Homovanillic acid and 5-hydroxyindoleacetic acid in lumbar cerebrospinal fluid after total and REM sleep deprivation in humans.

Lumbar CSF HVA and 5-HIAA levels were assayed in 3 groups each of 10 subjects, which were respectively deprived of sleep for 30 h, deprived of REM sleep and disturbed with several awakenings during SW sleep for two consecutive nights. HVA levels after total sleep (39 +/- 20 ng/ml) or REM (35 +/- 11 ng/ml) deprivation as well as after SW sleep awakenings (32 +/- 26 ng/ml) were not different from controls (42 +/- 14 ng/ml). 5-HIAA levels after REM deprivation (32 +/- 15 ng/ml) appeared increased when compared with controls (21 +/- 7 ng/ml), total sleep-deprived subjects (21 +/- 10 ng/ml) or subjects with SW sleep awakenings (27 +/- 13 ng/ml). Possible increase in 5-HT turnover after REM deprivation and possible 5-HT role in REM sleep regulation in humans are discussed.     

Effects of different sleep deprivation protocols on sleep perception in healthy volunteers

Objectives

To investigate whether different protocols of sleep deprivation modify sleep perception.

Methods

The effects of total sleep deprivation (TD) and selective rapid eye movement (REM) sleep deprivation (RD) on sleep perception were analyzed in normal volunteers. Thirty-one healthy males with normal sleep were randomized to one of three conditions: (i) normal uninterrupted sleep; (ii) four nights of RD; or (iii) two nights of TD. Morning perception of total sleep time was evaluated for each condition. Sleep perception was estimated using total sleep time (in hours) as perceived by the volunteer divided by the total sleep time (in hours) measured by polysomnography (PSG). The final value of this calculation was defined as the perception index (PI).

Results

There were no significant differences among the three groups of volunteers in the total sleep time measured by PSG or in the perception of total sleep time at baseline condition. Volunteers submitted to RD exhibited lower sleep PI scores as compared with controls during the sleep deprivation period (P < 0.05). Both RD and TD groups showed PI similar to controls during the recovery period.

Conclusion

Selective REM sleep deprivation reduced the ability of healthy young volunteers to perceive their total sleep time when compared with time measured by PSG. The data reinforce the influence of sleep deprivation on sleep perception.     

Effects of lithium on dopamine behavioural supersensitivity induced by rapid eye movement sleep deprivation

The effects of lithium on the potentiation of d-amphetamine-induced hyperlocomotion were evaluated in rapid eye movement (REM) sleep deprived rats. Under control conditions, pretreatment with lithium during 7 days did not modify the hyperlocomotion produced by d-amphetamine. REM sleep deprivation induced a pronounced potentiation of the locomotor response to d-amphetamine. In a stress control group this potentiation also occurred, but to a lesser degree than in the REM sleep deprived group. Lithium pretreatment prevented the increased response to d-amphetamine in both REM sleep deprived and stress control animals. The effects of lithium in REM sleep deprived rats are in accordance with reports that lithium is able to prevent the development of dopamine receptor supersensitivity. However, it cannot be excluded that in both REM sleep deprived and stress control groups the increased response to d-amphetamine is related to noradrenergic changes and/or noradrenergic-dopaminergic interactions. REM sleep deprivation seems to be an interesting model to study the underlying mechanisms of manic-depressive illness.     

REM phase deprivation and schizophrenia II.

Nine schizophrenic patients with active symptomatology were compared with seven patient controls in their response to two nights of rapid eye movement (REM) sleep deprivation. The control subjects demonstrate "normal" increases in total REM and percentage REM time increase on recovery nights compared to base line nights. The schizophrenic subjects differ substantially from the control subjects in both these measurements and show no perceptible change from base line nights on recovery nights. The effects of medication, anxiety, sleep loss, ceiling effects, and intensity change were not considered adequate to account for the above results. However, many questions, such as the specificity of this rebound failure to the schizophrenic patients and the possibility of a sleep disturbance factor operating independently of psychiatric diagnosis, remain to be answered.     

Increases in avoidance responding produced by REM sleep deprivation or serotonin depletion are reversed by administration of 5-hydroxytryptophan

Our objective was to directly compare the effects of rapid eye movement (REM) sleep deprivation (REMSD) and serotonin 5-hydroxytryptamine (5-HT) depletion on free-operant avoidance behavior in rats. These experiments were designed to determine if declining 5-HT levels observed during REMSD might mediate the increases in avoidance responding observed in REM sleep deprived rats. Rats were trained on a free-operant avoidance task. Following training, the animals were assigned to one of three sleep conditions (REMSD, tank control, or cage control). Animals in each sleep condition were exposed to four 5-HT manipulations: (a) saline plus saline; (b) p-chlorophenylalanine (PCPA) plus saline; (c) saline plus 5-hydroxytryptophan (5-HTP) and (d) PCPA plus 5-HTP. Both REMSD and 5-HT depletion via PCPA resulted in an increase in avoidance responding that was reversed by administration of 5-HTP. REMSD and 5-HT depletion via PCPA resulted in increased avoidance efficiency and were reversed by 5-HTP administration, but only changes following PCPA injection were statistically significant. Decreases in 5-HT levels that occur during REMSD likely mediate increases in avoidance responding.     

Effect of partial sleep deprivation on sleep stages and EEG power spectra: evidence for non-REM and REM sleep homeostasis.

The effect of repeated partial sleep deprivation on sleep stages and sleep EEG parameters was investigated in young subjects. After 2 baseline nights (B1, B2) of 7.5 h, sleep was restricted for 2 nights (D1, D2) to the first 4 h of the habitual bedtime period. Two recovery nights (R1, R2) with 7.5 h sleep followed. During the deprivation nights, stages 1 and 2 and REM sleep were reduced, while slow wave sleep (SWS; stages 3 and 4) was not significantly affected. However, the time integral of EEG power density in the range of 0.75-4.5 Hz (slow wave energy) was reduced. In the recovery period, SWS showed an enhancement in R1, and REM sleep showed a rebound in R1 and R2. An increase of REM sleep in the early part of the sleep period was evident in R1. Sleep latency was reduced in D2, R1 and R2. In accordance with the 2-process model of sleep regulation, EEG power density in non-REM sleep in the range of 0.75-4.5 Hz (slow wave activity) was only slightly higher in D2 and R1 than in baseline. An enhancement of slow wave activity in REM sleep was present in D2. Power density in the frequency range of 13-16 Hz was reduced in non-REM sleep (R1), SWS (R2) and stage 2 (R1). The results show (1) that the moderate reduction of slow wave energy in the deprivation nights induces only a minor enhancement of slow wave activity during recovery sleep; and (2) that a REM sleep deficit gives rise to an immediate rebound when 'slow wave pressure' is low.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of scopolamine on sleep and mood in depressed patients with a history of alcoholism and a normal comparison group.

In order to determine the effect of an anticholinergic agent on mood and sleep, scopolamine (0.4 mg IM) was administered before bedtime for three consecutive nights to 10 depressed patients (8 with a history of alcohol abuse) and 10 normal comparison subjects. The patients had a small, statistically significant antidepressant response on the second morning of treatment. Scopolamine inhibited rapid eye movement (REM) sleep and prolonged REM latency equally in depressed patients and the normal comparison group. Partial tolerance to the REM inhibiting effect of scopolamine developed between the first and third night of treatment. A REM rebound occurred during recovery nights. These results are consistent with concepts relating central cholinergic mechanisms to the control of REM sleep. Compared with controls, patients showed a greater increase in Stage 2 and Stage 2% and a lesser and increase in Delta (Stage 3 and 4) sleep % and Stage 4% on the first night of treatment. Further, well-controlled studies are needed to determine whether anticholinergic drugs possess clinically significant antidepressant effects.     

The effect of placebo administration on the first-night effect in healthy young volunteers

The first-night effect is a well-known phenomenon that is considered to result from a subject's lack of adaptation to the unfamiliar environment of a sleep laboratory and to the technical equipment used for polysomnography. The effect has been explored as a laboratory model for transient insomnia. The main characteristics of this effect are short total sleep time (TST) and rapid eye movement (REM) sleep, a lower sleep efficiency index, and longer REM sleep latency. Previous studies have reported that personality traits (such as trait anxiety) are a potential cause of the first-night effect and that the placebo effect is closely related to the anxiety levels of the subjects. To the best of our knowledge, there are no reports regarding the effects of a placebo on first-night sleep. This omission can be explained by the fact that the polysomnographic recordings obtained during the first night of a study are generally excluded from the analysis in order to avoid the inclusion of the first-night effect. In the present study, 8 male university students were subjected to polysomnographic examinations during drug-free, placebo-administration, and benzodiazepine-administration conditions in order to clarify the placebo effect on sleep during consecutive nights, particularly on the first night. The recordings for each condition were conducted for 4 consecutive nights. A placebo or 5 mg nitrazepam was administered at 2230 h using a double-blind crossover design, while no drug was administered during the drug-free condition. There was a 10-day interval between the examination of each condition. Polysomnographic recording was started at 2300 h and continued until the natural awakening of the subjects on the next morning. Subsequently, the subjects were requested to fill in a rating scale that is used to evaluate the subjective perception of sleep. An increase in stage-2 sleep associated with the first-night effect was observed on the first night during the drug-free and placebo-administration conditions. However, REM sleep reduction associated with the first-night effect was detected on the first night during the drug-free condition; this decrease in REM sleep was counteracted by the placebo during the placebo-administration condition. The nitrazepam, but not the placebo, decreased both slow-wave sleep (SWS) and REM sleep. The values for the tendency to fall asleep, feeling refreshed upon awakening in the morning, and the tension upon awakening in the morning were improved to a greater extent by the placebo and nitrazepam administrations than when no drug was administered. These results demonstrate the possibility that placebo administration may have a hypnotic/anxiolytic effect and may improve transient insomnia without causing SWS and REM sleep reductions.     

REM sleep deprivation during 5 hours leads to an immediate REM sleep rebound and to suppression of non-REM sleep intensity.

Nine healthy male subjects were deprived of REM sleep during the first 5 h after sleep onset. Afterwards recovery sleep was undisturbed. During the deprivation period the non-REM EEG power spectrum was reduced when compared to baseline for the frequencies up to 7 Hz, despite the fact that non-REM sleep was not experimentally disturbed. During the recovery interval a significant rebound of REM sleep was observed, which was only accompanied by a very slight increase of power in the lower non-REM EEG frequencies. In order to control for intermittent wakefulness, the same subjects were subjected to non-REM sleep interruption during the first 5 h after sleep onset 2 weeks later. Again subsequent recovery sleep was undisturbed. The interventions resulted in a similar amount of wakefulness in both conditions. During the intervention period, the non-REM EEG power spectrum was only marginally reduced in the delta frequency range. REM sleep duration was only slightly reduced. During the recovery interval, however, a substantial increase in EEG power in the delta frequency range was noted, without notable changes in REM time. It is concluded that an increased pressure for REM sleep results in longer REM episodes and a reduced intensity of non-REM sleep.     

Acute sleep deprivation reduces amygdala-kindled seizure thresholds in cats

It is well known that sleep loss activates human and experimental epilepsy. Because sleep deficits are also common among epileptics, it is possible that sleep loss enhances seizures by worsening these spontaneous sleep abnormalities. We examined this hypothesis by documenting the effects of acute (72 h) sleep deprivation on seizures in fully kindled cats. We have reported elsewhere sustained decrements in both slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep with the development of amygdala kindling in this species. In the present experiment, eight cats underwent an A₁ B₁ A₂ paradigm in which sleep state physiology (12-h polygraphic recordings) and seizure thresholds were examined in both an experimental (sleep deprivation) and control (nonsleep deprived) sequence of conditions, with order of presentation counterbalanced. Sleep deprivation was produced by a modification of the “flower pot” procedure and involved placing the cat on a small platform over water so as to prevent REM sleep. In the control sequence, cats underwent the same procedure except the platform was large enough to allow normal SWS and REM sleep. A significant reduction in both REM and SWS sleep occurred exclusively during the experimental B₁ condition and was accompanied by a significant reduction in seizure threshold for partial or generalized tonic-clonic convulsions. These findings indicated that this procedure, thought to influence only REM sleep, also disrupts SWS; further, this generalized disruption of sleep reduced kindled seizure thresholds, perhaps by compounding existing sleep deficits. Collectively, these observations again suggest that the integrity of both SWS and REM sleep may be an important consideration in the etiology of amygdala-kindled seizures.     

Shorter REM latency associated with more sleep cycles of a shorter duration in healthy humans

A significant association between rapid eye movement (REM) sleep latency and the number of non-REM/REM sleep cycles was found 15 years ago in a large retrospective study. The present prospective study further explored this intra-sleep relationship and analyzed the links between these two variables and the mean cycle duration. It was based on a carefully selected group of healthy control subjects whose sleep was polysomnographically recorded at home for 4 sequential nights. The latency of REM sleep was inversely correlated with the number of cycles and positively correlated with the mean cycle duration, both in individual nights and on means of 4 nights. The present study demonstrated that variations in the number of cycles or the mean cycle duration between the nights are far less important than the substantial differences observed between subjects. Present outcomes support the study of sleep cycle periods and frequencies in those psychiatric disorders where REM sleep latencies have been found to be shorter, and they suggest that these variables be included in sleep studies in which cycles are compared with each other.     

Sleep deprivation: effect on sleep stages and EEG power density in man

Sleep was analysed in 8 young adults subjects during two baseline nights and two recovery nights following 40.5 h sleep deprivation. Sleep stages were scored from the polygraph records according to conventional criteria. In addition, the EEG records of the entire nights were subjected to spectral analysis to compute the frequency distribution of the power density in the 0.25-25 Hz range for 0.5 Hz or 1.0 Hz bins. In the first recovery night, the power density in the delta band was significantly higher than baseline for total sleep time as well as for sleep stages 2, 3 and 4, 4 and REM. These changes were not restricted to the delta band, but extended to higher frequency bands. Minor, but significant, effects of sleep deprivation were seen in the power density distribution of the second recovery night. In the baseline nights, a progressive reduction of power density in the delta/theta range was present for successive non-REM-REM sleep cycles for total sleep time and stages 2, 3 and 4, and 4. The results show that effects of sleep deprivation as well as trends within the sleep periods are readily apparent from spectral analysis, but are inadequately reflected by conventional sleep scoring. When the power density values were integrated over the entire frequency range (0.75-25 Hz) for each non-REM-REM sleep cycle, an exponential decline from cycle 1 to cycle 3 was suggested. The present findings support the hypothesis that the EEG power density in the low frequency range is an indicator of a progressively declining process during sleep whose initial value is determined by the duration of prior waking.     

Effects of REM sleep awakenings and related wakening paradigms on the ultradian sleep cycle and the symptoms in depression

In 1975 Vogel and coworkers published their classical study where they compared selective rapid eye movement (REM) sleep deprivation by brief awakenings to a control intervention paradigm in depressed patients. The superior antidepressive impact of the first procedure was attributed to the REM pressure accumulating during the treatment period. The laborious procedure and the considerable effort necessary to evaluate the sleep profiles in real time have prevented similar experiments so far. Based on artificial neural networks we developed a software for the real time detection of REM sleep. In combination with an alarm system the algorithm allowed us to wake up subjects automatically and to reduce REM sleep by about 50%. The procedure was then compared to a modified nonREM intervention paradigm for a treatment period of ten consecutive nights in depressed patients (n(1)=14, n(2)=13). These simultaneously received moderate dosages of Trimipramine. We found a strong and robust but not significantly different reduction of the average Hamilton rating scores (33 and 41% of baseline levels). While the REM sleep awakenings shortened the sleep cycle duration considerably, our nonREM intervention paradigm lengthened the ultradian alternations. Both effects might be interpreted as a challenge imposed on the nonREM-REM alternating mechanism possibly responsible for the antidepressive impact. A different timing of the control interventions might have caused the discrepancy between our findings and those of Vogel and coworkers.     

REM sleep in primary depression: a computerized analysis.

REM sleep in 35 inpatients with primary depression was automatically analyzed for 7 consecutive nights during placebo administration. For the total night of sleep, as well as each individual REM period, the number of REMs, their total voltage integral over time, the sum of their durations and the average REM size were automatically calculated. Validity of these automated REM measures was established by significant correlations with manually scored REM measures. Changes in REM sleep across the night were also investigated. Similar to findings in normal subjects, REM time did not change from REM period to REM period. Average REM size increased significantly from REM period 2-3 and 3-4. Contrary to what is seen in normal subjects, REM frequency was high during the first REM period, significantly decreased from the first to second REM period and then remained constant. Finally, a significant inverse correlation between REM frequency for the first REM period and REM latency was noted. This pattern of REM sleep is interpreted as indicating a high pressure for phasic REM at the beginning of the night which is dissipated by the first REM period.     

Platform sleep deprivation affects deep slow wave sleep in addition to REM sleep

Rats were sleep deprived by the platform method to look for differential effects on light and deep slow wave sleep depending on platform size. Diameters of large and small platforms were 15 cm and 5.1 cm respectively. Sleep was recorded during a baseline light period (09.00-19.00 h), continuously during 48 h of sleep deprivation and during the first lights on recovery period (09.00-19.00 h). In both platform conditions REM sleep was virtually abolished during the first light period (hours 0-10 of sleep deprivation), while NREM sleep was reduced to approximately half of control values. During the second light period (hours 22-34 of sleep deprivation) REM sleep recovered somewhat in the large platform group. Light slow wave sleep (SWS-1) was comparable to baseline while deep slow wave sleep (SWS-2) was still significantly reduced. In the small platform group both SWS-2 and REM sleep was considerably reduced on day 2. Over the whole deprivation period there was an effect of platform size on SWS-1 (higher in the small platform group), and on SWS-2 and REM sleep (lower in the small platform group). During the 9 h light-time recovery sleep there was an REM sleep rebound in both groups. SWS-1 was reduced in both groups while SWS-2 was not significantly increased. The ratio SWS-2/SWS-1 was, however, significantly increased only in the small platform group recovery sleep. The results suggest that platform sleep deprivation deprives the animals of deep slow wave sleep in addition to REM sleep. This has implications for conclusions on REM sleep function based upon REM sleep deprivation.     

A psychophysiological investigation of the short-term effects of clozapine upon sleep parameters of normal young adults.

A nine consecutive night, double-blind design was used to assess the effects of a psychotropic agent (clozapine) upon sleep parameters as well as measures of mood and performance in a group of seven normal, young adults. Placebo was administered to a control group of seven subjects. EEGs and EOGs were monitored throughout the night in a laboratory environment and were scored according to standardized criteria. The administration of 25 mg clozapine/night for three consecutive nights significantly reduced stage 4 sleep on the second and third nights. Whereas stage REM sleep was not affected, a variety of REM indices were significantly increased on the third night of clozapine administration and/or on the first night of clozapine withdrawal. The number of body movements and the number of body movements/minute of sleep were significantly reduced on the three nights of clozapine administration. Numerous psychophysiological side effects were reported. These results indicate that clozapine may be a useful medication in the treatment of sleep disorders. However, the incidence of adverse side effects of represents a major limitation in the use of clozapine as an hypnotic agent at the dose-rate employed.     

Sleep onset REM periods observed after sleep interruption in normal short and normal long sleeping subjects

Among about 1000 male college students, 6 short and 5 long sleepers were finally selected on the basis of their responses to a sleep habit questionnaire. The subjects slept in the laboratory for 6 consecutive nights. On nights 4, 5 and 6, deliberate sleep interruption was performed during the second sleep cycle. During interruption, subjects were asked to perform 3 different kinds of tasks on each of the 3 nights. Stage REM latencies after interruption were distributed bimodally with peaks at sleep onset after the interruption (sleep onset REM period: SOREMP) and 50-60 min later (non-SOREMP). SOREMPs were observed only in the sleep of short sleepers. Short sleepers showed a shorter sleep latency and a greater amount of stage REM in the 2nd and the 3rd sleep cycle of their baseline sleep record than did long sleepers. These characteristics of short sleepers' sleep and sleep interruptions probably affected the occurrence of SOREMPs. The mean duration of SOREMPs was significantly shorter than that of non-SOREMPs.     

A polysomnographic study of sleep patterns in normal humans with low- or high-anxiety personality traits

To clarify the effects of anxiety-related personality traits on sleep patterns, polysomnographic examinations (PSG) were performed over 4 consecutive nights on normal humans who tested within the low- or high-anxiety ranges. The subjects consisted of two groups of six male university students who scored either less than 45 points (low-anxiety group) or more than 55 points (high-anxiety group) on the Spielberger's State Trait Anxiety Inventory. Compared to the levels of sleep change in the high-anxiety group, the low-anxiety group exhibited a greater change in REM sleep and stage 2 sleep. The REM sleep in the low-anxiety group was shorter on the first and second nights compared to the third and fourth nights, and the stage 2 sleep was longer on the first night than on the remaining three nights. Thus, the low-anxiety group showed a first-night effect followed by partial recovery on the second night, while the high-anxiety group exhibited no obvious first-night effect. These results suggest that there is a difference in sleep patterns, assessed by consecutive PSG, between those with low- and high-anxiety traits, and that anxiety-related personality traits attenuate the occurrence of the first-night effect, reflecting a lower adaptability to a novel environment.     

Intracortical inhibition and facilitation upon awakening from different sleep stages: a transcranial magnetic stimulation study

Intracortical facilitation and inhibition, as assessed by the paired-pulse transcranial magnetic stimulation technique with a subthreshold conditioning pulse followed by a suprathreshold test pulse, was studied upon awakening from REM and slow-wave sleep (SWS). Ten normal subjects were studied for four consecutive nights. Intracortical facilitation and inhibition were assessed upon awakening from SWS and REM sleep, and during a presleep baseline. Independently of sleep stage at awakening, intracortical inhibition was found at 1-3-ms interstimulus intervals and facilitation at 7-15-ms interstimulus intervals. Motor thresholds were higher in SWS awakenings, with no differences between REM awakenings and wakefulness, while motor evoked potential amplitude to unconditioned stimuli decreased upon REM awakening as compared to the other conditions. REM sleep awakenings showed a significant increase of intracortical facilitation at 10 and 15 ms, while intracortical inhibition was not affected by sleep stage at awakening. While the dissociation between motor thresholds and motor evoked potential amplitudes could be explained by the different excitability of the corticospinal system during SWS and REM sleep, the heightened cortical facilitation upon awakening from REM sleep points to a cortical motor activation during this stage.     

Electroencephalographic sleep in mania

Electroencephalographic (EEG) sleep patterns were examined in nine unmedicated patients meeting DSM-III-R criteria for a current manic episode (four men and five women) for two to four consecutive nights. Compared with age- and sex-matched normal control subjects, manic patients exhibited significantly decreased total recording period, decreased time spent asleep, increased time awake in the last two hours of recording, shortened rapid eye movement (REM) latency, increased REM activity, and increased REM density. These results suggest that mania is associated with marked disturbances of sleep continuity and REM measures. Sleep continuity and REM sleep abnormalities of a similar nature and degree have been reported in major depression and psychotic depression. Thus, it is possible that various forms of affective disorders and psychotic disorders have pathophysiologic mechanisms in common.