Interrelations between sleep and the somatotropic axis

In the human as in other mammals, growth hormone (GH) is secreted as a series of pulses. In normal young adults, a major secretory episode occurs shortly after sleep onset, in temporal association with the first period of slow-wave (SW) sleep. In men, approximately 70% of the daily GH output occurs during early sleep throughout adulthood. In women, the contribution of sleep-dependent GH release to the daily output is lower and more variable. Studies involving shifts of the sleep-wake cycle have consistently shown that sleep-wake homeostasis is the primary determinant of the temporal organization of human GH release. Effects of circadian rhythmicity may occasionally be detected. During nocturnal sleep, the sleep-onset GH pulse is caused by a surge of hypothalamic GHRH release which coincides with a circadian-dependent period of relative somatostatin disinhibition. Extensive evidence indicates the existence of a consistent relationship between SW sleep and increased GH secretion and, conversely, between awakenings and decreased GH release. There is a linear relationship between amounts of SW sleep--whether measured by visual scoring or by delta activity--and amounts of concomitant GH secretion, although dissociations may occur, most likely because of variable levels of somatostatin inhibition. Pharmacological stimulation of SW sleep results in increased GH release, and compounds which increase SW sleep may therefore represent a novel class of GH secretagogues. During aging, SW sleep and GH secretion decrease with the same chronology, raising the possibility that the peripheral effects of the hyposomatotropism of the elderly may partially reflect age-related alterations in sleep-wake homeostasis. While the association between sleep and GH release has been well documented, there is also evidence indicating that components of the somatotropic axis are involved in regulating sleep. The studies are most consistent in indicating a role for GHRH in promoting NREM and/or SW sleep via central, rather than peripheral, mechanisms. A role for GH in sleep regulation is less well-documented but seems to involve REM, rather than NREM, sleep. It has been proposed that the stimulation of GH release and the promotion of NREM sleep by GHRH are two separate processes which involve GHRH neurons located in two distinct areas of the hypothalamus. Somatostatinergic control of GH release appears to be weaker during sleep than during wake, suggesting that somatostatinergic tone is lower in the hypothalamic area(s) involved in sleep regulation and sleep-related GH release than in the area controlling daytime GH secretion. While the concept of a dual control of daytime and sleep-related GH secretion remains to be directly demonstrated, it allows for the reconciliation of a number of experimental observations.     

The roles of time of day and sleep quality in modulating glucose regulation: clinical implications

Consistent variations in glucose regulation across the 24-hour cycle are present in normal subjects. These diurnal variations are altered in various states of impaired glucose tolerance (aging, obesity, diabetes). Changes in insulin secretion, clearance and/or action across the day have been demonstrated. Studies in subjects receiving continuous intravenous glucose infusion have shown that major alterations of glucose tolerance occur during sleep and that sleep quality markedly influences glucose utilization. Diurnal variations in glucose tolerance result from the alternation of wake and sleep states as well as from intrinsic effects of circadian rhythmicity. The important roles of physiological variations in levels of counterregulatory hormones which are markedly dependent on sleep (i.e. growth hormone) or circadian rhythmicity (i.e. cortisol) have only begun to be appreciated. The modulatory effects of sleep and circadian rhythmicity on glucose regulation may have important clinical implications for the diagnosis and treatment of abnormalities of carbohydrate metabolism.     

Ultradian rhythms in hydromineral hormones

The maintenance of hydromineral homeostasis depends on the coordinated action of arginine vasopressin (AVP), atrial natriuretic peptide (ANP), the renin-angiotensin-aldosterone system and other recently identified endocrine or paracrine hormones. Several reports have pointed out the changes in urinary excretion and osmolality during the sleep-wake cycle and the rapid eye movement (REM)-non(N)REM sleep cycles. No such changes occur for ANP levels which have a flat profile over 24 h. The pulsatile fluctuations of AVP are described as random. The ultradian rhythm of plasma renin activity (PRA) depends on the regularity of the REM-NREM sleep cycles and the nocturnal curves reflect all disturbances in the internal sleep structure. A study with a shift in the normal sleep time clearly demonstrated that both PRA and aldosterone oscillations are sleep-stage dependent. These hormones could account for the ultradian variations in renal function. The nocturnal oscillations in sympathovagal balance may play an additional role. It is suggested that a central generator synchronizes endocrine, renal, autonomic and sleep processes.     

Non-24-hour sleep-wake syndrome in a sighted man: circadian rhythm studies and efficacy of melatonin treatment

The case of a 41-year-old sighted man with non-24-hour sleep-wake syndrome is presented. A 7-week baseline assessment confirmed that the patient expressed endogenous melatonin and sleep-wake rhythms with a period of 25.1 hours. We sought to investigate the underlying pathology and to entrain the patient to a normal sleep-wake schedule. No deficiency in melatonin synthesis was found. Furthermore, normal coupling between the melatonin and sleep propensity rhythms was documented using an "ultrashort" sleep-wake protocol. Environmental light exposure was monitored for 41 days, and the circadian timing was calculated. Sensitivity to photic input was determined with light-induced melatonin-suppression tests. Three intensities (500, 1,000, and 2,500 lux) were examined during three separate trials. The 2,500-lux trial resulted in 78% suppression, but the lesser intensity exposures were without substantial effect. Thus, the patient appeared to be subsensitive to bright light. A 4-week trial of daily melatonin administration (0.5 mg at 2100 hours) stabilized the endogenous melatonin and sleep rhythms to a period of 24.1 hours, albeit at a somewhat delayed phase. A 14-month follow-up interview revealed that the patient continued to take melatonin daily, and his sleep-wake schedule was stable to a near 24-hour schedule.     

Effects of ageing on modulation of hormonal secretions by sleep and circadian rhythmicity

Circadian rhythmicity persists in healthy elderly subjects but a number of 24 hour rhythms are dampened and/or advanced in old age. The tendency for earlier sleep onset, earlier morning awakening and a more fragmented and more shallow sleep period is representative of these alterations. Other overt rhythms which have been shown to be of lower amplitude and/or phase-advanced are those of body temperature and of the peripheral levels of hormones such as cortisol, melatonin, TSH, testosterone, prolactin and GH. Mean hormonal levels are generally decreased, but overall cortisol secretion is increased with ageing. These modifications are likely to be partially due to alterations of the circadian central nervous system processes controlling circadian rhythmicity and sleep.     

Ocular bubble formation as a method of assessing decompression stress

Human well-being depends on the entrainment of endogenous circadian rhythms of biological functions and the sleep-wake rhythm. Although the incidence of otherwise healthy subjects with chronically altered sleep-wake rhythms is rather low, the investigation of these patients provides new sights into circadian entrainment mechanisms. We therefore examined the circadian rhythm of circulating melatonin and the sleep-wake rhythm in five patients with chronic sleep-wake rhythm disorders and ten age-matched healthy controls. All patients showed altered circadian melatonin rhythm parameters in relation to their sleep-wake cycle compared to age-matched controls. These alterations were random, i.e., independent of the type, the duration, and the age of onset of the disorder. The melatonin onset to sleep onset interval varied between the patients and the melatonin acrophase to sleep offset interval was prolonged in four patients. These findings indicate individual phase relations between the circadian melatonin rhythm and the sleep-wake cycle in patients with chronic sleep-wake rhythm disorders. Since the prolonged melatonin acrophase to sleep offset interval was the most consistent finding independent of aetiological origins, this abnormality may be one possible maintaining factor in chronic sleep-wake rhythm disorders due to reduced phase-resetting properties of the circadian pacemaker. Furthermore, rather low circadian melatonin amplitudes and a subsensitivity to daylight may maintain the disorder in at least some patients.     

Circadian rhythms during gradually delaying and advancing sleep and light schedules

The circadian rhythms of the night shift worker show very little phase shift in response to the daytime sleep and night work schedule. One strategy for producing circadian adaptation may be to use appropriately timed exposure to high-intensity light. We attempted to shift the circadian temperature rhythms of seven normal subjects while they followed a sleep schedule that gradually delayed (2 h per day) until sleep occurred during the daytime, as is customary for workers during the night shift. After 5 days, the sleep schedule was gradually advanced back to baseline. High illuminance light (2 h per day) and the attenuation or avoidance of sunlight were timed to facilitate temperature rhythm phase shifts. In general, the temperature rhythm did not shift along with the sleep-wake schedule, but appeared either to free run or remain entrained to the natural 24-h zeitgebers. This study showed how difficult it can be to shift human circadian rhythms in the field, when subjects are exposed to competing 24-hr zeitgebers.     

Burkholderia pseudomallei: the unbeatable foe?

The sleep-wake cycle in non-24-hour sleep-wake syndrome is longer than 24 hours. Patients go to bed a little bit later each day and then can not fall asleep and wake up at the usual time. The same sleep patterns and free running rhythms in healthy subjects have been seen in temporal isolation. The mechanism of this syndrome has not been clarified, but several factors have been proposed as follows: 1) the weakness of Zeitgeber 2) decrease of sensitivity to Zeitgeber 3) the period of the circadian system is much longer than 24 hours. Vitamin B12 and melatonin were reported to be effective in treating this syndrome.     

Perineurioma of the finger: case report of a rare peripheral nerve sheath neoplasm of pure perineurial cell lineage

Pituitary hormone secretion is changed by sleep-awake rhythm, which also regulates by the hypothalamo-pituitary axis. The endocrine rhythm is also affected by such factors as aging and environment conditions. Nocturnal secretion of growth hormone is known to be induced by slow-wave sleep. Plasma prolactin levels seem to increase during REM sleep. Serum thyroid stimulating hormone levels increase during the night. Plasma adrenocorticotropin and cortisol levels increase in the early morning and decreased in the night, which are not related to the sleep stage. The sleep-related hormone secretion is not shown in the patients with disordered hypothalamo-pituitary axis. The evaluation of sleep-related changes in pituitary hormone is important to assess the hypothalamo-pituitary function.     

Systematic 24-hr behavioral observations of sleep and wakefulness in a skilled-care nursing facility.

Sleep patterns of aged, infirm, demented, chronically institutionalized residents of a skilled-care nursing facility were studied. The purpose of this naturalistic study was to describe sleep and wakefulness (S/W) within the limits afforded by brief behavioral observations and to examine homeostasis and diurnal rhythmicity of S/W as a function of psychoactive drug intake. Observers noted S/W every 15 min, 24 hr a day for 10 days in 24 Ss. Results indicated substantial individual variation in daytime hours. Daily and weekly variation within Ss was minimal. Sleep was least likely near sunset. Ss on psychoactive drugs showed dampened diurnal variation in S/W rhythms. In Ss not on such drugs, there was a suggestion of homeostasis of S/W between sleep during the morning and evening hours. Results are discussed methodologically (viability of approach), theoretically (age-related change in sleep), and practically (potential treatments). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disturbances of sleep and cognitive functioning in patients with dementia

The relationship of sleep, circadian rhythms, and cognitive impairment in dementia patients is briefly reviewed. All-night sleep EEG data were collected in relatively young and relatively unimpaired patients with presumptive Alzheimer's disease and eight age-matched controls. Delta sleep time and Delta sleep % (Stages 3 and 4)--but not REM sleep measures--were significantly reduced in the patients. Implications of these findings are discussed.     

The role of melatonin in the human fetus (review)

Melatonin, an indole amine, primarily derived from the pineal gland is secreted during the hours of darkness. Melatonin acts as a hormonal transduction of photoperiod influencing the timing of seasonal and daily (circadian) physiological rhythms. Maternal melatonin crosses the placenta and enters the fetal circulation providing photoperiodic information to the fetus influencing the subsequent circadian and seasonal rhythms of the offspring. The function of melatonin in humans is more obscure. However, melatonin has attained prominence as a treatment for disturbed circadian rhythms and sleep patterns which occur as a result of transmeridian travel, shift work or blindness. The biological clock, the hypothalamic suprachiasmatic nuclei (SCN), possesses melatonin receptors, in both the adult and fetal human. This concurs with the reported influence of melatonin on human circadian rhythmicity and indicates that this influence may begin in utero. Melatonin receptors are widespread in the human fetus and occur in both central and peripheral tissue from early in fetal development. Thus, the influence of melatonin on the developing human fetus may not be limited to entraining circadian rhythmicity. Considering the transplacental availability of melatonin to the fetus the ingestion of melatonin by pregnant women may be inadvisable.     

Use of dynamic two-dimensional transesophageal echocardiography for renal cell carcinoma with cavoatrial tumor thrombus

Previous investigations involving continuous blood pressure (BP) monitoring have shown an important alteration of the 24-hour BP profile in patients with obstructive sleep apnea syndrome (OSAS). We investigated the impact of REM sleep on the 24-hour BP cycle in 16 severe OSAS male patients (mean respiratory disturbance index = 66 +/- 16 events/hour of sleep), with hypertension (mean BP 162 +/- 21/105 +/- 11 mmHg World Health Organization (WHO) protocol). Two successive nights of polysomnography were performed, and arterial BP was monitored continuously during the second 24-hour period after brachial artery cannulation. During the daytime, subjects were kept awake and supine. At 3 p.m. BP was continuously monitored during quiet supine wakefulness for 20 minutes. Systolic, diastolic and mean BP and heart rate (HR) were analyzed and tabulated in mean values of 5 minute segments. Sleep/wake information were correlated with cardiovascular variables. Each uninterrupted REM sleep period was identified and comparison between the period of quiet supine wakefulness and REM sleep HR and BP values was performed. 8 OSAS patients presented a normal drop of the mean arterial BP during the nocturnal REM sleep periods compared to quiet supine wakefulness (mean value = -10.8 +/- 7.3 mmHg) ("dippers") while the other 8 subjects ("REM sleep non dippers"), revealed an elevated mean arterial BP during REM sleep (mean value = 18.9 +/- 10.9 mm Hg). The absence of the normal circadian BP dip seen during the nocturnal sleep period is considered as an indication of vascular risk. The REM sleep non dipping may play a role in this risk.     

Sleep in relation to age, sex, and chronotype in Japanese workers

The Morningness-Eveningness Questionnaire and Life Habits Inventory were administered to 622 Japanese workers matched for sex and age. We investigated the distributions of the scores on the Morningness-Eveningness Questionnaire and sleep-wake habits by age and sex. Subjects were classified into five age groups and three chronotypes. The distributions and mean scores on the questionnaire advanced slightly toward the Morning type from the young to the aged group. The habitual bedtimes and waking times were significantly earlier in all the chronotypes from the young to the aged group, and the preferred bedtimes and waking times were also clearly earlier from the young to the aged group. The length of sleep was shorter for the Evening than the Morning types, especially in the group below 24 yr. The differences in habitual and preferred sleep length were greater than 1 hour for all age groups, especially the two groups under 34 yr. The number of awakenings during night sleep increased from the young to the aged group for all chronotypes. The older Evening type tended more toward frequent napping and longer naptime. The variabilities of bedtime and sleep length were larger for the young and Evening type than for the old group and Morning types. Further, the mood upon waking and satisfaction with sleep length were better in the aged Evening type than the young Morning type. The women under 44 yr. woke up earlier than the men of the same age, and the women of the 35-54 yr. groups had a shorter length of sleep than others. These may be related to childcare and housework. These results indicated that the phase of circadian rhythms had moved forward from the young to the aged group, and the individual's rhythm, of those that were aged Morning types, showed better agreement with sleep-wake rhythms than did others.     

Polysomnographie, chronobiologie et approche cognitive dans le traitement de la dépression majeure.

Apart from pharmacotherapy and biological conceptualisations, the cognitive theory and its therapeutic approach are likely the most used in the conceptualization and the treatment of major depression. The cognitive model attempts to explain how certain factors activate a dysfunctional cognitive structure. As such, the cognitive therapy focuses on the modification of negative and depressive cognitive distortions. Despite a success rate of approximately 66%, a significant proportion of patients (30%) suffer a relapse within one year of treatment. This suggests that the cognitive approach is not sufficient to explain the development, maintenance, remission and relapse of a major depressive episode. It is proposed here that sleep and chronobiological factors should be taken into consideration in order to improve the understanding of major depression and to maximize the chances of complete remission in those who suffer from this disorder. Indeed, both research and clinical reports have revealed that major depression is accompanied by sleep disruptions. More specifically, three types of problems have been identified: (1) Sleep discontinuity (reduced total sleep time, increased sleep latency, increased awakenings, reduced sleep efficiency); (2) decreases in slow wave sleep (SWS); (3) changes in rapid eye movement (REM) sleep characteristics (decreased REM latency, increased REM density, increase in the length of the first REM period and in the quantity of REM sleep). Of particular interest is the observation that, when the depressive symptoms disappear, sleep improves. Recent research, however reveals that certain sleep abnormalities, namely short REM latency and reduced SWS, are more robust or trait-like and are indicators of an increased risk of relapse. Furthermore, other studies suggest that the presence of these sleep abnormalities may facilitate the onset of depression. Models of sleep-wake regulation which have attempted to explain the sleep characteristics of depression are reviewed. These point to underlying chronobiological factors such as phase advances of circadian rhythms and suggest that such factors are responsible for the manifestation of the sleep disturbances observed in major depression. Fortunately, techniques that improve sleep quality and resynchronize the biological rhythms are available. Sleep hygiene maximizes sleep habits that facilitate normal sleep, particularly sleep initiation, sleep continuity and length of sleep. On the chronobiological side, bright light exposure and sleep schedule manipulations can resynchronize sleep periods with the appropriate circadian phase. It is thus proposed that sleep recordings, namely polysomnography, which have recently become more readily available (particularly with ambulatory devices), be used to select adequate treatment, and to support decisions regarding treatment duration. Similarly, sleep hygiene and chronobiological treatments should be integrated in the treatment of major depression. This article concludes by proposing a hierarchical model of interventions that combine polysomnography and chronobiological techniques with the classic cognitive approach to major depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sleep electroencephalographic abnormalities in adolescent depressives: effects of scopolamine

In contrast to sleep studies of adult depressives that have consistently demonstrated abnormalities of sleep continuity, slow-wave sleep, and REM sleep, existing studies of depressed children and adolescents have been conflicting. Furthermore, only one study has explored the cholinergic regulation of sleep in early-onset depressives. In the present study, the electroencephalographic sleep of 20 adolescent outpatients with major depressive episodes and 13 normal control adolescents was obtained on two separate 2-night sessions, 1 night incorporating challenge with scopolamine. Depressed adolescents showed increased baseline phasic REM sleep measures, increased arousals, a trend toward reduced slow-wave sleep, and a greater difference in the change of first REM period density on the scopolamine night versus placebo night compared to controls. These findings support the continuity of some sleep abnormalities of depression into adolescence, and suggest that adolescent depression may be associated with alterations of cholinergic neurotransmission in some patients.     

The influence of a heavy thermal load on REM sleep in the rat

This study was carried out in order to further test the hypothesis that the occurrence of REM sleep in the rat in the form of episodes separated by long intervals (single REM sleep episodes) and by short intervals (sequential REM sleep episodes) is differently influenced by changes in both sleep and ambient related processes. Rats were studied during the exposure to Ta -10 degrees C for 24 or 48 h and during a 12 h recovery period at laboratory Ta (23 degrees C) following either the first or the second 24 h of cold exposure. The exposure to such a low Ta induced an almost complete abolition of REM sleep which was followed, during recovery, by a marked REM sleep rebound. However, in spite of the larger REM sleep deprivation, the REM sleep rebound was weaker following the 48 h-exposure than that following the exposure for 24 h. The increase in the amount of REM sleep during the recovery period was due to an increase in the amount of that occurring in the form of sequential episodes, whilst that in the form of single episodes did not change with respect to control levels. However, the occurrence of REM sleep in the form of sequential episodes was partially impaired during the REM sleep rebound observed in the recovery period following the 48 h-exposure. These results would suggest that the homeostatic regulation of physiological variables may conflict with that of REM sleep occurrence and that the degree of such a contrast is indicated, at low Ta, by the amount of REM sleep in the form of single episodes and, during the following recovery, by the amount of REM sleep in the form of sequential episodes.     

Polysomnography and other methods for the assessment of sleep disorders

Polysomnography is an essential tool in the assessment of sleep disorders. However, PSG alone not always sufficient to evaluate various sleep disorders patients. For instance, in patients with suspected inadequate sleep hygiene, sleep logs or questionnaires on sleep habits may, be helpful in making the diagnosis. Patients who complain of excessive daytime sleepiness as a result of insomnia should be evaluated with the Epworth sleepiness scale and/or polysomnographic nap studies such as the multiple sleep latency test. In patients with suspected circadian rhythm sleep disorder, continuous temperature monitoring together with sleep log and actigraphy may establish the phase relationship between sleep-wake rhythms and other biological rhythms. Because polysomnographic measurements are cumbersome and expensive, it is necessary to select the suitable methods for the assessment of sleep disorders by the careful examination of the patients' complain.     

Circadian rhythms

1997 marks the 25th anniversary of the discovery of the master circadian pacemaker in mammals in the hypothalamic suprachiasmatic nucleus. Remarkable progress has been made over the last 25 years in elucidating the physiological mechanisms involved in the entrainment, generation and expression of circadian rhythms at the cellular and systems levels. The recent discovery and cloning of the first mammalian clock gene is expected to lead to rapid advances in the understanding of the genetic and molecular mechanisms underlying circadian rhythmicity in mammals. Indeed, the impressive and extensive database on circadian rhythms in mammals obtained over the past 25 years provides a foundation for making rapid progress in utilizing future genetic and molecular findings for discovering the fundamental mechanisms controlling 24-hour temporal organization.