Cholinergic REM sleep induction response correlation with endogenous major depressive subtype

We compared central cholinergic responsiveness (using the latency to induction of rapid eye movement sleep after arecoline challenge as a response marker) in 90 subjects: patients with major depressive disorder (MDD) (n = 53), nonaffective psychiatric controls (n = 17), and normal controls (n = 20). MDD patients as a whole showed a supersensitive cholinergic response compared to nonaffective patients and normal subjects. Further analysis indicated a strong association between cholinergic supersensitivity and endogenous subtype of MDD, including a significant correlation with specific endogenous features such as distinct quality of mood, anhedonia, lack of reactivity, and agitation. Unlike rapid eye movement (REM) latency (a more conventional physiological marker), cholinergic sensitivity did not correlate with age or severity of illness but only with the presence of endogenous features. Previously described sleep physiological correlates such as REM latency and REM density of the first REM period also distinguished between endogenous and nonendogenous MDD. There was a statistically significant correlation between REM latency and arecoline REM induction response.     

Changes in REM sleep occurrence due to rhythmical auditory stimulation in the rat

The effects of the rhythmical delivery of an auditory stimulus (1000 Hz, from 50 to 100 dB, 20 ms, every 20 s) on the pattern of rapid eye movement (REM) sleep occurrence was studied in the rat. The stimulation was simultaneously carried out on pairs of rats over 5 consecutive days (10-h recording sessions), during which a tone of increasing intensity (50, 63, 75, 88, 100 dB) was used. In each experimental session, auditory stimulation was triggered by the REM sleep occurrence of one rat (REMS-selective stimulation) whilst the other rat simultaneously received the same stimuli, but during any stage of the wake-sleep cycle (REMS-unselective stimulation). The results showed that the total amount of REM sleep in the 10-h recording session was increased over the 5 days of stimulation in the REMS-unselective group. This effect was due to an increase in the mean duration of REM sleep episodes. However, no significant changes were observed in animals under REMS-selective stimulation, nor in a third group of animals in which the spontaneous evolution of REM sleep occurrence (REMS-spontaneous) was studied. Since 86% of the stimuli under the REMS-unselective auditory stimulation fell outside REM sleep, the result would suggest that REM sleep occurrence is affected when the stimuli are delivered during a time period (i.e. during wakefulness or non-REM sleep) in which it is well known that physiological regulations are fully operant.     

Increasing PGO spike density by auditory stimulation increases the duration and decreases the latency of rapid eye movement (REM) sleep

The purpose of this study was to determine whether ponto-geniculo-occipital (PGO) spikes play a role in triggering or maintaining sleep. During the recording of the sleep cycle of cats, the appearance of the first PGO spike automatically triggered an auditory stimulus through a speaker placed in the cat's recording cage. The effect of this procedure was compared to similar period when no such stimulus was given. The results showed that the auditory stimulus increased PGO spike density during REM sleep. It also produced a spectacular increase in the duration of REM, while decreasing the latency of its appearance from the first PGO spike. It is suggested that the auditory stimulus reinforces the 'PGO system', which in turn may function as a pace-setter for priming and maintaining REM sleep.     

REM sleep enhancement induced by sensory stimulation is prevented by kainic acid lesion of the pontine reticular formation

It has been shown that auditory or somatic stimulation during rapid eye movement (REM) sleep is capable of producing a significant increase in ponto-geniculo-occipital (PGO) spike density as well as in REM sleep duration. The purpose of this study was to determine the role of the medial pontine reticular formation (PRF) in mediating such increase of REM sleep duration. After a baseline recording whereby on the same recording day the control and the stimulus (auditory or somatic) alternated with each REM, a group of cats was lesioned with kainic acid in the PRF. The sleep-wake cycle was recorded again on days 15, 30 and 45 post-lesion, following the same procedure. The results showed no changes in REM sleep duration and PGO spike density in the lesioned animals. However, when sensory stimulation was applied it was ineffective in producing REM sleep enhancement, although it was able to increase PGO spike density. These findings suggest that the effects of sensory stimulation on REM sleep duration are accomplished through the PRF, probably by inducing an increase in the excitability levels of such neurons, and further suggests that PGO spike density and REM duration are independent of each other.     

Circadian rhythms of melatonin and peripheral clock gene expression in idiopathic REM sleep behavior disorder

ObjectiveTo evaluate changes in the expression of clock genes and melatonin levels in patients with idiopathic REM sleep behavior disorder (RBD) as a potential early stage of synucleinopathies.MethodsWe assessed the rhythmicity of circadian clock genes using real time-quantitative polymerase chain reaction and 24-h blood melatonin profiles using radio-immunoassay in 10 RBD patients and nine age-matched controls.ResultsThe RBD patients did not show circadian rhythmicity for clock genes Per2, Bmal1, and Nr1d1 but the rhythmicity of Per 1 remained, and the amplitude of Per3 was diminished. The 24-h melatonin rhythm did not differ between RBD patients and healthy control subjects. Melatonin profile in RBD patients was delayed by 2 h compared to controls, the habitual sleep phases were phase delayed by about 1 h, however no phase shift occurred in any of the clock genes studied. The control group had stable acrophases of melatonin rhythms of approximately 5 h whereas the RBD patients had a more dispersed range over 11 h.ConclusionsOur results suggest that RBD could be associated with altered expression of clock genes and delayed melatonin secretion. Thus, we argue that circadian system dysregulation could play a role in RBD.     

Homozygous Machado–Joseph disease presenting as REM sleep behaviour disorder and prominent psychiatric symptoms

A male patient carrying the homozygous gene for Machado-Joseph disease (MJD) presented at age 43 with sleep disturbances and psychiatric symptoms followed by ataxic speech and gait. A polysomnogram (PSG) showed decreased rates of sleep time and stage rapid eye movement (REM) and an increased rate of 'stage 1-REM with tonic EMG' (Tachibana et al., 1975); all compatible with REM sleep behaviour disorder (RBD). Molecular gene analysis at age 59 showed that the CAG repeat units in the MJD gene were 60 and 60, smaller than the reported lengths for homozygous MJD patients (63-70 and 66-72). In addition to sleep disturbances, in particular RBD, psychiatric symptoms may be important clinical features in both heterozygous and homozygous MJD.     

Daytime sleep patterns of primary depressives: A morning nap study

The electroencephalographic sleep patterns of 10 primary depressives were recorded during baseline nights and two morning nap sessions using a fixed time schedule. Averaged sleep measures for baseline nights replicated previous findings of altered rapid eye movement (REM) sleep patterns and sleep continuity. REM sleep during morning naps occurred only in patients with elevated REM indexes on baseline and prenap nights; it failed to appear in morning sleep of patients who exhibited contrasting REM characteristics. An analysis of hourly REM sleep distribution and averaged deviations from group means revealed significant differences between the two groups which could account for the uneven daytime REM propensity.     

Cholinergic brainstem mechanisms of REM sleep in the rat

Injection of carbachol into the brainstem of rats produced an increase in rapid eye movement (REM) sleep which was site- and dose-dependent. Effective locations for carbachol to stimulate REM sleep included the pontine reticular formation at the level of the trigeminal motor nucleus and the dorsal parabrachial area in the caudal midbrain. The carbachol effect in the caudal pons was dose-dependent. Additionally, this effect was blocked by concomitant administration of the muscarinic antagonist atropine. Control experiments suggested that the drug-induced phenomenon appeared to be an increase in normal physiological REM sleep.     

Senior Vipassana Meditation practitioners exhibit distinct REM sleep organization from that of novice meditators and healthy controls

Abstract/Summary

The present study is aimed to ascertain whether differences in meditation proficiency alter rapid eye movement sleep (REM sleep) as well as the overall sleep-organization. Whole-night polysomnography was carried out using 32-channel digital EEG system. 20 senior Vipassana meditators, 16 novice Vipassana meditators and 19 non-meditating control subjects participated in the study. The REM sleep characteristics were analyzed from the sleep-architecture of participants with a sleep efficiency index?>85%. Senior meditators showed distinct changes in sleep-organization due to enhanced slow wave sleep and REM sleep, reduced number of intermittent awakenings and reduced duration of non-REM stage 2 sleep. The REM sleep-organization was significantly different in senior meditators with more number of REM episodes and increased duration of each episode, distinct changes in rapid eye movement activity (REMA) dynamics due to increased phasic and tonic activity and enhanced burst events (sharp and slow bursts) during the second and fourth REM episodes. No significant differences in REM sleep organization was observed between novice and control groups. Changes in REM sleep-organization among the senior practitioners of meditation could be attributed to the intense brain plasticity events associated with intense meditative practices on brain functions.     

Modification of REM sleep and associated phasic activities by protein synthesis inhibitors

The sleep-wake cycle and multiple-unit activity following the administration of various doses of protein synthesis inhibitors was studied in unrestrained cats. Special care was taken to analyze the effects of those drugs on phasic and tonic rapid eye movement (REM) sleep periods. It was observed that protein synthesis inhibitors decreased specifically total REM sleep time, at the expense of wakefulness, without altering slow-wave sleep time. It was further noted that the reduction in REM sleep was the result of a decrease in the frequency of REM periods, rather than in the duration of each individual period. In addition, protein synthesis inhibitors decreased phasic REM sleep and notably prolonged tonic REM periods. Moreover the phasic bursts of multiple-unit activity normally seen during REM sleep in control recordings were practically absent during REM sleep after the administration of protein synthesis inhibitors. It is suggested that protein molecules may participate in the mechanisms which trigger REM sleep.     

Amphetamine abolishes REM sleep rebound in rats: effect of a single injection

Rats implanted with electrodes for polygraphic recording were deprived of REM sleep for 24 h. Following REM deprivation animals were injected with d-amphetamine (3 mg/kg, i.p.) and were polygraphically recorded for 48 h. The results show that administration of amphetamine abolished the initial 12 h of REM sleep rebound and that this loss of REM sleep was not regained during the entire 0–48 post-REM deprivation period.     

Comparison between eye movement latency and REM sleep parameters in major depression

Alterations of sleep can be observed polysomnographically in approximately 90 percent of depressed patients. Most of the registered sleep abnormalities in depression also occur in other psychiatric disorders. Only some types of REM sleep alterations – short REM latency, increase of REM density and shortening of mean latency of eye movements – were reported as more specific for affective disorders. In the present study polysomnograms of 21 medication free patients with major depressive disorder (assessed with a structured interview for DSM-III-R and Hamilton Scale) and 21 healthy controls were analysed. REM latency (LREM), REM density (RD), latencies of eye movements (LEM) and mean latency of eye movements (M-LEM) were calculated for both groups. Depressed patients (compared with healthy controls) showed increased RD (38.2% vs. 28.2%, p < 0.0001), shortened M-LEM (35.7 s vs. 48.3 s, p < 0.04) and shortening of LEM in the 1st (28.9 s vs. 48.9 s, p < 0.007) and 4th (27.0 s vs. 59.1 s, p < 0.043) REM sleep periods. LREM was not shortened significantly in depressives (78.5 min vs. 91.3 min, ns). In healthy subjects a negative correlation between M-LEM and RD was found (rho = − 0.47, p < 0.03). Since in the current study depressed patients differed from healthy controls, especially concerning phasic activity during REM sleep, presented data support the essential role of REM density for the assessment of sleep in depression. As a quick and easy manner to compute measurement, M-LEM is suggested as additional parameter for the assessment of phasic activity during REM sleep. Received: 23 March 1999 / Accepted: 23 November 1999     

Brain potentials associated with the onset and offset of rapid eye movement (REM) during REM sleep

The relationship between dreaming and rapid eye movements (REM) during REM sleep is still controversial. This study records the brain potentials time-locked to the onset and offset of REM in 11 healthy young volunteers. Before the onset of REM, no presaccadic readiness potential was found. Conversely, two positive potentials (P1 and P2) appeared following the offset of REM. The latter potentials were dominant in the parieto-occipital area. These findings suggest that REM is initiated without preparation but elicits some information-processing activities that were speculated to occur in the cortical visual area. The data support the activation-synthesis or association hypothesis of dreaming rather than the scanning hypothesis.     

GABAergic neurons in prepositus hypoglossi regulate REM sleep by its action on locus coeruleus in freely moving rats.

GABA in locus coeruleus modulates REM sleep. Apart from the presence of interneurons, locus coeruleus also receives GABAergic inputs from prepositus hypoglossi in the medulla, where the presence of REM-ON-like neurons have been reported. Therefore, it was hypothesized that GABAergic projections from prepositus hypoglossi to locus coeruleus may modulate REM sleep. The experiments were conducted on chronic rats prepared for recording EEG, EOG, and EMG in freely moving conditions. Bipolar stimulating electrodes were implanted in prepositus hypoglossi bilaterally, while chemitrodes were implanted bilaterally in locus coeruleus. The prepositus hypoglossi were bilaterally stimulated (3 Hz, 250 microsec, 100 microA) for 8 h in the presence and absence of picrotoxin (0.25 microg/250 nl) microinjection bilaterally in locus coeruleus, followed by poststimulation recording for 4 h. It was observed that stimulation of prepositus hypoglossi alone significantly increased REM sleep primarily by increasing the REM sleep duration per episode. However, when it was stimulated in the presence of picrotoxin in LC, REM sleep decreased, predominantly due to decreased REM sleep duration per episode. The results of this study suggest that GABAergic inputs from prepositus hypoglossi act on locus coeruleus and regulate REM sleep, possibly by inhibition of REM-OFF neurons.     

Human cerebral potentials associated with REM sleep rapid eye movements: links to PGO waves and waking potentials

Eye movement triggered averaging and topographic display techniques indicate the presence of parieto-occipital potentials that precede the rapid eye movements of human REM sleep. Since these potentials have strong similarities with PGO waves in animals, including lateralization according to eye movement (EM) direction, and with waking EM-antecedent potentials in man, this suggests that PGO-like activity both exists in man, and may be functionally related to EM-antecedent potentials in waking. The ability to detect such central potentials opens the possibility of studying REM sleep central physiological structure in a variety of normal and pathological conditions in humans.     

MHPG excretion and EEG sleep in primary depression

Measures of daily urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion and electroencephalographic (EEG) sleep data were examined in 30 patients hospitalized for depression. This sample (mean age = 35 years) comprised 17 females and 13 males, all of whom were drug-free for 2 weeks and met Research Diagnostic Criteria for primary depressive disorder. Data analyses were conducted on the entire group, as well as the male, female, unipolar, and recurrent subgroups. No significant relationships were observed between total MHPG excretion and rapid eye movement (REM) or non-REM sleep variables. In particular, the absence of an interrelatedness of MHPG and REM sleep fails to confirm earlier findings in a smaller patient sample. These results, therefore, raise new questions about the proposed role of central noradrenergic activity in the mediation of REM sleep in depression.     

Effect of preexisting borderline personality disorder on clinical and EEG sleep correlates of depression

Two groups of depressed patients were studied: (1) The first group comprised 15 inpatients who were diagnosed as predominantly “borderline personality disorders” based on DSM-III and psychometric test criteria; these patients were also clinically depressed. (2) The second group consisted of 18 inpatients who met Research Diagnostic Criteria (RDC) for major depressive disorder (MDD) but who failed to meet the above criteria for borderline personality disorder. Subsequent to the selection of patients for study, an independent diagnostic evaluation revealed that MDD patients with borderline personality disorder had higher ratings than nonborderline MDD patients on items from the Schedule for Affective Disorders and Schizophrenia such as total anxiety, anger, schizotypal features, miscellaneous psychopathology, and alcohol and drug abuse. A further breakdown of miscellaneous psychopathology items revealed greater subjective anger, self-pity, and demandingness in borderline patients. A comparison of RDC subtypes in the two groups revealed a significant increase in bipolar II diagnoses in the borderline MDD group. Electroencephalographic (EEG) sleep studies carried out in a subsample of MDD borderline (n=8) and primary MDD nonborderline (n=11) patients revealed no significant differences between the two groups. Thus, in contrast to the EEG sleep findings reported for secondary depression with other antecedent psychiatric disorders, the present study indicated that a preexisting diagnosis of borderline personality disorder in MDD patients did not alter the characteristics short latency of rapid eye movement (REM) sleep and the sleep continuity disturbances reported in primary MDD. These data confirm earlier reports by Akiskal (1981), Carroll et al. (1981), and McNamara et al. (1982) concerning the phenomenological and EEG sleep profiles of borderline patients.