Slow wave sleep dreaming.

Fifty volunteers slept two nonconsecutive nights in a sleep laboratory under electropolygraphic control. They were awakened for one report per night. Awakenings were made, in counterbalanced order, from slow wave sleep (SWS--stage 3-4 and stage 4) and rapid eye movement (REM) sleep. Following dream reporting, subjects were asked to identify memory sources of their dream imagery. Two independent judges reliably rated mentation reports for temporal units and for several content and structural dimensions. The same judges also categorized memory sources as autobiographical episodes, abstract self-references, or semantic knowledge. We found that REM reports were significantly longer than SWS reports. Minor content SWS-REM differences were also detected. Moreover, semantic knowledge was more frequently mentioned as a dream source for REM than for SWS dream reports. These findings are interpreted as supporting the hypothesis that dreaming is a continuous process that is not unique to REM sleep. Different levels of engagement of the cognitive system are responsible for the few SWS-REM differences that have been detected.     

The GABA uptake inhibitor tiagabine promotes slow wave sleep in normal elderly subjects

Aging is associated with a dramatic decrease in slow wave sleep (SWS) and sleep consolidation. Previous studies revealed that various GABA(A) agonists and the GABA uptake inhibitor tiagabine augment slow frequency components in the EEG within non-REM sleep, and thus promote deep sleep in young individuals and/or rats. In the present double-blind, placebo-controlled study, we assessed the effect of a single oral dose of 5 mg tiagabine on nocturnal sleep in ten healthy elderly volunteers (6 females). During the placebo night the subjects displayed a low sleep efficiency, due to high amounts of intermittent wakefulness, and little SWS. Tiagabine significantly increased sleep efficiency, tendentially decreased wakefulness and prominently increased both SWS and low-frequency activity in the EEG within non-REM sleep. The present findings demonstrate that tiagabine increases sleep quality in aged subjects. Moreover, the effects of tiagabine closely match those evoked by the GABA(A) agonist gaboxadol in young subjects and indicate that such compounds may have prospects in the treatment of sleep disturbances, particularly of those commonly occurring in the elderly.     

Delta sleep EEG in depressed adolescent females and healthy controls

BACKGROUND: Quantitative EEG studies have identified a number of sleep abnormalities in adults with major depressive disorders (MDD), including a reduction in the amplitude of delta activity during NREM sleep. To date, these methodologies have not been used in early onset MDD. METHODS: Delta activity during NREM sleep was compared in eight symptomatic but unmedicated adolescent females with MDD and eight age- and gender-matched healthy controls. RESULTS: The depressed group showed significantly lower delta amplitude and power in the first NREM sleep period. By contrast, standard sleep architecture did not differentiate between groups. LIMITATIONS: Given the sample size, this study is best viewed as tentative. In addition, it has yet to be determined whether adolescent males with MDD also show delta sleep abnormalities. Further, failure to find between-group differences in REM latency or other macroarchitectural measures may be due to the small sample size. CONCLUSIONS: The findings of this study underscore the utility of quantitative sleep EEG techniques in early onset MDD. The results of the present study do, however, diverge from reports in adults with MDD, where delta abnormalities are more prevalent in men. Such findings suggest that the maturational time course of sleep EEG disturbances may differ for males and females with depression. Early emergence of delta abnormalities in depression may be of relevance to clinical course of illness.     

Cardiac rhythm in healthy elderly subjects

Summary To study the normal cardiac rhythm in elderly subjects we performed 24-h Holter monitoring on 94 subjects aged over 70 years. We had previously discarded those with cardiac disease by using history, physical examination, electrocardiography (ECG), chest X-radiography and Doppler echocardiography. The maximum, average and minimum heart rates were 113, 79 and 62, respectively, during the day, and 90, 64 and 53 during the night. Supraventricular and ventricular arrhythmias were frequent (91% and 89.4% respectively). Some 50% of the subjects had complex ventricular arrhythmias. Two subjects presented with sinus pauses of more than 2 s, and 4 had Wenckebach second-degree atrioventricular (AV) block. During a follow-up averaging 20.8 months, there were no deaths or symptoms of an arrhythmic origin.Abbreviations ECG electrocardiogram - AV atrioventricular - HBP hypertension - AT atrial tachycardia - FC functional class - VT ventricular tachycardia - bpm beats per minute - SVE supraventricular extrasystoles - AF atrial fibrillation - VE ventricular extrasystole - W-AVB Wenckebach atrioventricular block     

Diurnal preference, sleep habits, circadian sleep propensity and melatonin rhythm in healthy human subjects

We studied the in vitro effects of ethanol (25, 50 and 100 mM) on pyroglutamyl aminopeptidase activity (pGluAP), which has been reported as thyrotrophin-releasing-hormone-degrading activity. pGluAP was measured in presence or absence of calcium, under basal and K(+)-stimulated conditions, in synaptosomes and their incubation supernatant, using pyroglutamyl-beta-naphthylamide as substrate. In basal conditions, in synaptosomes, pGluAP was inhibited by ethanol in a calcium-independent way. In the supernatant, the response differed depending on the concentration of ethanol. Depolarization with K(+) modified pGluAP in synaptosomes and supernatant depending on the presence or not of calcium. In synaptosomes, in absence of calcium, the activity was inhibited at the highest concentrations of ethanol. In contrast, in the supernatant, under depolarizing conditions, ethanol increases pGluAP in absence of calcium. These changes may be in part responsible of the behavioural changes associated to alcohol intake.     

Diurnal preference, sleep habits, circadian sleep propensity and melatonin rhythm in healthy human subjects

After 24-h sleep deprivation, 33 healthy young subjects entered the 10/20 min ultra-short sleep–wake schedule for 26 h. Melatonin rhythm was hourly assessed simultaneously. Results indicated that morning preference was significantly correlated with habitual sleep onset (r=−0.41, P=0.04), habitual sleep offset (r=−0.52, P=0.002), melatonin peak time (r=−0.36, P=0.04), and sleep propensity onset time (r=−0.36, P=0.04). The intervals between habitual sleep mid-point and melatonin peak time and between habitual sleep mid-point and sleep propensity onset time were significantly longer in morning-preference subjects than in evening-preference subjects (P<0.05). These findings suggest that the variance of diurnal preference may be related to differences in phase relations between habitual sleep timing and the circadian pacemaker.     

Similar sleep EEG topography in middle-aged depressed patients and healthy controls

OBJECTIVES: One of the early hypotheses relating sleep disturbances in depression to a model of sleep regulation is the S-deficiency hypothesis. It is postulated that, in depressed patients, sleep propensity during wakefulness does not rise to the level attained by nondepressed subjects, resulting in altered sleep structure or changes in the electroencephalogram during sleep. We aimed to test this hypothesis by assessing topographic changes in the sleep electroencephalogram associated with depression. DESIGN: Cross-sectional clinical study. SETTING: Mental Health Clinical Research Center. PARTICIPANTS: Sixteen unmedicated depressed outpatients (mean age: 41.2 years) and 16 pair-matched healthy controls (mean age: 41.1 years). Interventions: None. MEASUREMENTS: Baseline sleep electroencephalogram recordings were obtained from a central referential electrode and from 3 bipolar derivations (frontocentral, centroparietal, parietooccipital) along the anteroposterior axis. RESULTS: Symptoms of depression at the time of sleep recordings were moderate (24-item Hamilton Rating Scale of Depression range: 16-31). No differences between patients and controls were found in sleep variables and all-night electroencephalogram spectra in non-rapid-eye-movement and rapid-eye-movement sleep. The ultradian modulation of slow-wave activity (power within 0.75-4.5 Hz), as well as the exponential decline of slow-wave activity, during sleep did not differ between the groups. The statistical analyses of electroencephalogram power gradients between adjacent derivations revealed no Group x Derivation interactions. An anterior dominance in non-rapid-eye-movement sleep power was present in the 0.75- to 2-Hz range, which diminished throughout the night. CONCLUSIONS: These findings in moderately depressed patients do not support the existence of an S-deficiency during sleep. Because the build up of sleep propensity during waking can be dissociated from its decline, future studies need to investigate the waking electroencephalogram spectra in depression.     

Short note: oral contraceptives and sleep in depressed and healthy women

STUDY OBJECTIVES: To evaluate the effects of oral contraceptives (OCs) on sleep EEG in healthy women and in those with major depressive disorders (MDD). DESIGN: This archival study selected participants who had sleep EEG measured over two consecutive nights, following a five-day regularized sleep-wake routine. Between-groups multivariate analysis of variance (MANOVA) contrasted group and OC main effects and interactions on sleep architecture. SETTING: N/A PARTICIPANTS: Sixty-eight women (ages 14-46 years) diagnosed with major depressive disorder (MDD), 13 of whom were on OCs and 55 were not. Patients were symptomatic and untreated at the time of study. Thirty-seven healthy control women (ages 12-46 years), nine of whom were on OCs and 28 were not. INTERVENTIONS: N/A Measurements and Results: OC main effects were found for %SW and for REM latency. Significant OC x Group interactions were found for sleep latency and %REM. Sleep latency was significantly shorter on OCs, but only in healthy women. Women on OCs showed a shorter REM latency, more total REM time, and less slow-wave sleep than women who were not on OCs. CONCLUSIONS: The effects of OCs were generally larger in healthy women than in those with MDD. Moreover, OC use was associated with more disturbed sleep in healthy women. These findings imply that OC use may compromise sleep EEG differences between healthy and depressed women and may be more difficult to differentiate between depressed patients and healthy controls when sleep studies include women on OCs. These findings may also have implications for evaluating gender differences in sleep architecture.     

Slow wave sleep enhancement with gaboxadol reduces daytime sleepiness during sleep restriction

STUDY OBJECTIVES: To evaluate the impact of enhanced slow wave sleep (SWS) on behavioral, psychological, and physiological changes resulting from sleep restriction. DESIGN: A double-blind, parallel group, placebo-controlled design was used to compare gaboxadol (GBX) 15 mg, a SWS-enhancing drug, to placebo during 4 nights of sleep restriction (5 h/night). Behavioral, psychological, and physiological measures of the impact of sleep restriction were assessed in both groups at baseline, during sleep restriction and following recovery sleep. SETTING: Sleep research laboratory. PARTICIPANTS: Forty-one healthy adults; 9 males and 12 females (mean age: 32.0 +/- 9.9 y) in the placebo group and 10 males and 10 females (mean age: 31.9 +/- 10.2 y) in the GBX group. INTERVENTIONS: Both experimental groups underwent 4 nights of sleep restriction. Each group received either GBX 15 mg or placebo on all sleep restriction nights, and both groups received placebo on baseline and recovery nights. MEASUREMENTS AND RESULTS: Polysomnography documented a SWS-enhancing effect of GBX with no group difference in total sleep time during sleep restriction. The placebo group displayed the predicted deficits due to sleep restriction on the multiple sleep latency test (MSLT) and on introspective measures of sleepiness and fatigue. Compared to placebo, the GBX group showed significantly less physiological sleepiness on the MSLT and lower levels of introspective sleepiness and fatigue during sleep restriction. There were no differences between groups on the psychomotor vigilance task (PVT) and a cognitive test battery, but these measures were minimally affected by sleep restriction in this study. The correlation between change from baseline in MSLT on Day 6 and change from baseline in SWS on Night 6 was significant in the GBX group and in both group combined. CONCLUSIONS: The results of this study are consistent with the hypothesis that enhanced SWS, in this study produced by GBX, reduces physiological sleep tendency and introspective sleepiness and fatigue which typically result from sleep restriction.     

Caffeine consumption, sleep, and affect in the natural environments of depressed youth and healthy controls

OBJECTIVE: Sleep problems are a cardinal symptom of depression in children and adolescents and caffeine use is a prevalent and problematic issue in youth; yet little is known about caffeine use and its effects on sleep in youth with depression. We examined caffeine use and its relation to sleep and affect in youth's natural environments. METHODS: Thirty youth with major depressive disorder (MDD) and 23 control youth reported on caffeine use, sleep, and affect in their natural environment using ecological momentary assessment at baseline and over 8 weeks, while MDD youth received treatment. RESULTS: Youth with MDD reported more caffeine use and sleep problems relative to healthy youth. Youth with MDD reported more anxiety on days they consumed caffeine. Caffeine use among youth with MDD decreased across treatment, but sleep complaints remained elevated. CONCLUSIONS: Findings suggest that both sleep quality and caffeine use are altered in pediatric depression; that caffeine use, but not sleep problems, improves with treatment; and that caffeine may exacerbate daily anxiety among youth with depression.     

Dietary intake and clinical, anthropometric and biochemical indices of malnutrition in elderly demented patients and non-demented subjects

Anthropometric and biochemical indices of nutritional status and weighed dietary intake have been studied in hospitalized patients with senile dementia, demented patients living in the community and age-matched control subjects who were not cognitively impaired. Demented patients were lighter than control subjects, and had a lower body mass index, skinfold thickness, mid-arm circumference and arm muscle bulk. The hospitalized patients were more seriously affected than those living in the community, and body weight was significantly negatively correlated with duration of hospitalization. Over a 6-month period the hospitalized patients showed a further weight loss, while those living in the community did not. Both groups of demented patients had higher intakes of energy, protein, vitamins and minerals than the control subjects. The diet of the hospitalized patients was slightly, but not significantly, superior to that of the patients living in the community. Biochemical evidence of specific vitamin inadequacy was equally prevalent in all three groups of subjects, and there were no significant correlations between the degree of cognitive impairment or behavioural disorder and any of the indices of nutritional state. Clinical signs suggestive of malnutrition were not correlated with either biochemical evidence of deficiency or cognitive impairment and behavioural disturbance.     

Gender differences in the circadian temperature rhythms of healthy elderly subjects: relationships to sleep quality

Body core temperature and subjective sleep quality were measured in 22 healthy elderly men and women while they lived at home and continued their normal daily activities. The acrophase of body temperature was phase-advanced by an average of 1.25 h in the older women compared to the age-matched men. Habitual bedtimes did not differ between men and women, but usual wakeup time and average sleep duration did: women awakened earlier and slept for shorter durations. Women were also less satisfied with their sleep than were the men. For the group, the acrophase of body temperature was significantly positively correlated with habitual bedtime and wakeup time. These data support the notion that age-related changes in the circadian timing system are, in large part, gender-dependent. The findings are also consistent with the hypothesis that alterations in sleep timing and quality that typically accompany aging are closely tied to age-related changes in circadian physiology.     

Electroencephalographic sleep and natural killer activity in depressed patients and control subjects.

Insomnia is associated with a reduction of natural killer (NK) activity in depression independent of the severity of other depressive symptoms. This study extends these findings by exploring the relationship between objective electroencephalographic (EEG) assessment of sleep and values of NK activity in depressed patients (n = 23) and in control subjects (n = 17). The sleep EEG parameters total sleep time, sleep efficiency, and duration of nonREM sleep were each positively correlated with NK activity in the depressed patients and in the control subjects, demonstrating similar relationships between the amount of sleep and NK activity in the separate groups. These observations support the hypothesis that sleep measures are associated with NK cytotoxicity, independent of the effects of severity of depressive symptoms or the presence of a mood disorder.     

Effects of intravenous catheter on sleep in healthy men and in depressed patients

The effects of intravenous catheter and nocturnal blood samplings at frequent intervals on sleep electroencephalogram (EEG) variables were investigated in 8 male healthy controls and 12 depressed patients, who were studied in the same experimental conditions. After one night of habituation, sleep was recorded during 4 consecutive nights in the sleep laboratory. A catheter was inserted around noon the day before the fourth night, and blood was sampled every 15 min for 25 h. The night-to-night comparison of sleep EEG variables did not show significant sleep continuity modifications in the control subjects, other than a weak trend toward an increase in nocturnal awakenings during the night with the catheter. A lengthening of sleep onset latency during the fourth night was found in the depressed patients. No significant changes were detected in percentage of rapid eye movement (REM) sleep in the two groups. However, a gradual increase in Stage 3 was observed across the 4 nights in the control subjects. These results indicate that intravenous blood sampling via a catheter can be performed without inducing significant disruption of sleep length and structure.     

Heterogeneity of immune responsiveness in healthy elderly subjects

We studied a group of healthy elderly subjects (satisfying the SENIEUR Protocol admission criteria), chosen as a model of age-associated immune deficiency on the basis of their reduced skin reactivity to recall antigens. Results show that aged subjects, taken as a whole, display impaired T-cell functions: reduced blastogenetic responses to mitogens, IL-2 production, responsiveness to exogenous IL-2, and percentage of Tac positive blasts. However, the age-associated immune defect shows a wide range of impairment, even in a relatively homogeneous group of anergic/hypoergic subjects. In fact, a considerable proportion of our elderly subjects displays responses comparable with those of adult controls. These observations suggest that (a) immune deficiency is not a characteristic of aging per se; (b) cutaneous delayed hypersensitivity is not a criterion sensitive enough to identify people with age-associated immune deficit; and (c) more than one test is required to evaluate T-cell impairment in aging.     

Topographic distribution of sleep spindles in young healthy subjects

The application of an automatic sleep spindle detection procedure allowed the documentation of the topographic distribution of spindle characteristics, such as number, amplitude, frequency and duration, as a function of sleep depth and of recording time. Multichannel all-night EEG recordings were performed in 10 normal healthy subjects aged 20–35 years. Although the interindividual variability in the number of sleep spindles was very high (2.7±2.1 spindles per minute stage 2 sleep), all but two subjects showed maximal spindle activity in centro-parietal midline leads. Moreover, this topography was seen in all sleep stages and changed only slightly – to a more central distribution – towards the end of the night. On the other hand, slow (11.5–14 Hz) and fast (14–16 Hz) spindles showed a completely different topography, with slow spindles distributed anteriorly and fast spindles centro-parietally. The number of sleep spindles per min was significant depending on sleep stages, with the expected highest occurrence in stage 2, and on recording time, with a decrease in spindle density from the beginning towards the end of the night. However, spindle amplitude, frequency and individual duration was not influenced by sleep depth or time of the night.     

The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects

The aim of this study was to compare the effects of total sleep deprivation (TSD), rapid eye movement (REM) sleep and slow wave sleep (SWS) interruption and sleep recovery on mechanical and thermal pain sensitivity in healthy adults. Nine healthy male volunteers (age 26--43 years) were randomly assigned in this double blind and crossover study to undergo either REM sleep or SWS interruption. Periods of 6 consecutive laboratory nights separated by at least 2 weeks were designed as follows: N1 Adaptation night; N2 Baseline night; N3 Total sleep deprivation (40 h); N4 and N5 SWS or REM sleep interruption; N6 Recovery. Sleep was recorded and scored using standard methods. Tolerance thresholds to mechanical and thermal pain were assessed using an electronic pressure dolorimeter and a thermode operating on a Peltier principle. Relative to baseline levels, TSD decreased significantly mechanical pain thresholds (-8%). Both REM sleep and SWS interruption tended to decrease mechanical pain thresholds. Recovery sleep, after SWS interruption produced a significant increase in mechanical pain thresholds (+ 15%). Recovery sleep after REM sleep interruption did not significantly increase mechanical pain thresholds. No significant differences in thermal pain thresholds were detected between and within periods. In conclusion this experimental study in healthy adult volunteers has demonstrated an hyperalgesic effect related to 40 h TSD and an analgesic effect related to SWS recovery. The analgesic effect of SWS recovery is apparently greater than the analgesia induced by level I (World Health Organization) analgesic compounds in mechanical pain experiments in healthy volunteers.     

Slow wave sleep elevations after body heating: proximity to sleep and effects of aspirin

On three different occasions, six healthy young adult subjects ahd their body temperatures raised by an average of 2.0 degrees C for 30 min while sitting in baths of warm water. This was done once at 1700 h and on two occasions at 2100 h, once after the subjects had taken aspirin and once after a placebo. Nighttime sleep was recorded after each experimental condition and for baseline nights following nil heating. Records were scored both visually and by an automated sleep stager. Electroencephalographic (EEG) power was computed over the night. Results from the automated scoring were very similar to those of the visual method. While the early bath caused no changes in sleep, the late bath + placebo resulted in significant rises in stage 4 sleep and slow wave sleep (SWS) and significant falls in sleep onset and in REM sleep. Aspirin mostly counteracted these effects and, in particular, left stage 4 sleep and SWS at baseline levels. EEG power was significantly increased only after the late bath plus placebo, supporting the SWS outcome. These findings were assessed in light of other comparable results from our laboratory. It seems that as the time of the day of heating recedes from nighttime sleep, a larger "dose" of heating is required to produce the same effect.     

Exposure to light in healthy elderly subjects and Alzheimer's patients

Exposure to light was recorded from 10 healthy elderly adults and 13 age-matched subjects with senile dementia of the Alzheimer's type (SDAT). Data were recorded in the home, for an average of 5 days, while subjects continued their normal daily activities. Subjects were exposed to remarkably small intervals of illumination exceeding 2000 lux. Subjects with SDAT were exposed to bright light significantly less than healthy controls (0.5 vs. 1.0 hr). Whether or not they had SDAT, males were exposed to illumination exceeding 2000 lux significantly more than were females. Healthy elderly received about two-thirds the duration of bright light received by healthy younger subjects. These findings suggest an association between decreased exposure to bright light and the declines in sleep quality which typically accompany normal and pathological aging.