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.     

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.     

Effect of short duration morning bright light in elderly men: sleep structure

Sleep structure was measured in five healthy elderly men in their homes. The subjects were exposed to bright light (6000 lx) for 30 min in the morning or instructed to sit in front of a desktop lighting device without light. Relative to the control conditions, bright light exposure significantly decreased time in bed and the number of awakenings. Rapid eye movement sleep was significantly fragmented by stage 1 sleep in the control condition compared with the bright light condition. These findings indicate that a short duration of morning bright light changes sleep structure and is effective in maintaining sleep.     

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.     

A community-based study of risk factors for probable rapid eye movement sleep behavior disorder

ObjectivesTo cross-sectionally explore the potential risk factors for rapid eye movement (REM) sleep behavior disorder (RBD) in a community cohort in Shanghai.MethodsBased on the validated RBD screening questionnaire (RBDSQ), we identified individuals with probable RBD (pRBD) in 3635 community-dwelling residents (≥50 years old) from an urban community of Shanghai. Potential risk factors of pRBD, including age, sex, smoking, socioeconomic status, obesity, consumption of tea (surrogate for caffeine intake) and alcohol, medications and chronic disease status, were assessed via questionnaire. We used logistic regression to investigate the associations between these studied factors and pRBD after adjusting for age, sex and other studied factors.ResultsBased on the RBDSQ score ≥5, 2.70% (3.28% in men and 2.41% in women) participants were considered as pRBD. We found that lower education, presence of head injury, atrial fibrillation, hyperlipidemia, constipation, olfactory disturbance, and imbalance, use of alcoholic beverage, selective serotonin reuptake inhibitor, and benzodiazepine were associated with higher likelihood of having pRBD (P < 0.05 for all). In contrast, male sex, use of coffee or tea, smoking and other factors were not significantly association with altered risk of having pRBD. We did not find significant interaction between sex, age and these factors, in relation to pRBD risk.ConclusionsIn this community-based study of older adults, we identified several potential risk factors for concurrent pRBD, including environmental factors and vascular risk factors.     

Cholinergic reduction of REM sleep duration is reverted by auditory stimulation

It was previously shown that an auditory stimulus given prior to and throughout a rapid eye movement (REM) sleep period was capable of inducing a significant increase in REM sleep duration and pontogeniculo-occipital (PGO) spike density. The purpose of this study was to determine whether the increase in REM duration is dependent on PGO spike density. We administered atropine to cats at doses of 0.1–0.6 mg/kg and the effects on REM duration and PGO spikes was determined. The doses of 0.2 and 0.3 mg/kg of atropine were then utilized to compare REM sleep periods with and without auditory stimulation. The results showed that both REM duration and PGO spikes were decreased by atropine, but could be dissociated from each other depending on the doses. In addition, it was shown that the auditory stimulus protected the animals from the effects of atropine but only in relation to REM sleep duration. The results indicate that both REM sleep duration and PGO spikes have a cholinergic component and that the auditory stimulus exerts its REM enhancing properties in a manner which seems to be independent of the PGO spike density. The results are discussed in terms of receptor availability and/or excitability levels of medial reticular neurons.     

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.     

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.     

Clonidine effects on all-night human sleep: opposite action of low- and medium-dose clonidine on human NREM-REM sleep proportion

Norepinephrine (NE) is considered to play a permissive role in the occurrence of rapid eye movement (REM) sleep. Clonidine is an NE alpha-2-receptor agonist, which has been considered to act mainly on the autoreceptors of presynaptic noradrenergic neurons to reduce their release of NE. However, previous studies of clonidine effects on REM sleep have produced controversial results and the effects of clonidine remain uncertain. To clarify the pharmacological effects of clonidine on human sleep, the sleep electroencephalograms (EEG) recorded from 15 young normal subjects after a single administration of either a low (25 micro g) or medium (150 micro g) dose of clonidine were examined, and fast Fourier transformation (FFT) spectral analyses of the C3-A2 EEG were performed. Low-dose clonidine significantly increased the amount of REM sleep and decreased the amount of non-REM (NREM) sleep during the second one-third of the drug nights compared to the corresponding hours of baseline night recordings. In contrast, medium-dose clonidine significantly decreased REM and increased NREM on drug nights compared to baseline nights in the entire night. The opposite actions of low and medium doses of clonidine on NREM-REM proportion may indicate that low-dose clonidine mainly affects the alpha-2-receptors on locus coeruleus-NE neurons presynaptically, reducing the release of NE, whereas medium-dose clonidine acts more post-synaptically.     

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     

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.     

Multivariate study of sleep EEG in depression

The effects of four subtypes of major depressive disorder on four sleep EEG variables obtained in 153 depressed inpatients were analyzed taking into account the effects of age, gender, DST response and severity of depression. We have found that age significantly affected slow wave sleep. Sleep efficiency and total sleep time were shown to vary with age and severity of depression. Such effects were not detected for REM latency which was influenced by the endogenous subtype and the gender. Our data indicate that in depressed patients sleep EEG measures are influenced by multiple factors.     

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.     

Muscarinic supersensitivity: A possible model for the sleep disturbance of primary depression?

The sleep changes induced in normal volunteers following the administration of scopolamine on 3 consecutive mornings resemble many of the abnormalities observed in the sleep of patients with primary depression: increased sleep latency and reduced rapid eye movement (REM) latency, total sleep time, and sleep efficiency. Furthermore, in a multivariate discriminant analysis--previously shown to distinguish the sleep records of depresed patients from those of normal controls and insomniac patients--the records from baseline nights were selected as normal and those after scopolamine as predominately depressed. Those observations suggest to us that muscarinic supersensitivity in normals may function as a pharmacological model for the sleep disturbances of depression.     

REM sleep and cortisol response to the cholinergic challenge with RS 86 in normals and depressives

The influence of the muscarinic agonist RS 86 on rapid-eye-movement (REM) sleep and on hypothalamic-pituitary-adrenocortical (HPA) axis was studied in healthy subjects and in patients with a major depression. In both groups, RS 86 induced a shortening of REM latency and an increase in REM sleep; these effects were more pronounced in the depressives than in the controls. This finding supports the assumption that in depression the REM sleep regulating neurons are hypersensitive to cholinergic stimuli. However, neither in the healthy subjects nor in the depressed patients was an RS 86 induced increase in plasma cortisol seen. This observation does not agree with the assumption that, in humans, the HPA axis is stimulated by muscarinic neurons and that hypercortisolemia in depression is due to an overactivity of muscarinic neurons activating the HPA axis.     

Cat sleep: A unique first night effect

Longitudinal sleep studies in chronically implanted cats revealed a unique first night effect. Unlike other species, during the first 24 hr of sleep recording, the electroencephalogram and reticular formation multiple unit activity revealed more rapid eye movement sleep occurred than during subsequent 24 hr recording sessions. In addition, higher rapid eye movement to slow wave sleep ratios were observed for the first 24 hr as compared to the following days. An increase in wakefulness and decrease in slow wave sleep occurred on the third recording day as compared to the initial 24 hr period. These data have important implications for studies of variables on the sleep pattern of animals.     

Effect of chronic intracerebroventricular infusion of cholecystokinin on respiration and sleep

We investigated the effect of chronic intracerebroventricular infusion of the sulfated cholecystokinin octapeptide (CCK-8S) on sleep pattern and respiratory rate. The results indicate a depression of respiratory rate during Non-REM and REM sleep as well as an increase in the number of REM periods occurring per hour of Non-REM sleep. It is suggested that central release of CCK-8S is capable of modulating the automatic regulation of respiration during sleep and altering the normal sleep-waking pattern.