), cortisol (C), prolactin (PRL) and bioactive luteinizing hormone (bLH) were found to be normal constituents of the cerebrospinal fluid (CSF) of all the 15 adult male rhesus monkeys studied. The CSF levels of the hormones showed a good correlation with their serum levels. The geometric mean values of circulating levels of T, PRL, bLH in all the animals studied were significantly lower iin the samples of the two body fluids collected between 09.00 and 11.00 h as compared with those collected between 21.00 and 23.00 h. C levels were higher during the day as compared with the night samples. This marked difference between the day and night levels of the circulating hormones was not observed in a few individuals which suggests that the diurnal changes in circulating levels of these hormones may occur as a rule in all rhesus monkeys. The serum:CSF ratios for C, PRL and bLH did not vary significantly between the day and night samples of the body fluids as they did for T. This suggests that T is poorly transferred from the blood to the CSF as compared with the other 3 hormones studied. The possible pathways by which the hormones are transferred into the CSF and the functional significance of their presence in the CSF are discussed.     

Effects of electroconvulsive therapy on neuropsychological function and circulating levels of ACTH, cortisol, prolactin, and TSH in patients with major depressive illness

Thirteen patients with major depressive illness received unilateral electroconvulsive therapy (ECT). Memory and some other neuropsychological functions were studied concomitantly with changes in clinical symptoms. ACTH in plasma and cortisol, prolactin (PRL) and TSH in serum were measured 30 min before and 1, 5, 15, 30 and 60 min after treatment. Memory functions, impaired after the ECT series, were completely regained 1 month later. ACTH, cortisol, PRL and TSH were significantly increased by ECT. The maximum hormone level after ECT was lower at the last ECT in the series as compared with the first. After the last treatment, nonverbal memory performance was negatively associated with the maximum ACTH level after ECT and verbal learning was negatively correlated to the maximum cortisol level. The reason for these relationships is not known. Since both the ACTH secretion and memory function may be dependent upon the intracerebral catecholamines, the present findings may reflect variations in central monoaminergic receptor function.     

An interaction between the pineal gland and olfactory deprivation in potentiating the effects of melatonin on gonads,accessory sex organs,and prolactin in male rats

Male rats (25–26 days of age) housed with 14 hours of light per day (lights on 0600–2000 hours) were either olfactory bulbectomized (rendering them anosmic), bulbectomized plus pinealectomized (Pinx), or left intact. On the day following the operations, intact, anosmic, and anosmic-Pinx animals began receiving single, daily afternoon (1700–1800 hours) subcutaneous injections of 50 μg of melatonin (MEL) for six weeks, while an additional group of intact controls received injections of diluent. At the end of this period, body, anterior pituitary, testicular, and seminal vesicle weights were significantly reduced in intact-MEL-treated animals. Anosmic animals that had been treated with MEL experienced a further, highly significant, 65%, 90%, and 85% depression in testicular, seminal vesicle, and ventral prostate weights, respectively, as compared with intact control and MEL-treated rats. Additionally, both body and anterior pituitary weights were significantly decreased in MEL-treated, anosmic rats. Anosmic-Pinx rats treated with MEL had organ and body weights that were intermediate between those of intact-MEL and anosmic-MEL-treated animals. Pituitary and serum levels of prolactin (Prl) were significantly lower in anosmic-MEL-treated rats than in intact or intact-MEL-treated groups. Similarly, Prl levels were depressed in the anosmic-Pinx rats treated with MEL; however, serum Prl was not statistically lower than in intact or intact-MEL-treated animals. These results indicate that anosmic male rats have an increased sensitivity to antigonadotrophic and Prl-inhibitory effects of MEL. Furthermore, the data suggest that the presence of the pineal gland in anosmic rats is important in permitting anosmia maximally to sensitize the neuroendocrine-reproductive axis to the antigonadotrophic effects of exogenously administered MEL.     

Noradrenaline and dopamine regulation of prolactin secretion in sheep: role in prolactin homeostasis but not photoperiodism

The role of noradrenaline (NA) and dopamine (DA) in the hypothalamic control of prolactin (PRL) secretion was investigated in hypothalamic intact (control) and hypothalamo-pituitary disconnected (HPD) Soay rams. The animals were exposed to alternating 16-weekly periods of short (8 L : 16D) and long days (16 L : 8D) to induce marked cyclical changes in PRL secretion in both groups (as demonstrated previously). Selective NA and DA receptor antagonists (dose: 1.2 micromol/kg) were administered under short days (low endogenous PRL secretion), and agonists (dose: 0.0012-0.12 micromol/kg) were administered under long days (high endogenous PRL secretion). The acute changes in blood PRL concentrations were measured over 4 h as the index of responsiveness. Under short days, treatment with WB4101 (alpha-1 adenoceptor antagonist), and rauwolscine (alpha-2 antagonist), consistently increased PRL secretion in control, but not in HPD rams. The treatments produced similar acute, drug-specific behavioural effects in both groups. Propranolol (beta antagonist) had no effect on PRL secretion, while sulpiride (DA D-2 antagonist) induced a marked increase in blood PRL concentrations in control rams (> 4 h), and a transient effect in HPD rams (15 min). Under long days, when endogenous PRL secretion was increased, phenylephrine (alpha-1 agonist) produced no effects, while bromocriptine (DA D-2 agonist) robustly decreased PRL concentrations in both control and HPD rams, even at the lowest treatment dose. Overall, the positive responses to the antagonists in the control rams, support the view that DA (acting via D-2 receptors), and to a lesser extent NA (acting via alpha-1/alpha-2 receptors), negatively regulate PRL secretion. In contrast, the lack of responses to the antagonists in the HPD rams, support the view that neither DA, nor NA, mediate the photoperiodic control of PRL secretion.     

Catecholamine mechanisms in medio-basal hypothalamus influence prolactin but not growth hormone secretion

Medio-basal hypothalamic (MBH) catecholamine mechanisms in the regulation of prolactin and growth hormone (GH) secretion were investigated in unanesthetized rats with chronic indwelling venous cannulae and bilateral MBH directed intracerebral guide cannulae.MBH injections of the catecholamine-specific neurotoxin 6-hydroxydopamine (6-OHDA; 2 μg based in 0.5 μl 0.9% saline) had no effect upon basal prolactin or GH secretion. Examination of catecholamine fluorescence indicated that MBH 6-OHDA treatment produced widespread disruption of MBH catecholamine afferents but did not destroy tuberoinfundibular dopamine neurons of the arcuate nucleus, nor median eminence catecholamine structures.MBH injections (0.5 μl, 0.032 M solutions) of dopamine, noradrenaline or adrenaline all produced statistically significant increases in plasma prolactin levels. The potency of these 3 catecholamines in evoking prolactin release differed markedly, adrenaline having the greatest effect. MBH catecholamine injections had no effect upon plasma GH levels compared to saline injected controls.The present data suggest that MBH catecholamine afferents are unimportant in the regulation of basal patterns of GH or prolactin secretion. As MBH catecholamine injections stimulate prolactin release this region may contain a prolactin-facilitatory catecholamine mechanism which is capable of generating prolactin surges in response to certain environmental or endogenous stimuli.     

Serum prolactin, psychopathology, and ventricular size in chronic schizophrenia

Previous reports have suggested an inverse relationship between serum prolactin concentrations and psychopathology in schizophrenic patients. One such study noted this relationship to be particularly robust in schizophrenic patients with normal as compared to enlarged ventricles, as determined by computed tomography (Kleinman et al., 1982). Because of the potential implications of these findings for the dopamine hypothesis of schizophrenia, we reexamined this issue in 23 schizophrenic patients diagnosed according to Research Diagnostic Criteria. We could find no significant correlation between serum prolactin concentration and psychopathology assessed by either Brief Psychiatric Rating Scale or the Schedule for Affective Disorders and Schizophrenia, Change Form. The lack of a significant relationship was noted in patients with normal or enlarged ventricles. Possible reasons for the discrepancies between our findings and previous reports are discussed.     

Experimental jetlag disrupts circadian clock genes but improves performance in racehorses after light-dependent rapid resetting of neuroendocrine systems and the rest-activity cycle

Abrupt alterations in the 24-h light : dark cycle, such as those resulting from transmeridian air travel, disrupt circadian biological rhythms in humans with detrimental consequences on cognitive and physical performance. In the present study, a jetlag-simulated phase shift in photoperiod temporally impaired circadian peaks of peripheral clock gene expression in racehorses but acutely enhanced athletic performance without causing stress. Indices of aerobic and anaerobic capacities were significantly increased by a phase-advance, enabling prolonged physical activity before fatigue occurred. This was accompanied by rapid re-entrainment of the molecular clockwork and the circadian pattern of melatonin, with no disturbance of the adrenal cortical axis, but a timely rise in prolactin, which is a hormone known to target organs critical for physical performance. Subsequent studies showed that, unlike the circadian pattern of melatonin, and in contrast to other species, the daily rhythm of locomotor activity was completely eliminated under constant darkness, but it was restored immediately upon the reintroduction of a light : dark cycle. Resetting of the rhythm of locomotion was remarkably fast, revealing a rapid mechanism of adaptation and a species dependency on light exposure for the expression of daily diurnal activity. These results show that horses are exquisitely sensitive to sudden changes in photoperiod and that, unlike humans, can benefit from them; this appears to arise from powerful effects of light underlying a fast and advantageous process of adjustment to the phase shift.     

Salivary cortisol and psychopathology in children bereaved by the september 11, 2001 terror attacks.

BACKGROUND: Studies suggest that stressful events increase risk for childhood anxiety and depression and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This prospective longitudinal study evaluated relationships among severe psychosocial stress, psychiatric morbidity, and HPA axis function in children. METHODS: Forty-five children (mean age: 8.9 +/- 2.9 years) suffering parent death from September 11, 2001 terror attacks and 34 nonbereaved children (mean age: 9.3 +/- 2.5 years) were evaluated prospectively at 6-month intervals in this 2-year study. Assessments involved diagnostic interviews (Child Schedule for Affective Disorders and Schizophrenia [K-SADS]) for psychopathology and 3 days of baseline salivary cortisol and a salivary dexamethasone suppression test for HPA axis function. RESULTS: Bereaved children, but not nonbereaved children, had significantly increased rates of psychiatric disorders involving anxiety disorders, especially posttraumatic stress disorder (PTSD), after September 11, 2001 compared with retrospective assessments before September 11, 2001. Morning (AM) and 4:00 pm baseline cortisol were significantly and persistently higher for bereaved than nonbereaved children. Compared with bereaved children without psychopathology, bereaved children with PTSD had significantly lower 4:00 pm baseline cortisol and significantly greater 4:00 pm cortisol suppression. Children with generalized anxiety disorder had significantly less AM cortisol suppression than children without psychopathology. CONCLUSIONS: Children bereaved by sudden, unexpected parent death had persistent psychological dysfunction and HPA axis dysregulation in this study.     

精神分裂症患者的焦虑抑郁症状与血浆皮质醇水平观察

目的观察不同病期精神分裂症患者的焦虑抑郁症状与血浆皮质醇水平的变化及两者的关系。方法以精神分裂症患者60例为研究组,于治疗前0周、治疗后2周末和4周末应用汉密顿焦虑量表（HAMA）和汉密顿抑郁量表（HAMD）分别评定患者发病期和好转期的焦虑抑郁症状,并同步测定血浆皮质醇水平,观察其焦虑抑郁程度与血浆皮质醇水平变化及分析两者的关系,同时与30名健康者作对照。结果研究组的HAMA和HAMD总分在发病期（0周和2周末）和好转期（第4周末）均显著高于正常对照组（P〈0.05或P〈0.01）;研究组的血浆皮质醇水平在发病期显著升高（P〈0.01）,随着病情的好转而恢复正常;研究组血浆皮质醇水平的变化（0周与2周末,2周末与4周末）与HAMA、HAMD总分的变化无显著相关性（P〉0.05）。结论精神分裂症患者在不同病期均可出现焦虑抑郁症状,发病期伴有血浆皮质醇水平升高,但焦虑抑郁症状与血浆皮质醇水平无明显关联。     

Plasma levels of beta-endorphin, cortisol, prolactin and growth hormone in depressed patients

Basal serum cortisol, growth hormone, prolactin and immunoreactive (IR) plasma beta-endorphin levels were measured in 31 depressed patients (14 endogenous, 17 nonendogenous) undergoing the dexamethasone suppression test. The endogenously depressed patients had significantly higher (22.55 +/- 1.34 micrograms/dl) predexamethasone cortisol levels than the nonendogenous patients (16.34 +/- 1.93 micrograms/dl). The mean serum prolactin and growth hormone values of these two groups were not significantly different, while plasma IR-beta-endorphin levels of the endogenous group (40.11 +/- 3.57 pg/ml) were significantly lower than those of the nonendogenous group (120.33 +/- 27.98 pg/ml). Neither group showed a significant correlation between plasma IR-beta-endorphin and serum cortisol values. These results indicate that measurement of predexamethasone serum cortisol values and plasma IR-beta-endorphin could be valuable laboratory tests in the diagnosis of depression.