RESUMEN
INTRODUCTION: Neuroendocrine changes in depression have long been recognized, with a focus mainly on hypercortisolism. The other hormone of the hypothalamus-pituitary adrenocortical system, aldosterone, has been widely neglected. METHODS: Here we summarize the involvement of the renin-angiotensin-aldosterone system (RAAS) and the regulation of aldosterone in health with a particular focus on sleep-related changes and its role in stress-related conditions, like major depression. RESULTS: We highlight its role in functional systems which could be relevant in the therapy for refractory depression, like inflammatory mechanisms, the monoaminergic and the glutamatergic systems. Furthermore, anatomic areas which specifically mediate the action of aldosterone have been identifi ed. In particular the nucleus of the solitary tract (NTS) seems to have an important role and appears to be a target for antidepressive manipulations, like vagus nerve stimulation. Clinical data demonstrating the efficacy of aldosterone-reducing strategies for specific depressive syndromes are reviewed. DISCUSSION: In particular aspects of differentiation between melancholic vs. atypical depression spectrum disorders are discussed.
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Depresión/fisiopatología , Hormonas/fisiología , Sistema Renina-Angiotensina/fisiología , Trastornos del Sueño-Vigilia/fisiopatología , Estrés Psicológico/fisiopatología , HumanosRESUMEN
OBJECTIVE: This multicenter, cross-sectional study was conducted to determine the sensitivity and specificity of a 9-item Wearing-off Questionnaire (WOQ-9) compared with assessment by a clinician. METHODS: Patients with a diagnosis of Parkinson's disease (PD) for 5
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Evaluación de la Discapacidad , Resistencia a Medicamentos/fisiología , Evaluación de Resultado en la Atención de Salud , Enfermedad de Parkinson/fisiopatología , Encuestas y Cuestionarios , Anciano , Antiparkinsonianos/uso terapéutico , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/tratamiento farmacológico , Estudios Retrospectivos , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
Bidirectional interactions between nocturnal hormone secretion and sleep regulation are well established. In particular, a link between PRL and rapid eye movement (REM) sleep has been hypothesized. Short-term administration of PRL and even long-term hyperprolactinemia in animals increases REM sleep. Furthermore, sleep disorders are frequent symptoms in patients with endocrine diseases. We compared the sleep electroencephalogram of seven drug-free patients with prolactinoma (mean PRL levels 1450 +/- 1810 ng/mL; range between 146 and 5106 ng/mL) with that of matched controls. The patients had secondary hypogonadism but no other endocrine abnormalities. They spent more time in slow wave sleep than the controls (79.4 +/- 54.4 min in patients vs. 36.6 +/- 23.5 min in controls, P < 0.05). REM sleep variables did not differ between the samples. Our data suggest that chronic excessive enhancement of PRL levels exerts influences on the sleep electroencephalogram in humans. Our result, which seems to be in contrast to the enhanced REM sleep under hyperprolactinemia in rats, leads to the hypothesis that both slow wave sleep and REM sleep can be stimulated by PRL. These findings are in accordance with reports of good sleep quality in patients with prolactinoma, which is in contrast to that of patients with other endocrine diseases.
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Neoplasias Hipofisarias/fisiopatología , Prolactinoma/fisiopatología , Fases del Sueño/fisiología , Sueño/fisiología , Adulto , Animales , Electroencefalografía , Femenino , Humanos , Hipogonadismo/etiología , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/complicaciones , Prolactina/sangre , Prolactinoma/complicaciones , Ratas , Sueño REM/fisiología , Factores de TiempoRESUMEN
Aging is accompanied by a continuous decline in slow wave sleep (SWS) and in growth hormone (GH) secretion, particularly during the sleeping period. Because short-term pulsatile administration of cortisol increases GH release and SWS in young adults, we wondered whether similar effects can be induced also in elderly men. Hourly injections of cortisol between 1700 and 600 h increased stage 2 and SWS and decreased rapid eye movement sleep. Spectral analysis revealed significant increases in delta and theta power. Cortisol infusions increased the GH secretion prior to sleep onset, but remained largely unchanged during sleep. Thus, sleep EEG and GH release are modulated by cortisol administration in a manner similar to that in young subjects, but to a lesser extent. The stimulatory effect of cortisol on both GH release and SWS points to a mechanism involving glucocorticoid-enhanced production and release of GH-releasing hormone that activates pituitary GH release and simultaneously antagonizes the effects of corticotropin-releasing hormone and somatostatin.
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Envejecimiento/fisiología , Hormona de Crecimiento Humana/sangre , Hidrocortisona/farmacología , Sueño/efectos de los fármacos , Adulto , Anciano , Envejecimiento/sangre , Ritmo Delta/efectos de los fármacos , Electroencefalografía/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sueño/fisiología , Fases del Sueño/efectos de los fármacos , Ritmo Teta/efectos de los fármacos , Vigilia/efectos de los fármacosRESUMEN
Aging is associated with decreased sleep continuity, slow wave sleep (SWS), growth hormone (GH) release and an increased hypothalamo-pituitary-adrenocortical (HPA) system activity. Total sleep deprivation (TSD) is a strong stimulus for sleep. To determine if aging affects the response to TSD, for the first time the combined effects of TSD on conventional and spectral sleep electroencephalographic (EEG) parameters and GH, cortisol and prolactin secretion were compared in elderly (60-80 years; n = 7) vs. younger subjects (20-30 years; n = 7). MANOVA revealed a reduction of SWS in the elderly. TSD led to an increase in SWS, a decrease in sleep onset latency, rapid eye movement (REM) density and by trend REM-latency without a global group difference. GH was reduced, whereas prolactin was enhanced in the elderly. After TSD GH was unchanged and prolactin secretion was enhanced without group difference. Thus, the plasticity of the sleep-endocrine system in response to TSD is sustained during aging. The possible involvement of the GABAergic system, that seems not to be severely impaired with age, is proposed.
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Envejecimiento/fisiología , Encéfalo/fisiología , Sistema Endocrino/fisiopatología , Privación de Sueño/fisiopatología , Sueño/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción/fisiologíaRESUMEN
With increasing age, sleep becomes more shallow and fragmented and sleep-associated growth hormone (GH) release declines. GH secretion is regulated physiologically by opposite actions of GH-releasing hormone (GHRH) and somatostatin (SRIF). The administration of GHRH promotes sleep in both young and elderly controls, whereas SRIF does not induce sleep-EEG changes in young subjects. Because the influence of peripheral SRIF administration on sleep EEG in the elderly is unknown, we administered 50 micrograms SRIF-14 every hour between 2200 and 0100 hours to controls with an age range from 60 to 73 years (mean +/- SD 67.4 +/- 5.1 years). After SRIF administration, total sleep time and rapid eye movement (REM) sleep decreased significantly, and more time was spent awake in the first sleep cycle, suggesting that SRIF induces sleep deterioration in the elderly. The peptide may become more effective on sleep EEG in older than in younger subjects, because of the decline of GHRH-GH axis activity, which may contribute to sleep disturbances in aging. The increased efficacy of SRIF in the elderly also may be explained by enhanced leakage of the blood-brain barrier.
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Sueño/efectos de los fármacos , Somatostatina/efectos adversos , Anciano , Método Doble Ciego , Electroencefalografía/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sueño/fisiología , Fases del Sueño/efectos de los fármacos , Fases del Sueño/fisiología , Sueño REM/efectos de los fármacos , Sueño REM/fisiología , Somatostatina/fisiologíaRESUMEN
The long-acting somatostatin (SRIF) analogue octreotide decreased nonrapid eye movement sleep (NREMS) in the rat. This effect is opposite to the promotion of sleep after growth hormone (GH)-releasing hormone (GHRH) in various species including humans. Therefore, it appears likely that GHRH and SRIF, besides their opposite action on pituitary GH release, interact reciprocally in sleep regulation. In previous studies, SRIF impaired sleep in elderly subjects, although sleep in young men remained unchanged. We hypothesized that octreotide is a useful tool to study the role of SRIF in human sleep regulation. We examined the effect of subcutaneous administration of 0.1 mg octreotide at 2245 on the sleep EEG of seven young male controls (age, mean+/-SD, 22.3+/-3.0 years). In comparison to placebo, octreotide administration prompted decreases of sleep stage 4 during the total night and of rapid eye movement sleep (REMS) density during the first half of the night. Intermittent wakefulness increased during the second half of the night. The spectral analysis of total night NREMS revealed a significant decrease of sigma power. Similar to the effect of the short-acting SRIF in the elderly, the long-acting SRIF analogue octreotide impaired sleep in young healthy subjects. Obviously, the influence of octreotide on sleep is superior to that of short-acting SRIF, which did not affect sleep in young men. We suggest a reciprocal interaction of GHRH and SRIF in sleep regulation.
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Electroencefalografía/efectos de los fármacos , Octreótido/farmacología , Trastornos del Sueño-Vigilia/inducido químicamente , Adolescente , Adulto , Método Doble Ciego , Humanos , Masculino , Octreótido/efectos adversos , Fases del Sueño/efectos de los fármacos , Somatostatina/análogos & derivados , Factores de TiempoRESUMEN
Tianeptine enhances while paroxetine inhibits serotonin reuptake into neurons; however, both show an antidepressive action. A subgroup of 38 depressed patients from a drug trial comparing the efficacy of tianeptine with that of paroxetine was studied with regard to their effects on sleep regulation, especially in relation to treatment response. We recorded sleep EEGs at day 7 and day 42 after the start of treatment with either compound, which allows measurement of changes due to the antidepressive medication in relation to the duration of treatment. Spectral analysis of the non-REM sleep EEG revealed a strong decline in the higher sigma frequency range (14-16 Hz) in male treatment responders independent of medication, whereas nonresponders did not show marked changes in this frequency range independent of gender. The patients receiving paroxetine showed less REM sleep and more intermittent wakefulness compared to the patients receiving tianeptine. REM density after 1 week of treatment was a predictor of treatment response in the whole sample. Psychopathological features with regard to the score in single items of the HAMD revealed predictive markers for response, some of which were opposite in the gender groups, especially those related to somatic anxiety. Changes in REM density were inversely correlated to the changes in HAMD in the paroxetine, but not the tianeptine, group. Our data suggest the importance of taking gender into account in the study of the biological effects of drugs. The study further points to the importance of the higher sigma frequency range in the sleep EEG of non-REM sleep and REM density as a marker of treatment response.
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Trastorno Depresivo Mayor/tratamiento farmacológico , Electroencefalografía/efectos de los fármacos , Paroxetina/uso terapéutico , Sueño/fisiología , Tiazepinas/uso terapéutico , Adulto , Anciano , Análisis de Varianza , Biomarcadores , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/psicología , Electroencefalografía/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paroxetina/farmacología , Pacientes/estadística & datos numéricos , Factores Sexuales , Sueño/efectos de los fármacos , Tiazepinas/farmacologíaRESUMEN
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.
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Hormona Adrenocorticotrópica/efectos de los fármacos , Hidrocortisona/sangre , Neuropéptido Y/farmacología , Fases del Sueño/efectos de los fármacos , Hormona Adrenocorticotrópica/sangre , Adulto , Apetito/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Ritmo Circadiano , Electroencefalografía , Hormona del Crecimiento/sangre , Hormona del Crecimiento/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Inyecciones Intravenosas , Leptina/sangre , Masculino , Prolactina/sangre , Prolactina/efectos de los fármacos , Fases del Sueño/fisiologíaRESUMEN
Aging and menopause are associated with alterations of the sleep EEG, while age-related changes of the hypothalamo-pituitary-adrenal (HPA) axis remain controversial. Major depression is also associated with typical sleep-endocrine changes, including enhanced activity of the HPA axis, while an influence of age and gender on these alterations is less clear. To test the hypothesis that after menopause sleep-endocrine alterations associated with major depression are accentuated, we examined the sleep EEG and nocturnal hormone secretion (ACTH, cortisol, GH, estradiol, LH, FSH, and leptin) in 16 drug-free female patients, mostly with the first episode of a major depressive disorder (seven pre- and nine postmenopausal subjects) and 19 female controls (10 subjects in the early follicular phase and nine postmenopausal subjects). Nocturnal cortisol secretion was increased in postmenopausal patients with depression, while a decrease was noted in postmenopausal controls. Sleep alterations typically associated with depression, namely a reduction in sleep continuity and slow wave sleep (SWS) and an increase in REM density, were prominent in post- but not in premenopausal patients. An inverse correlation was noted between the decline in SWS and sleep continuity and FSH secretion in patients with depression, suggesting a role of menopause for these sleep-endocrine alterations typically associated with major depression. In contrast, in premenopausal patients we noted primarily a shift in SWS and delta-EEG activity from the first to the second non-REM period, which was not related to age or hormone secretion. Though the relatively small number of subjects per group precludes a definitive conclusion, our data open up the possibility that the sleep-endocrine changes typically associated with major depression are most prominent in postmenopausal patients. Whether the predominant alteration of the distribution of SWS and delta EEG activity in younger patients with a first episode of major depression has a predictive value for the future course of the disease remains to be investigated.
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Trastorno Depresivo Mayor/fisiopatología , Hidrocortisona/sangre , Menopausia/fisiología , Hormonas Adenohipofisarias/sangre , Trastornos del Sueño-Vigilia/fisiopatología , Hormona Adrenocorticotrópica/sangre , Adulto , Anciano , Trastorno Depresivo Mayor/complicaciones , Electroencefalografía , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Hormona de Crecimiento Humana/sangre , Humanos , Leptina/sangre , Hormona Luteinizante/sangre , Análisis por Apareamiento , Menopausia/psicología , Persona de Mediana Edad , Polisomnografía , Trastornos del Sueño-Vigilia/complicaciones , Sueño REM/fisiología , Estadística como AsuntoRESUMEN
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.
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Hormona Adrenocorticotrópica/metabolismo , Electroencefalografía/efectos de los fármacos , Hormona de Crecimiento Humana/metabolismo , Hidrocortisona/metabolismo , Oligopéptidos/farmacología , Administración Intranasal , Administración Oral , Administración Sublingual , Adulto , Humanos , Inyecciones Intravenosas , Masculino , Oligopéptidos/administración & dosificación , Sueño REM/efectos de los fármacos , Factores de TiempoRESUMEN
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.
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Hormona Adrenocorticotrópica/sangre , Ritmo Delta , Electroencefalografía/efectos de los fármacos , Sulfato de Magnesio/administración & dosificación , Fases del Sueño/efectos de los fármacos , Adulto , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Hormona de Crecimiento Humana/sangre , Humanos , Hidrocortisona/sangre , Infusiones Intravenosas , Masculino , Melatonina/sangre , Polisomnografía , Prolactina/sangre , Receptores de GABA-A/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidoresRESUMEN
RATIONALE: EMD 68843 (EMD) has properties of a serotonin (5-HT)-reuptake inhibitor and a partial 5-HT1A agonist in one molecule in order to combine antidepressive and anxiolytic properties. OBJECTIVE: We investigated the effects of EMD on the sleep EEG in order to characterize how the complex interaction between these two properties influences the sleep EEG. METHODS: We performed a randomized crossover study in ten young normal male controls (20-30 years), receiving a single dose of 20 mg EMD or placebo orally at 2100 hours. Sleep EEG was recorded from 2300 to 0700 hours. RESULTS: After EMD, rapid eye movement (REM) sleep was nearly totally abolished. In the course of the night other effects on the sleep EEG occurred in distinct intervals. Slow wave sleep and EEG delta power increased in the first and third one-third of the night, whereas wakefulness was enhanced in the second and third one-third of the night. CONCLUSION: The sleep EEG effects of EMD fit with its pharmacological profile, which might lead to adaptive changes suggested to characterize an antidepressive substance.
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Benzofuranos/farmacología , Electroencefalografía/efectos de los fármacos , Indoles/farmacología , Receptores de Serotonina/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Agonistas de Receptores de Serotonina/farmacología , Adulto , Benzofuranos/efectos adversos , Estudios Cruzados , Método Doble Ciego , Humanos , Indoles/efectos adversos , Masculino , Piperazinas , Receptores de Serotonina 5-HT1 , Agonistas de Receptores de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Factores de Tiempo , Clorhidrato de VilazodonaRESUMEN
The sigma (sigma) receptor has been proposed as a target of neuroleptic drugs. Preclinical data suggest that panamesine (EMD 57445), a novel sigma ligand, has antipsychotic effects and is free of side effects related to the extrapyramidal motoric system (EPMS). Here we report the results of an exploratory study aimed at determining the appropriate dose range and the safety of panamesine in patients with an acute episode of schizophrenia. The first trial with four patients revealed insufficient clinical efficacy of a protocol where the daily dosage was increased stepwise from 7.5 mg during week 1, up to 30 mg during weeks 3 and 4. In a second set of trials, 12 patients received 15 mg at the beginning, this being increased up to 60 mg/day within 3 days and then maintained at this level for 4 weeks. As assessed by a decrease in the Brief Psychiatric Rating Scale score by at least 50%, five patients were judged as responders, whereas six patients showed only a slight improvement, and one deteriorated. Moreover, intent-to-treat analysis showed significant improvement in psychometric variables. In all patients prolactin levels increased during treatment, probably due to an active metabolite with weak dopamine-2-receptor antagonistic effects. No major side effects occurred, and in particular, no EPMS symptoms were seen.
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Antipsicóticos/uso terapéutico , Oxazoles/uso terapéutico , Piperidinas/uso terapéutico , Receptores sigma/efectos de los fármacos , Esquizofrenia/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Escalas de Valoración Psiquiátrica Breve , Femenino , Humanos , Masculino , Prolactina/sangre , Sueño/efectos de los fármacosRESUMEN
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.
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Antipsicóticos/farmacología , Oxazoles/farmacología , Piperidinas/farmacología , Receptores sigma/agonistas , Esquizofrenia/inmunología , Sueño/efectos de los fármacos , Adyuvantes Inmunológicos/farmacología , Adolescente , Adulto , Recuento de Células Sanguíneas/efectos de los fármacos , Método Doble Ciego , Electroencefalografía/efectos de los fármacos , Femenino , Humanos , Locus Coeruleus/efectos de los fármacos , Masculino , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismo , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Rapid eye movement (REM) sleep deprivation leads to an induction of galanin gene expression in the rat brain, especially in the hypothalamus. Galanin affects neuroendocrine systems that are involved in sleep regulation, i.e. the growth hormone-releasing hormone-dependent system of the hypothalamus and the locus coeruleus. In the study reported here we investigated the effects of 4 x 50 microg galanin (n = 10) and of 4 x 150 microg galanin (n = 8) administered hourly between 22.00 and 01.00 h as intravenous boluses on the sleep EEG and nocturnal hormone secretion in healthy young men. Galanin administration significantly increased REM sleep in the third sleep cycle with no difference between the two doses. Spectral analysis revealed a significant increase in the EEG power in the delta and theta frequency range for the total night after the lower dose of galanin, but not after the higher dose. The secretion of growth hormone, cortisol and prolactin remained unchanged during sleep in both cases. Our data are consistent with the assumption of a functional resemblance between the effect of galanin and that of REM sleep deprivation, which is known to have antidepressive efficacy.
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Electroencefalografía/efectos de los fármacos , Galanina/administración & dosificación , Fases del Sueño/efectos de los fármacos , Sueño REM/efectos de los fármacos , Adulto , Análisis de Varianza , Hormona de Crecimiento Humana/sangre , Humanos , Hidrocortisona/sangre , Inyecciones Intravenosas , Masculino , Análisis Multivariante , Prolactina/sangre , Valores de Referencia , Privación de Sueño/fisiología , Fases del Sueño/fisiología , Sueño REM/fisiologíaRESUMEN
Leptin, the protein product of the obese (ob) gene, has been suggested to play a role in the regulation of food intake. As depressive episodes are frequently characterized by loss of appetite, reduced food intake and weight loss, altered leptin secretion might also be expected in patients with depression. Therefore, we examined nocturnal (10.00 p.m. to 7.00 a.m.) secretion of leptin, cortisol, ACTH and growth hormone (GH) in a group of 15 patients with depression and age- and sex-matched controls (age range 23-71 years). In addition, the effects of pulsatile administration of growth hormone-releasing hormone (GHRH), thought to be an endogenous antagonist of corticotropin-releasing hormone (CRH), which in turn is believed to play a critical role for the pathophysiology of depression, on nocturnal hormone secretion were assessed. Patients with depression showed a trend towards elevated nocturnal cortisol secretion (F = 3.8, p < 0.05). Nocturnal serum leptin was significantly higher in patients, despite a reported weight loss (F = 8, p < 0.05), but showed the same sexual dimorphism as in controls (F = 20.9, p < 0.01). No significant differences were seen between patients and controls with regard to plasma GH and ACTH. GHRH treatment increased GH secretion in both patients and controls, while the other hormones were not affected. Furthermore, serum leptin was correlated with body mass index (BMI) in controls, but not in patients with depression, supporting an altered regulation of leptin secretion in depressive illness. Finally, we provide some evidence that in young female patients the normal nocturnal leptin surge is blunted. As glucocorticoids can prevent the fasting-induced decline in serum leptin, we propose that hypercortisolism in depression might counteract the reduction in leptin secretion caused by decreased food intake and weight loss. Elevated serum leptin in depression might in turn further promote CRH release, as shown in animals and, hence, contribute to HPA system hyperactivity seen in depression.
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Ritmo Circadiano/fisiología , Depresión/sangre , Sistema Hipófiso-Suprarrenal/fisiopatología , Proteínas/análisis , Hormona Adrenocorticotrópica/sangre , Adulto , Anciano , Índice de Masa Corporal , Distribución de Chi-Cuadrado , Femenino , Hormona Liberadora de Hormona del Crecimiento/administración & dosificación , Hormona de Crecimiento Humana/sangre , Humanos , Hidrocortisona/sangre , Leptina , Masculino , Persona de Mediana Edad , Pruebas de Función Hipofisaria/métodos , Factores SexualesRESUMEN
Well documented changes of sleep electroencephalogram (EEG) in patients with depression include rapid eye movement (REM) sleep disinhibition, decreases of slow-wave-sleep (SWS) and increase in wakefulness. Twenty-seven inpatients with major depression were admitted subsequently to a clinical trial with the CRH(1)-receptor-antagonist R121919 administered in two different dose escalation panels. A random subgroup of 10 patients underwent three sleep-EEG recordings (baseline before treatment, at the end of the first week and at the end of the fourth week of active treatment). SWS time increased significantly compared with baseline after 1 week and after 4 weeks. The number of awakenings and REM density showed a trend toward a decrease during the same time period. Separate evaluation of these changes for both panels showed no significant effect at lower doses, whereas in the higher doses after R121919 REM density decreased and SWS increased significantly between baseline and week 4. Furthermore positive associations between HAMD scores and SWS at the end of active treatment were found. Although these data might indicate that R121919 has a normalizing influence on the sleep EEG, the design of the study does not allow to differentiate genuine drug effects from those of clinical improvement and habituation to the clinical setting.
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Trastorno Depresivo/complicaciones , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Trastornos del Sueño-Vigilia/etiología , Administración Oral , Adulto , Relación Dosis-Respuesta a Droga , Electroencefalografía/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
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.
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Electroencefalografía , Sueño/fisiología , Adulto , Análisis de Varianza , Humanos , MasculinoRESUMEN
Sub-chronic tryptophan depletion (SCTD) is proposed as an animal model for depression. Aims were to test the hypothesis and optimise the time of SCTD-induced depression-related behaviour and associated biochemical changes. Sprague Dawley rats were treated with a low tryptophan (TRP) containing diet for 0, 7 or 14 days. Peripheral and central neurochemical markers were measured. SCTD-induced depression-related behaviour was assessed by the forced swim test (FST). Model sensitivity to antidepressants was tested by concomitant treatment with paroxetine. SCTD-induced significant reductions in weight gain and measures of peripheral and central TRP. Corticosterone, aldosterone and kynurenine (K), increased whilst kynurenic acid (KA), an NMDA antagonist decreased. 5-HT(2) receptor binding Bmax was enhanced but was reversed by paroxetine. Corticosterone and aldosterone were significantly negatively-correlated to weight gain. SCTD increased floating time and reduced swimming time in the FST but were reversed by paroxetine. Aldosterone was increased at 7 and 14 days, whereas other changes maximised at 14 days. Aldosterone may be an early marker or causal link for depression development. Increased corticosterone and brain tissue 5-HT-receptor density may be correlates of depressive behaviour. Consequential increases in NMDA signalling through increased K/KA ratios suggest the model may be useful for testing novel antidepressants.