Rapid Eye Movement Sleep Abnormalities Research Articles

Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy

Narcolepsy is a sleep disorder caused by deficiency of orexin signaling. However, the neural mechanisms by which deficient orexin signaling causes the abnormal rapid eye movement (REM) sleep characteristics of narcolepsy, such as cataplexy and frequent transitions to REM states, are not fully understood. Here, we determined the activity dynamics of orexin neurons during sleep that suppress the abnormal REM sleep architecture of narcolepsy. Orexin neurons were highly active during wakefulness, showed intermittent synchronous activity during non-REM (NREM) sleep, were quiescent prior to the transition from NREM to REM sleep, and a small subpopulation of these cells was active during REM sleep. Orexin neurons that lacked orexin peptides were less active during REM sleep and were mostly silent during cataplexy. Optogenetic inhibition of orexin neurons established that the activity dynamics of these cells during NREM sleep regulate NREM-REM sleep transitions. Inhibition of orexin neurons during REM sleep increased subsequent REM sleep in "orexin intact" mice and subsequent cataplexy in mice lacking orexin peptides, indicating that the activity of a subpopulation of orexin neurons during the preceding REM sleep suppresses subsequent REM sleep and cataplexy. Thus, these results identify how deficient orexin signaling during sleep results in the abnormal REM sleep architecture characteristic of narcolepsy.

Vivid dreams are associated with a high percentage of REM sleep: a prospective study in veterans.

Vivid dreams are dreams that feel real or are associated with dream enactment behavior. They are prevalent in veterans, especially in those with psychiatric disorders such as post-traumatic stress disorders. Such psychiatric disorders have known association with abnormalities in rapid eye movement (REM) sleep. Vivid dreams are also described in neurological conditions, such Lewy body dementias, which are also associated with REM sleep abnormality. Although vivid dreams occur in neuropsychiatric disorders that have REM sleep abnormalities, there are no studies that have directly investigated an association between vivid dreams and REM sleep. We sought to study vivid dreams and REM sleep in veterans. Veterans undergoing polysomnography at our hospital were invited to enroll. Participants completed a dream-related questionnaire the morning after their polysomnography. We prospectively enrolled 505 veterans. After a night in the sleep laboratory, 196 of 504 (39%) reported experiencing a dream, and, of those, 117 of 190 (62%) described their dream as vivid. Discrepancies in patient totals are secondary to missing questionnaire data. Our novel finding is that participants with a high percentage of REM sleep (above 25%) were more than twice likely to report a vivid dream than participants with a lower percentage of REM sleep (P < .0001). Nonvivid dreams were not associated with a high percentage of REM sleep. Vivid dreams are associated with a high percentage of REM sleep. Further research into the role of REM sleep abnormalities in vivid dreams may help to advance understanding of neuropsychiatric disorders. Fattal D, Platti N, Hester S, Wendt L. Vivid dreams are associated with a high percentage of REM sleep: a prospective study in veterans. J Clin Sleep Med. 2023;19(9):1661-1668.

Rapid eye movement sleep in adolescent females with borderline personality disorder

Objective: The aim of the study was detecting Rapid Eye Movement (REM) sleep abnormalities in adolescent females with borderline personality disorder (BPD). Method: A case control study included a convenient sample of 30 adolescent females with BPD compared to 30 matched healthy controls. Pittsburgh Sleep Quality Index and an overnight sleep lab polysomnographic study were applied to both groups to assess sleep. Results: Patients with BPD were subjectively dissatisfied with the quality of sleep compared to controls (p&lt;0.001). Abnormalities in REM sleep in patients when compared to controls were higher REM percent (p=0.001), shorter REM latency (p=0.001), higher REM density (p=0.001) and higher number of REM periods in the first half of the night (p=0.000). Conclusion: REM sleep abnormalities are found in adolescent patients with BPD, which may be considered as trait markers for BPD.

Relevance of sleep and associated structural changes in GBA1 mouse to human rapid eye movement behavior disorder

Rapid eye movement (REM) sleep behaviour disorder (RBD) is a REM parasomnia that often predicts the later occurrence of alpha-synucleinopathies. Variants in the gene encoding for the lysosomal enzyme glucocerebrosidase, GBA, strongly increase the risk of RBD. In a GBA1-mouse model recently shown to mimic prodromal stages of α-synucleinopathy, we now demonstrate striking REM and NREM electroencephalographic sleep abnormalities accompanied by distinct structural changes in the more widespread sleep neurocircuitry.

Abnormal rapid eye movement sleep atonia control in chronic post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) and rapid eye movement (REM) sleep behavior disorder (RBD) share some common features including prominent nightmares and sleep disturbances. We aimed to comparatively analyze REM sleep without atonia (RSWA) between patients with chronic PTSD with and without dream enactment behavior (DEB), isolated RBD (iRBD), and controls. In this retrospective study, we comparatively analyzed 18 PTSD with DEB (PTSD+DEB), 18 PTSD without DEB, 15 iRBD, and 51 controls matched for age and sex. We reviewed medical records to determine PTSD clinical features and quantitatively analyzed RSWA. We used nonparametric analyses to compare clinical and polysomnographic features. PTSD patients, both with and without DEB, had significantly higher RSWA than controls (all p < .025, excepting submentalis phasic duration in PTSD+DEB). Most RSWA measures were also higher in PTSD+DEB than in PTSD without DEB patients (all p < .025). PTSD patients have higher RSWA than controls, whether DEB is present or not, indicating that REM sleep atonia control is abnormal in chronic PTSD. Further prospective studies are needed to determine whether neurodegenerative risk and disease markers similar to RBD might occur in PTSD patients.

A high-density electroencephalography study reveals abnormal sleep homeostasis in patients with rapid eye movement sleep behavior disorder

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by disrupting motor enactments during REM sleep, but also cognitive impairments across several domains. In addition to REM sleep abnormalities, we hypothesized that RBD patients may also display EEG abnormalities during NREM sleep. We collected all-night recordings with 256-channel high-density EEG in nine RBD patients, predominantly early-onset medicated individuals, nine sex- and age- matched healthy controls, and nine additional controls with matched medications and comorbidities. Power spectra in delta to gamma frequency bands were compared during both REM and NREM sleep, between phasic and tonic REM sleep, and between the first versus last cycle of NREM sleep. Controls, but not RBD patients, displayed a decrease in beta power during phasic compared to tonic REM sleep. Compared to controls, RBD patients displayed a reduced decline in SWA from early to late NREM sleep. Overnight changes in the distribution of the amplitude of slow waves were also reduced in RBD patients. Without suppression of beta rhythms during phasic REM sleep, RBD patients might demonstrate heightened cortical arousal, favoring the emergence of behavioral episodes. A blunted difference between REM sleep sub-stages may constitute a sensitive biomarker for RBD. Moreover, reduced overnight decline in SWA suggests a reduced capacity for synaptic plasticity in RBD patients, which may favor progression towards neurodegenerative diseases.

Sleep, insomnia, and depression.

Since ancient times it is known that melancholia and sleep disturbances co-occur. The introduction of polysomnography into psychiatric research confirmed a disturbance of sleep continuity in patients with depression, revealing not only a decrease in Slow Wave Sleep, but also a disinhibition of REM (rapid eye movement) sleep, demonstrated as a shortening of REM latency, an increase of REM density, as well as total REM sleep time. Initial hopes that these abnormalities of REM sleep may serve as differential-diagnostic markers for subtypes of depression were not fulfilled. Almost all antidepressant agents suppress REM sleep and a time-and-dose-response relationship between total REM sleep suppression and therapeutic response to treatment seemed apparent. The so-called Cholinergic REM Induction Test revealed that REM sleep abnormalities can be mimicked by administration of cholinomimetic agents. Another important research avenue is the study of chrono-medical timing of sleep deprivation and light exposure for their positive effects on mood in depression. Present day research takes the view on insomnia, i.e., prolonged sleep latency, problems to maintain sleep, and early morning awakening, as a transdiagnostic symptom for many mental disorders, being most closely related to depression. Studying insomnia from different angles as a transdiagnostic phenotype has opened many new perspectives for research into mechanisms but also for clinical practice. Thus, the question is: can the early and adequate treatment of insomnia prevent depression? This article will link current understanding about sleep regulatory mechanisms with knowledge about changes in physiology due to depression. The review aims to draw the attention to current and future strategies in research and clinical practice to the benefits of sleep and depression therapeutics.

Sleep patterns deteriorate over time in chronic corticosterone-treated rats

Repeated corticosterone (CORT) injections reliably produce depressive-like behavior in rodents. Our previous study showed that sleep parameters were altered in rats after daily injections of CORT for 7 days, and sleep disturbances appeared to be correlated with depressive-like behavior. The aim of the present study was to investigate time-dependent correlations between changes in sleep parameters and the formation of depressive-like behavior in rats after more prolonged treatment with CORT. Rats received daily injections of CORT (40 mg/kg, s.c.) for 7, 14, or 21 days. Electroencephalographic recordings were performed to study sleep parameters. The sucrose preference test and forced swim test were performed to evaluate depressive-like behavior. Western blot was used to detect protein levels. Our results showed that 7-day CORT treatment resulted in no significant depressive-like behavior or changes in rapid-eye-movement (REM) sleep. However, the duration of non-REM sleep significantly decreased, tyrosine hydroxylase (TH) levels significantly increased, and glucocorticoid receptor (GR) expression decreased in the locus coeruleus. Treatment with CORT for 14 and 21 days increased depressive-like behavior, enhanced REM sleep, shortened REM sleep latency, decreased TH and GR levels, and increased the levels of the chaperone FK506 binding protein 51 (FKBP51) in the locus coeruleus. These results indicate that the development of depression after chronic CORT treatment may be related to the formation of sleep disorders. Abnormalities of REM sleep may be a characteristic of sleep in models of depression that is induced by chronic CORT administration in rats. The noradrenergic system and GR pathway in the locus coeruleus may be involved in the formation of depression concomitant with sleep disturbances.

Differences in rapid eye movement (REM) sleep abnormalities between posttraumatic stress disorder (PTSD) and major depressive disorder patients: REM interruption correlated with nightmare complaints in PTSD

ObjectiveThe presence of repeated nightmares in posttraumatic stress disorder (PTSD) has been hypothesized as a dysfunction of rapid eye movement (REM) sleep, but there has been remarkably little agreement about the pathophysiology. This presents a deterrent to more effective treatments. REM sleep abnormalities including elevated REM density also have been replicated in major depressive disorder (MDD). The purpose of this study was to clarify the difference of REM sleep abnormalities between the two disorders for understanding the pathophysiology of sleep disturbances in PTSD. MethodsPolysomnographic measures were compared among 14 PTSD patients (aged 23.7 ± 5.5 years) and 14 MDD patients (aged 27.9 ± 10.1 years) under drug-naive or drug-free conditions. We defined REM interruption by summing the intrusive wake times during the REM period and adding the subsequent wake times to the last epoch of REM period. The significant polysomnographic measures were correlated with PTSD symptoms within the PTSD group. ResultsREM interruption was significantly increased in the PTSD group compared with the MDD group (12.2 vs 2.1 min, p = 0.001). REM density was also significantly increased in the PTSD group compared with the MDD group (30.5 vs 23.1%, p = 0.019). Within the PTSD group, we found significant correlations between the severity of trauma-related nightmare complaints and the percentage of REM interruption (R = 0.62, p = 0.017), but not REM density. ConclusionsREM sleep abnormalities are different between PTSD and MDD. Increased REM interruption may be a biological marker correlated with nightmare complaints in PTSD patients. Treatments including pharmacotherapy that reduces REM interruption might ameliorate nightmares in PTSD.

Erratum to: Chronic Paroxetine Treatment Prevents the Emergence of Abnormal Electroencephalogram Oscillations in Huntington's Disease Mice.

Disturbance of rapid eye movement (REM) sleep appears early in both patients with Huntington’s disease (HD) and mouse models of HD. Selective serotonin reuptake inhibitors are widely prescribed for patients with HD, and are also known to suppress REM sleep in healthy subjects. To test whether selective serotonin reuptake inhibitors can correct abnormal REM sleep and sleep-dependent brain oscillations in HD mice, we treated wild-type and symptomatic R6/2 mice acutely with vehicle and paroxetine (5, 10, and 20 mg/kg). In addition, we treated a group of R6/2 mice chronically with vehicle or paroxetine (20 mg/kg/day) for 8 weeks, with treatment starting before the onset of overt motor symptoms. During and after treatment, we recorded electroencephalogram/electromyogram from the mice. We found that both acute and chronic paroxetine treatment normalized REM sleep in R6/2 mice. However, only chronic paroxetine treatment prevented the emergence of abnormal low-gamma (25–45 Hz) electroencephalogram oscillations in R6/2 mice, an effect that persisted for at least 2 weeks after treatment stopped. Chronic paroxetine treatment also normalized REM sleep theta rhythm in R6/2 mice, but, interestingly, this effect was restricted to the treatment period. By contrast, acute paroxetine treatment slowed REM sleep theta rhythm in WT mice but had no effect on abnormal theta or low-gamma oscillations in R6/2 mice. Our data show that paroxetine treatment, when initiated before the onset of symptoms, corrects both REM sleep disturbances and abnormal brain oscillations, suggesting a possible mechanistic link between early disruption of REM sleep and the subsequent abnormal brain activity in HD mice.

Chronic Paroxetine Treatment Prevents the Emergence of Abnormal Electroencephalogram Oscillations in Huntington\u2019s Disease Mice

Disturbance of rapid eye movement (REM) sleep appears early in both patients with Huntington’s disease (HD) and mouse models of HD. Selective serotonin reuptake inhibitors are widely prescribed for patients with HD, and are also known to suppress REM sleep in healthy subjects. To test whether selective serotonin reuptake inhibitors can correct abnormal REM sleep and sleep-dependent brain oscillations in HD mice, we treated wild-type and symptomatic R6/2 mice acutely with vehicle and paroxetine (5, 10, and 20 mg/kg). In addition, we treated a group of R6/2 mice chronically with vehicle or paroxetine (20 mg/kg/day) for 8 weeks, with treatment starting before the onset of overt motor symptoms. During and after treatment, we recorded electroencephalogram/electromyogram from the mice. We found that both acute and chronic paroxetine treatment normalized REM sleep in R6/2 mice. However, only chronic paroxetine treatment prevented the emergence of abnormal low-gamma (25–45 Hz) electroencephalogram oscillations in R6/2 mice, an effect that persisted for at least 2 weeks after treatment stopped. Chronic paroxetine treatment also normalized REM sleep theta rhythm in R6/2 mice, but, interestingly, this effect was restricted to the treatment period. By contrast, acute paroxetine treatment slowed REM sleep theta rhythm in WT mice but had no effect on abnormal theta or low-gamma oscillations in R6/2 mice. Our data show that paroxetine treatment, when initiated before the onset of symptoms, corrects both REM sleep disturbances and abnormal brain oscillations, suggesting a possible mechanistic link between early disruption of REM sleep and the subsequent abnormal brain activity in HD mice.

Normal Morning Melanin-Concentrating Hormone Levels and No Association with Rapid Eye Movement or Non-Rapid Eye Movement Sleep Parameters in Narcolepsy Type 1 and Type 2.

Other than hypocretin-1 (HCRT-1) deficiency in narcolepsy type 1 (NT1), the neurochemical imbalance of NT1 and narcolepsy type 2 (NT2) with normal HCRT-1 levels is largely unknown. The neuropeptide melanin-concentrating hormone (MCH) is mainly secreted during sleep and is involved in rapid eye movement (REM) and non-rapid eye movement (NREM) sleep regulation. Hypocretin neurons reciprocally interact with MCH neurons. We hypothesized that altered MCH secretion contributes to the symptoms and sleep abnormalities of narcolepsy and that this is reflected in morning cerebrospinal fluid (CSF) MCH levels, in contrast to previously reported normal evening/afternoon levels. Lumbar CSF and plasma were collected from 07:00 to 10:00 from 57 patients with narcolepsy (subtypes: 47 NT1; 10 NT2) diagnosed according to International Classification of Sleep Disorders, Third Edition (ICSD-3) and 20 healthy controls. HCRT-1 and MCH levels were quantified by radioimmunoassay and correlated with clinical symptoms, polysomnography (PSG), and Multiple Sleep Latency Test (MSLT) parameters. CSF and plasma MCH levels were not significantly different between narcolepsy patients regardless of ICSD-3 subtype, HCRT-1 levels, or compared to controls. CSF MCH and HCRT-1 levels were not significantly correlated. Multivariate regression models of CSF MCH levels, age, sex, and body mass index predicting clinical, PSG, and MSLT parameters did not reveal any significant associations to CSF MCH levels. Our study shows that MCH levels in CSF collected in the morning are normal in narcolepsy and not associated with the clinical symptoms, REM sleep abnormalities, nor number of muscle movements during REM or NREM sleep of the patients. We conclude that morning lumbar CSF MCH measurement is not an informative diagnostic marker for narcolepsy.

Rapid Eye Movement Sleep Abnormalities in Children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS).

Polysomnographic investigation of sleep architecture in children presenting with pediatric acute-onset neuropsychiatric syndrome (PANS). Fifteen consecutive subjects meeting criteria for PANS (mean age = 7.2 y; range 3-10 y) underwent single-night full polysomnography (PSG) read by a pediatric neurologist. Thirteen of 15 subjects (87%) had abnormalities detected with PSG. Twelve of 15 had evidence of rapid eye movement (REM) sleep motor disinhibition, as characterized by excessive movement, laughing, hand stereotypies, moaning, or the continuation of periodic limb movements during sleep (PLMS) into REM sleep. This study shows various forms of REM sleep motor disinhibition present in a population of children with PANS.

The Neurobiological Mechanisms and Treatments of REM Sleep Disturbances in Depression.

Most depressed patients suffer from sleep abnormalities, which are one of the critical symptoms of depression. They are robust risk factors for the initiation and development of depression. Studies about sleep electroencephalograms have shown characteristic changes in depression such as reductions in non-rapid eye movement sleep production, disruptions of sleep continuity and disinhibition of rapid eye movement (REM) sleep. REM sleep alterations include a decrease in REM sleep latency, an increase in REM sleep duration and REM sleep density with respect to depressive episodes. Emotional brain processing dependent on the normal sleep-wake regulation seems to be failed in depression, which also promotes the development of clinical depression. Also, REM sleep alterations have been considered as biomarkers of depression. The disturbances of norepinephrine and serotonin systems may contribute to REM sleep abnormalities in depression. Lastly, this review also discusses the effects of different antidepressants on REM sleep disturbances in depression.

Orexin/Hypocretin Activates mTOR Complex 1 (mTORC1) via an Erk/Akt-independent and Calcium-stimulated Lysosome v-ATPase Pathway

The lack of the neuropeptide orexin, also known as hypocretin, results in narcolepsy, a chronic sleep disorder characterized by frequent sleep/cataplexy attacks and rapid eye movement sleep abnormalities. However, the downstream pathways of orexin signaling are not clearly understood. Here, we show that orexin activates the mTOR pathway, a central regulator of cell growth and metabolism, in the mouse brain and multiple recombinant cell lines that express the G protein-coupled receptors (GPCRs), orexin 1 receptor (OX1R) or orexin 2 receptor (OX2R). This orexin/GPCR-stimulated mTOR activation is sensitive to rapamycin, an inhibitor of mTOR complex 1 (mTORC1) but is independent of two well known mTORC1 activators, Erk and Akt. Rather, our studies indicate that orexin activates mTORC1 via extracellular calcium influx and the lysosome pathway involving v-ATPase and Rag GTPases. Moreover, a cytoplasmic calcium transient is sufficient to mimic orexin/GPCR signaling to mTORC1 activation in a v-ATPase-dependent manner. Together, our studies suggest that the mTORC1 pathway functions downstream of orexin/GPCR signaling, which plays a crucial role in many physiological and metabolic processes.

New susceptibility variants to narcolepsy identified in HLA class II region.

Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, is tightly associated with human leukocyte antigen HLA-DQB1*06:02. DQB1*06:02 is common in the general population (10-30%); therefore, additional genetic factors are needed for the development of narcolepsy. In the present study, HLA-DQB1 in 664 Japanese narcoleptic subjects and 3131 Japanese control subjects was examined to determine whether HLA-DQB1 alleles located in trans of DQB1*06:02 are associated with narcolepsy. The strongest association was with DQB1*06:01 (P = 1.4 × 10(-10), odds ratio, OR = 0.39), as reported in previous studies. Additional predisposing effects of DQB1*03:02 were also found (P = 2.5 × 10(-9), OR = 1.97). A comparison between DQB1*06:02 heterozygous cases and controls revealed dominant protective effects of DQB1*06:01 and DQB1*05:01. In addition, a single-nucleotide polymorphism-based conditional analysis controlling for the effect of HLA-DQB1 was performed to determine whether there were other independent HLA associations outside of HLA-DQB1. This analysis revealed associations at HLA-DPB1 in the HLA class II region (rs3117242, P = 4.1 × 10(-5), OR = 2.45; DPB1*05:01, P = 8.1 × 10(-3), OR = 1.39). These results indicate that complex HLA class II associations contribute to the genetic predisposition to narcolepsy.

Polysomnographic picture of multiple sclerosis: Correlation with MRI findings

Very few studies have utilized polysomnogram (PSG) in studying sleep in MS patients; therefore, the objectives of the present study are to determine whether disturbance of sleep exists in patient with MS and whether they correlate with magnetic resonance imaging (MRI) findings. Twenty-two patients with MS were subjected to full clinical and neurological assessment, sleep history, an overnight and following day polysomnographic study, and MRI study. Fifteen healthy subjects were selected as a control group for polysomnographic data. MS patients had significantly reduced sleep efficiency % compared to control group (75 ± 6 versus 90 ± 2), increased in sleep latency (38 ± 24 versus 11 ± 2) and in arousal index (15 ± 6 versus 4 ± 2), decreased depth of sleep (21 ± 5 versus 23 ± 1), increased periodic leg movement (PLM) index (10 ± 7 versus 4 ± 1), increased respiratory disturbance index (5 ± 6 versus 0.4 ± 0.7), decreased rapid eye movement (REM) sleep percentages (17 ± 4 versus 23 ± 1). MRI for patients with sleep disordered breathing (SDB) showed greater plaques in the medulla, those with PLM had greater plaques in the spinal cord, and greater plaques in the pons for those with abnormal REM sleep. Sleep disturbances are pervasive in patients with MS, they may be due to; PLM, SDB, location of lesions and narcolepsy. Quality of life is affected and coping with the disease is made difficult by sleep disorders. Significant improvements in overall quality of life may be gained by an increased clinical awareness and appropriate treatment of sleep disorders.

Association analysis of the major histocompatibility complex, class II, DQ β1 gene, HLA-DQB1, with narcolepsy in Han Chinese patients from Taiwan

BackgroundNarcolepsy is a rare, chronic, disabling neuropsychiatric disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and abnormal rapid eye movement sleep. It is strongly associated with the HLA-DQB1∗06:02 allele in various ethnic groups. Our study aimed to investigate the allelic spectrum of HLA-DQB1 in a sample of Han Chinese patients with narcolepsy and control subjects from Taiwan. MethodsWe determined the genotype of the major histocompatibility complex, class II, DQ β1 gene, HLA-DQB1, in 72 narcolepsy subjects (44 men, 28 women), including 52 narcolepsy subjects with cataplexy (narcolepsy+cataplexy), 20 narcolepsy subjects without cataplexy (narcolepsy–cataplexy), and 194 control subjects (94 men, 100 women) using a sequence-specific oligonucleotide-probe hybridization technique. ResultsWe found a strong HLA-DQB1∗06:02 association in narcolepsy+cataplexy subjects (odds ratio [OR], 321.4 [95% confidence interval {CI}, 70.7–1461.4]). The association was less prominent in narcolepsy–cataplexy subjects (OR, 6.9 [95% CI, 2.4–20.1]). In addition to the DQB1∗06:02, we found that ∗03:01 also was a predisposing allele (OR, 2.0 [95% CI, 1.1–3.7]) in narcolepsy+cataplexy subjects, though the ∗06:01 was a predisposing allele (OR, 2.8 [95% CI, 1.2–6.7]) in narcolepsy–cataplexy subjects. Furthermore, we found a significant overrepresentation of DQB1∗06:02 homozygotes in narcolepsy+cataplexy subjects. ConclusionsOur data add further support to the strong association of the HLA-DQB1∗06:02 allele with narcolepsy, especially in narcolepsy+cataplexy patients. Our study also indicates additional HLA-DQB1 alleles may modify the presentation of narcolepsy+cataplexy patients, such as DQB1∗03:01 and DQB1∗06:01 in our study. Our results are limited by the small sample size and can only be considered as preliminary findings.

Acute administration of fluoxetine normalizes rapid eye movement sleep abnormality, but not depressive behaviors in olfactory bulbectomized rats

In humans, depression is associated with altered rapid eye movement (REM) sleep. However, the exact nature of the relationship between depressive behaviors and sleep abnormalities is debated. In this study, bilateral olfactory bulbectomy (OBX) was carried out to create a model of depression in rats. The sleep-wake profiles were assayed using a cutting-edge sleep bioassay system, and depressive behaviors were evaluated by open field and forced swimming tests. The monoamine content and monoamine metabolite levels in the brain were determined by a HPLC-electrochemical detection system. OBX rats exhibited a significant increase in REM sleep, especially between 15:00 and 18:00 hours during the light period. Acute treatment with fluoxetine (10 mg/kg, i.p.) immediately abolished the OBX-induced increase in REM sleep, but hyperactivity in the open field test and the time spent immobile in the forced swimming test remained unchanged. Neurochemistry studies revealed that acute administration of fluoxetine increased serotonin (5-HT) levels in the hippocampus, thalamus, and midbrain and decreased levels of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA). The ratio of 5-HIAA to 5-HT decreased in almost all regions of the brain. These results indicate that acute administration of fluoxetine can reduce the increase in REM sleep but does not change the depressive behaviors in OBX rats, suggesting that there was no causality between REM sleep abnormalities and depressive behaviors in OBX rats.

Subthalamic nucleus deep brain stimulation restores normal rapid eye movement sleep in Parkinson's disease

In Parkinson's disease, sleep disturbance is a common occurrence. We evaluated sleep in 10 patients with Parkinson's disease (age, 57.5 ± 9.8 years; disease duration, 12.3 ± 2.7 years) before and after subthalamic nucleus deep brain stimulation using the Parkinson's disease sleep scale and polysomnography. Their total sleep scale scores and daytime sleepiness subscale scores significantly improved after subthalamic nucleus-deep brain stimulation. The novel findings from this study significantly increased normal rapid eye movement sleep, and decreased abnormal rapid eye movement sleep without atonia after deep brain stimulation in patients with Parkinson's disease. The improved total sleep scale score correlated with decreased wakefulness after sleep onset. Moreover, improved daytime sleepiness correlated with increased normal rapid eye movement sleep time. Sleep improvement did not significantly correlate with resolution of motor complication or reduced dopaminergic dosages. Subthalamic nucleus-deep brain stimulation may have beneficial effects on sleep disturbance in advanced Parkinson's disease by restoring sleep architecture and normal rapid eye movement sleep.