Shorter Rapid Eye Movement Sleep Research Articles

Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics Study.

Sleep patterns are more frequently interrupted in patients with Parkinson's disease (PD), and it is still unclear whether genetic factors are involved in PD-related sleep disorders. In this study, we hypothesize that PD-associated genetic risk affects lipid metabolism, which in turn contributes to different types of sleep disorders. We used a non-targeted lipidomics to explore the lipid composition of cerebrospinal fluid (CSF) exosomes derived from patients with PD carrying phospholipase A2 Group VI (PLA2G6) and sphingomyelin phosphodiesterase 1 (SMPD1) mutations. PLA2G6 mutations (c.1966C>G, Leu656Val; c.2077C>G, Leu693Val; c.1791delC, His597fx69) significantly increase the exosomal content of glycerophospholipids and lysophospholipids, specifically phosphatidylcholine (PC) and lysophosphatidylcholine (LPC). Exosome surface presence of melatomin receptor 1A (MTNR1A) was detectable only in patients with PLA2G6 mutations. We have further shown that, in patients with PD carrying PLA2G6 mutations, sleep latency was significantly longer compared to those carrying WT PLA2G6, and we speculate that functional PLA2G6 mutations lead to structural changes and lipid deregulation of exosomes, which in turn alters exosomal cargo and affects PD-related sleep disorders. In SMPD1, G508R variant-carrying patients with PD abundance of sphingomyelins was significantly higher and had significantly shorter rapid eye movement sleep. Our study demonstrated that the disturbed composition and function of CSF-derived exosome lipidome during the pathological stage of PD may affect different types of sleep disorder in PD.

0882 The Longitudinal Relationship between Objective Sleep and Cardiovascular Parameters During Pregnancy

Abstract Introduction Growing evidence shows the important role of sleep on cardiovascular health in pregnant women with nearly 50% self-reporting poor sleep quality and 30% insufficient sleep. These sleep disturbances have been associated with adverse perinatal outcomes (e.g., hypertension, preterm births). Many studies have only used self-reported questionnaires during pregnancy. However, a few studies have utilized sleep labs and found that subjective and objective assessments of sleep varied from poor to low associations. The aim of this study was to examine the longitudinal relationship between objective sleep and cardiovascular parameters in pregnant women. Methods Seventeen healthy pregnant women with 88% self-identifying as Hispanic were consented to participate in the longitudinal observation study. Their average age was 27.8 years (SD=4.48). A validated Oura ring was used to daily monitor objective sleep and cardiovascular parameters across the pregnancy, including resting heart rate (HR), heart rate variability (HRV) indicated by RMSSD (root mean square of successive differences) of interbeat intervals, deep, light, and Rapid EYE Movement (REM) sleep, awake time and sleep onset latency. Mixed effects models were conducted to analyze daily changing patterns of these parameters using R-4.2.0 for Mac. Results Over the pregnancy, when deep and light sleep increased by 1 hour, heart rate decreased by 5.55 bpm (p< 0.001) and 1.32 bpm (p = 0.01), respectively; when REM sleep increased by 1 hour, heart rate increased by 2.15 bpm (p =0.049). Conversely, when deep and light sleep increased by 1 hour, RMSSD increased by 10.32 ms (p< 0.001) and 2.93 ms (p< 0.02), respectively; when REM sleep increased by 1 hour, RMSSD decreased by 7.27 ms (p=0.001). There were no significant associations between HR/RMSSD and awake time/sleep onset latency. Conclusion This study appears to be the first to investigate the longitudinal relationship between sleep and cardiovascular parameters among primarily Hispanic pregnant women in the U.S. in a non-lab setting. Our study provides preliminary evidence that longer deep/light sleep and shorter REM sleep may improve cardiovascular health among pregnant women. Support (if any) National Science Foundation grants including the Smart and Connected Communities (CNS: 1831918) and Collaborative Research: Integrative Heterogeneous Learning for Intensive Complex Longitudinal Data (DMS: 2210640).

Respiration and rapid eye movement (REM) sleep substructure: short versus long episodes.

Rapid eye movement (REM) sleep in rodents is defined by the presence of theta rhythm in the absence of movement. The amplitude and frequency of theta oscillations have been used to distinguish between tonic and phasic REM sleep. However, tonic REM sleep has not been further subdivided, although characteristics of network oscillations such as cross-frequency coupling between theta and gamma vary within this sub-state. Recently, it has been shown that theta-gamma coupling depends on an optimal breathing rate of ~5 Hz. The frequency of breathing varies strongly throughout REM sleep, and the duration of single REM sleep episodes ranges from several seconds to minutes, whereby short episodes predominate. Here we studied the relation between breathing frequency, accelerometer activity, and the length of REM sleep periods. We found that small movements detected with three-dimensional accelerometry positively correlate with breathing rate. Interestingly, breathing is slow in short REM sleep episodes, while faster respiration regimes exclusively occur after a certain delay in longer REM sleep episodes. Thus, merging REM sleep episodes of different lengths will result in a predominance of slow respiration due to the higher occurrence of short REM sleep periods. Moreover, our results reveal that not only do phasic REM sleep epochs predominantly occur during long REM sleep episodes, but that the long episodes also have faster theta and higher gamma activity. These observations suggest that REM sleep can be further divided from a physiological point of view depending on its duration. Higher levels of arousal during REM sleep, indicated by higher breathing rates, can only be captured in long REM sleep episodes.

Shorter rapid eye movement sleep duration in children with attention-deficit /hyperactivity disorder: the impact on quality of life

ObjectivesThe relationship of sleep with attention deficit hyperactivity disorder (ADHD) remains complex and unclear. The current study aimed to compare the subjective and objective sleep parameters among children with and without ADHD. Moreover, to address the effect of sleep parameters on the quality of life (QoL). MethodsWe assessed 42 participants who were children with ADHD (aged 6–12 years), with predominant combined presentation (23), compared to 42 healthy children, who underwent a sleep study assessment subjectively (the Children's Sleep Habits Questionnaire), and objectively (one-night Polysomnographic recording). Also, parents completed the pediatric quality of life inventory (PedsQL-P). ResultsChildren with ADHD had more subjective sleep problems. ADHD patients also had a significant decrease in total sleep time and sleep efficiency, spending more time in wake and N1 sleep stages. Moreover, they had significantly lower rapid eye movement (REM)sleep duration and less duration of deep sleep stages. Multivariate regression analysis showed that REM sleep duration was the most contributing and predictive factor to QoL and school function impairment. ConclusionChildren with ADHD have a significantly lower sleep quantity and poor sleep quality. In addition, short REM sleep duration independently contributes to further deterioration in different areas of QoL.

Association of Depressive Symptoms with Sleep Disturbance: A Co-twin Control Study.

Few studies have comprehensively evaluated the association of depression with sleep disturbance using a controlled twin study design. To cross-sectionally evaluate the association of depression with both objective and subjective sleep disturbance. We studied 246 members of the Vietnam Era Twin Registry. We measured depressive symptoms using the Beck Depression Inventory-II (BDI) and assessed major depression using structured clinical interviews. Twins underwent one-night polysomnography and 7-day actigraphy to derive measures of objective sleep and completed the Pittsburgh Sleep Quality Index for subjective sleep. Multivariable mixed-effects models were used to examine the association. Twins were all male, mostly white (97%), with a mean (SD) age of 68 (2). The mean (SD) BDI was 5.9 (6.3), and 49 (20%) met the criteria for major depression. For polysomnography, each 5-unit higher BDI, within-pair, was significantly associated with 19.7 min longer rapid eye movement (REM) sleep latency, and 1.1% shorter REM sleep after multivariable adjustment. BDI was not associated with sleep architecture or sleep-disordered breathing. For actigraphy, a higher BDI, within-pair, was significantly associated with lower sleep efficiency, more fragmentation and higher variability in sleep duration. BDI was associated with almost all dimensions of self-reported sleep disturbance. Results did not differ by zygosity, and remained consistent using major depression instead of BDI and were independent of the presence of comorbid posttraumatic stress disorder and antidepressant use. Depression is associated with REM sleep disruption in lab and sleep fragmentation and sleep variability at home, but not with sleep architecture or sleep-disordered breathing.

EEG coherence and power spectra during REM sleep related to melatonin intake in mild-to-moderate Alzheimer’s disease: a pilot study

Introduction: It has been reported that melatonin diminishes rapid eye movement (REM) sleep latency in patients with Alzheimer’s disease (AD). Pharmacological studies suggest that melatonin promotes prompt sleep installation through interaction with GABA receptors, and that it is associated with acute suppression of neural electrical activity. Nevertheless, melatonin’s effects on electroencephalographic (EEG) activity related to REM sleep onset in AD patients have not been analyzed. Thus, in this pilot study we analyzed the effects of melatonin on EEG activity during the first episode of REM sleep in eight patients treated with 5-mg of fast-release melatonin. Methods: During a single-blind, placebo-controlled study, polysomnographic recordings were obtained from frontal, central, temporal, and occipital scalp derivations. REM sleep latency, as well as the relative power (RP) and EEG coherences of six EEG bands, were compared between the placebo and melatonin conditions. Results: Results showed that melatonin intake in AD patients decreased REM sleep onset, and that this was associated with lower RP and coherence of the β and γ EEG bands. Discussion: The possibility that the inhibitory GABAergic pathways related to REM sleep generation are well-preserved in mild-to-moderate AD is discussed. We conclude that the short REM sleep onset related to melatonin intake in AD patients is associated with a significant decrease in both RP and EEG coherence, mainly in the fast frequencies.

How do people with drug-resistant mesial temporal lobe epilepsy sleep? A clinical and video-EEG with EOG and submental EMG for sleep staging study.

This study aimed to assess subjective and objective sleep parameters in a homogeneous group of drug-resistant mesial temporal lobe epilepsy (MTLE)1 patients through internationally validated clinical questionnaires, video-electroencephalographic (VEEG)2 and polysomnographic (PSG)3 studies. Fifty-six patients with definite diagnosis of MTLE who were candidates for epilepsy surgery underwent a detailed clinical history, the Pittsburgh Sleep Quality Index (PSQI),4 Epworth Sleepiness Scale (ESS),5 Stanford Sleepiness Scale (SSS),6 neurological examination, 1.5 T brain magnetic resonance imaging, VEEG and PSG. Sixteen percent of patients reported significant daytime sleepiness as measured by ESS and 27% reported low levels of sleep quality as measured by PSQI. Patients with medically resistant epilepsy by MTLE showed increased wakefulness after sleep onset (WASO) with mean ± standard deviation of 17.4 ± 15.6, longer non-rapid eye movement (NREM)7 1 (7.5 ± 4.6%) and NREM3 sleep (26.6 ± 11.8%), abnormal rapid eye movement (REM)8 latency in 30/56 patients, shorter REM sleep (16.7 ± 6.6%), and abnormal alpha delta patterns were observed in 41/56 patients. The analysis of interictal epileptic discharges (IEDs)9 evidenced highest spiking rate during NREM3 sleep and higher concordance with imaging data when IEDs were recorded in sleep, mainly during REM sleep. We concluded that patients with MTLE showed disrupted sleep architecture that may result in daytime dysfunction and sleep complaints. Furthermore, NREM sleep activated focal IEDs and them - when recorded during sleep - had higher localizing value.

Perceived poor sleep quality in the absence of polysomnographic sleep disturbance in women with severe premenstrual syndrome

Women with severe premenstrual syndrome report sleep-related complaints in the late-luteal phase, but few studies have characterized sleep disturbances prospectively. This study evaluated sleep quality subjectively and objectively using polysomnographic and quantitative electroencephalographic measures in women with severe premenstrual syndrome. Eighteen women with severe premenstrual syndrome (30.5 ± 7.6 years) and 18 women with minimal symptoms (controls, 29.2 ± 7.3 years) had polysomnographic recordings on one night in each of the follicular and late-luteal phases of the menstrual cycle. Women with premenstrual syndrome reported poorer subjective sleep quality when symptomatic in the late-luteal phase compared with the follicular phase (P < 0.05). However, there were no corresponding changes in objective sleep quality. Women with premenstrual syndrome had more slow-wave sleep and slow-wave activity than controls at both menstrual phases (P < 0.05). They also had higher trait-anxiety, depression, fatigue and perceived stress levels than controls at both phases (P < 0.05) and mood worsened in the late-luteal phase. Both groups showed similar menstrual-phase effects on sleep, with increased spindle frequency activity and shorter rapid eye movement sleep episodes in the late-luteal phase. In women with premenstrual syndrome, a poorer subjective sleep quality correlated with higher anxiety (r = -0.64, P = 0.005) and more perceived nighttime awakenings (r = -0.50, P = 0.03). Our findings show that women with premenstrual syndrome perceive their sleep quality to be poorer in the absence of polysomnographically defined poor sleep. Anxiety has a strong impact on sleep quality ratings, suggesting that better control of mood symptoms in women with severe premenstrual syndrome may lead to better subjective sleep quality.

Rapid Eye Movement Sleep in Relation to Overweight in Children and Adolescents

Short sleep duration is associated with obesity, but few studies have examined the relationship between obesity and specific physiological stages of sleep. To examine specific sleep stages, including rapid eye movement (REM) sleep and stages 1 through 4 of non-REM sleep, in relation to overweight in children and adolescents. A total of 335 children and adolescents (55.2% male; aged 7-17 years) underwent 3 consecutive nights of standard polysomnography and weight and height assessments as part of a study on the development of internalizing disorders (depression and anxiety). Body mass index (calculated as weight in kilograms divided by height in meters squared) z score and weight status (normal, at risk for overweight, overweight) according to the body mass index percentile for age and sex. The body mass index z score was significantly related to total sleep time (beta = -0.174), sleep efficiency (beta = -0.027), and REM density (beta = -0.256). Compared with normal-weight children, overweight children slept about 22 minutes less and had lower sleep efficiency, shorter REM sleep, lower REM activity and density, and longer latency to the first REM period. After adjustment for demographics, pubertal status, and psychiatric diagnosis, 1 hour less of total sleep was associated with approximately 2-fold increased odds of overweight (odds ratio = 1.85), 1 hour less of REM sleep was associated with about 3-fold increased odds (odds ratio = 2.91), and REM density and activity below the median increased the odds of overweight by 2-fold (odds ratio = 2.18) and 3-fold (odds ratio = 3.32), respectively. Our results confirm previous epidemiological observations that short sleep time is associated with overweight in children and adolescents. A core aspect of the association between short sleep duration and overweight may be attributed to reduced REM sleep. Further studies are needed to investigate possible mechanisms underpinning the association between diminished REM sleep and endocrine and metabolic changes that may contribute to obesity.

Kv3 potassium channels control the duration of different arousal states by distinct stochastic and clock‐like mechanisms

Sleep-wake behavior is tightly controlled in many animal species, suggesting genetically encoded, homeostatic control mechanisms that determine arousal-state dynamics. We reported that two voltage-gated potassium channels, Kv3.1 and Kv3.3, control sleep in wild-type and Kv3-mutant mice. Compared with wild-type (WT), homozygous double mutants (DKO) that lack these channels sleep 40% less in the light and 22% less in the dark. To understand how the lack of these channels affects sleep, we analysed arousal-state changes during the light period where the differences are greatest between WT and DKO. We determined the kinetic complexity of each arousal state from the episode durations of wakefulness, slow-wave sleep and rapid eye movement sleep (REMS). Based on the number of exponential components in episode-duration histograms, WT and DKO mice have several kinetically distinct states of wakefulness, and these states are longer in duration in DKO. For slow-wave sleep, WT mice have a single slow-wave sleep (SWS) state in contrast to DKO mice, which show two distinct SWS states, one that is 60% shorter than that in WT and a second that is similar in duration. Both WT and DKO mice have two kinetically distinct REMS states. DKO mice show an 84% reduction in the frequency of short REMS episodes (<45 s) without any change in the occurrence of long REMS episodes (>60 s). In contrast to the stochastic control of episode durations of wakefulness and SWS, the durations of both REMS states are normally distributed, indicating that the underlying control processes are fundamentally different.

A two-state stochastic model of REM sleep architecture in the rat.

Rapid eye movement (REM) sleep is a recurring state throughout the sleeping period. Based on the examination of 45 sleep records of 3-mo-old male rats during the middle of the light phase, a stochastic model is proposed for the sequence X(1),Y(2), X(2),Y(2),. of REM sleep durations X and inter-REM sleep waiting times Y experienced by a rat during a sleeping period. In our model the probability distribution of any variable in the sequence, given the past, is allowed to depend on only the immediately previous variable. The conditional distributions f(y(i) | x(i)) and g(x(i+1) | y(i)) do not depend on the index i. It is shown that the marginal distributions tend to stationarity. Aggregations of the data on a discrete time scale suggest that the conditional distributions be formulated as two-component mixtures. These component distributions are modeled as Poisson and their means are called the means of short and long waiting time and the means of short and long REM sleep duration. Associated with each mean is a probability weight. Parametric forms are given to the means and probability weights. The model estimated by maximum likelihood shows a good fit to data of the 3-mo-old rats. The model fit to a smaller data set obtained from rats aged 15-22 mo shows a significant shortening of the means for both short and long REM sleep bout durations compared with the means of the 3-mo-old rats. Neuronal correlates for the behavior of the model are discussed in the context of the reciprocal interaction model of REM sleep regulation.

Polysomnographic and Subjective Sleep Predictors of Alcoholic Relapse

Previous studies indicate that subjectively reported and objectively measured sleep abnormalities at baseline can increase the risk of relapse in treated alcoholics. However, previous studies did not include both subjective and objective sleep measures in the same group of patients. We utilized polysomnography and the Sleep Disorders Questionnaire to determine if baseline polysomnography increased the ability to predict relapse beyond the prediction with subjective measures alone, after controlling for nonsleep variables that were associated with relapse. We followed 74 patients with a DSM-III-R diagnosis of alcohol dependence, of whom 36 relapsed to at least some drinking during an average follow-up interval of 5 months. Univariate analyses revealed that relapsed patients did not differ from abstinent patients at baseline in demographics or psychiatric co-morbidity, but they had more prior treatment episodes for alcoholism, more difficulty falling asleep, more complaints of abnormal sleep, and, on polysomnography, longer sleep latencies, shorter rapid eye movement sleep latencies, and less stage 4 sleep percentage than abstinent patients. With a series of logistic regression analyses, which controlled for age and gender, we demonstrated that sleep measures improved the prediction model compared with nonsleep variables alone, and that polysomnography-measured sleep latency was the most significant predictor variable. We conclude that subjective and objective measures of baseline sleep are predictors of relapse in treated alcoholic patients. These data also suggest that neurophysiological dysfunction contributes strongly to the etiology of relapse. Finally, sleep disturbance warrants clinical attention as a target of alcoholism treatment.

Critical analysis of the theories advanced to explain short REM sleep latencies and other sleep anomalies in several psychiatric conditions

One of the most consistent and most studied sleep modifications in several psychiatric conditions is the shortening of the rapid eye movement (REM) sleep latency. While its clinical usefulness is still to be proven and its meaning relatively obscure, the appearance of a short REM latency continues to be a daily fact in sleep laboratories. Many theories compete to explain what is observed, the most important being the circadian rhythm hypotheses, the homeostatic model and the reciprocal interaction model. These three are summarised and their pros and cons are exposed in a systematic manner. Points of conflict, possible convergences and limitations are discussed in the light of recent developments on the general theories of sleep regulation.

24-hour profiles of adrenocorticotropin, cortisol, and growth hormone in major depressive illness: effect of antidepressant treatment.

Plasma ACTH, cortisol, and GH concentrations were measured at 15-min intervals for 24 h in 11 men suffering from major depressive illness during an acute episode of depression and during clinical remission following antidepressant treatment with either electroconvulsive therapy or amitriptyline. Seven age-matched normal men also were studied. During the acute phase of the illness, the patients had abnormally short rapid eye movement sleep latencies, hypercortisolism, early timing of the nadirs of the ACTH-cortisol rhythms, and shorter nocturnal periods of quiescent cortisol secretion. GH was hypersecreted during wakefulness, and a major pulse occurred before, rather than after, sleep onset. After treatment, rapid eye movement sleep latencies were lengthened, and cortisol levels returned to normal due to a decrease in the magnitude of episodic pulses. Moreover, the timing of the circadian rhythms of ACTH and cortisol as well as the duration of the quiescent period of cortisol secretion were normalized. The amount of GH secreted during wakefulness decreased to normal values, with fewer significant GH pulses. The major elevation of GH secretion in the early part of the night occurred later than that during the depressive episode. These results demonstrate that a disorder of circadian rhythmicity characterizes acute episodes of major depressive illness and that this chronobiological abnormality as well as the hypersecretion of ACTH, cortisol, and GH are state rather than trait dependent.