[Prevalence of sleep-related breathing disorders of inpatients with psychiatric disorders]. / Prävalenz schlafbezogener Atmungsstörungen bei stationären Patienten mit psychischen Erkrankungen.

BACKGROUND: Sleep-related breathing disorders seriously impair well-being and increase the risk for relevant somatic and psychiatric disorders. Moreover, risk factors for sleep-related breathing disorders are highly prevalent in psychiatric patients. The aim of this study was for the first time in Germany to study the prevalence of obstructive sleep apnea syndrome (OSAS) as the most common form of sleep-related breathing disorder in patients with psychiatric disorders. METHODS: In 10 psychiatric hospitals in Germany and 1 hospital in Switzerland, a total of 249 inpatients underwent an 8­channel sleep polygraphy to investigate the prevalence of sleep apnea in this group of patients. RESULTS: With a conspicuous screening result of 23.7% of the subjects, a high prevalence of sleep-related breathing disorders was found to occur among this group of patients. Male gender, higher age and high body mass index (BMI) were identified as positive risk factors for the detection of OSAS. DISCUSSION: The high prevalence indicates that sleep apnea is a common sleep disorder among psychiatric patients. Although OSAS can lead to substantial disorders of the mental state and when untreated is accompanied by serious somatic health problems, screening procedures are not part of the routine work-up in psychiatric hospitals; therefore, sleep apnea is presumably underdiagnosed in psychiatric patients. In view of the results of this and previous studies, this topic complex should be the subject of further research studies.

Sleep after intranasal progesterone vs. zolpidem and placebo in postmenopausal women - A randomized, double-blind cross over study.

CONTEXT: The loss of progesterone during menopause is linked to sleep complaints of the affected women. Previously we demonstrated sleep promoting effects of oral progesterone replacement in postmenopausal women. The oral administration of progesterone, however, is compromised by individual differences in bioavailability and metabolism of the steroid. OBJECTIVE: We compared the sleep-endocrine effects after intranasal progesterone (MPP22), zolpidem and placebo in healthy postmenopausal women. DESIGN: This was a randomized double-blind cross-over study. SETTING: German monocentric study PARTICIPANTS: Participants were 12 healthy postmenopausal women. INTERVENTIONS: Subjects received in randomized order four treatments, 2 doses of intranasal progesterone (4.5 mg and 9 mg of MPP22), 10 mg of zolpidem and placebo. OUTCOME MEASURES: Main outcome were conventional and quantitative sleep-EEG variables. Secondary outcomes were the subjective sleep variables and the sleep related concentrations of cortisol, growth hormone (GH), melatonin and progesterone. RESULTS: Sleep promoting effects were found after the higher dosage of MPP22 and after zolpidem. Zolpidem prompted benzodiazepine-like effects on quantitative sleep EEG as expected, whereas no such changes were found after the two dosages of MP22. Nocturnal progesterone levels increased after 9.0 mg MPP22. No other changes of hormone secretion were found. CONCLUSIONS: Our study shows sleep promoting effects after intranasal progesterone. The spectral signature of intranasal progesterone did not resemble the sleep-EEG alterations induced by GABA active compounds. Progesterone levels were elevated after 9.0 mg MPP22. No other endocrine effects were observed.

Corticotropin-releasing hormone induces depression-like changes of sleep electroencephalogram in healthy women.

We reported previously that repetitive intravenous injections of corticotropin-releasing hormone (CRH) around sleep onset prompt depression-like changes in certain sleep and endocrine activity parameters (e.g. decrease of slow-wave sleep during the second half of the night, blunted growth hormone peak, elevated cortisol concentration during the first half of the night). Furthermore a sexual dimorphism of the sleep-endocrine effects of the hormones growth hormone-releasing hormone and ghrelin was observed. In the present placebo-controlled study we investigated the effect of pulsatile administration of 4×50µg CRH on sleep electroencephalogram (EEG) and nocturnal cortisol and GH concentration in young healthy women. After CRH compared to placebo, intermittent wakefulness increased during the total night and the sleep efficiency index decreased. During the first third of the night, REM sleep and stage 2 sleep increased and sleep stage 3 decreased. Cortisol concentration was elevated throughout the night and during the first and second third of the night. GH secretion remained unchanged. Our data suggest that after CRH some sleep and endocrine activity parameters show also depression-like changes in healthy women. These changes are more distinct in women than in men.

Neurology and psychiatry: waking up to opportunities of sleep. : State of the art and clinical/research priorities for the next decade.

In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.

[Hypnotics--state of the science]. / Hypnotika--Stand der Forschung.

This article provides an overview of the indications and effects of sleep-inducing drugs. Pharmacological treatment should only be considered in cases of insufficient response to non-pharmacological interventions. Benzodiazepines and benzodiazepine receptor agonists are indicated for the short-term treatment of acute insomnia. Due to the risk of tolerance and dependency, sedative antihistamines and antidepressants are widely used as long-term hypnotics. Other substances, including herbal compounds and melatonin have few side effects; however, the therapeutic efficacy is very limited. Currently, long-term data on the efficacy and tolerability of sleep-inducing substances are lacking. Specifically in cases of non-response to first line treatment, extended psychiatric and somatic evaluation and treatment of associated disorders are recommended.

[Sleep medicine differential diagnostics in psychiatry and psychotherapy]. / Schlafmedizinische Differenzialdiagnostik in Psychiatrie und Psychotherapie.

Complaints about disturbed sleep or increased daytime sleepiness are among the most frequent symptoms reported to psychiatrists by patients. Such complaints can be symptoms of an underlying psychiatric disorder or indicative of a separate or comorbid sleep disorder. Hence, basic knowledge in the differential diagnosis of sleep medicine pathologies is pivotal for psychiatrists and psychotherapists. In the present overview following a description of the diagnostic methods, the diagnostic work-up according to the major symptomatic clusters, namely disturbances in initiating and maintaining sleep, abnormal nocturnal movements and excessive daytime sleepiness will be presented.

The neural correlates and temporal sequence of the relationship between shock exposure, disturbed sleep and impaired consolidation of fear extinction.

Consolidation of extinction learning is a primary mechanism disrupted in posttraumatic stress disorder (PTSD), associated with hypoactivity of the ventromedial prefrontal cortex and hippocampus. A role for rapid eye movement (REM) sleep disturbances in this failure to consolidate extinction learning has been proposed. We performed functional magnetic resonance imaging (fMRI) with simultaneous skin conductance response (SCR) measurements in 16 healthy participants during conditioning/extinction and later recall of extinction. The visual stimuli were basic geometric forms and electrical shocks functioned as the unconditioned stimulus. Between the conditioning/extinction and recall sessions, participants received a 90-min sleep window in the sleep laboratory. This daytime sleep was polysomnographically recorded and scored by professionals blind to the study design. Only seven out of 16 participants had REM sleep; participants without REM sleep had a significantly slower decline of both SCR and neural activity of the laterodorsal tegmentum in response to electrical shocks during conditioning. At recall of fear extinction, participants with preceding REM sleep had a reduced SCR and stronger activation of the left ventromedial prefrontal cortex and bilateral lingual gyrus in response to the extinguished stimulus than participants lacking REM sleep. This study indicates that trait-like differences in shock reactivity/habituation (mediated by the brainstem) are predictive of REM sleep disruption, which in turn is associated with impaired consolidation of extinction (mediated by the ventromedial prefrontal cortex). These findings help understand the neurobiological basis and the temporal sequence of the relationship between shock exposure, disturbed sleep and impaired consolidation of extinction, as observed in PTSD.

Association of auditory hallucinations and anticonvulsant hypersensitivity syndrome with carbamazepine treatment. A case report.

Carbamazepine is effective in the treatment of acute mania and in the prevention of episodes in bipolar disorder, and it may also be useful in depression, impulse-control disorder and withdrawal from alcohol and benzodiazepine dependence. A potentially life-threatening side effect is the anticonvulsant hypersensitivity syndrome. Here, we describe a patient who developed severe auditory hallucinations followed by a distinct hypersensitivity syndrome most likely induced by carbamazepine treatment.

Brain activation and hypothalamic functional connectivity during human non-rapid eye movement sleep: an EEG/fMRI study.

Regional differences in sleep EEG dynamics indicate that sleep-related brain activity involves local brain processes with sleep stage specific activity patterns of neuronal populations. Macroscopically, it is not fully understood which cerebral brain regions are involved in the successive discontinuation of wakefulness. We simultaneously used EEG and functional MRI on 9 subjects (6 female: mean = 24.1 years, 3 male: mean = 26.0 years) and analyzed local blood oxygenation level dependent signal changes linked to the transition from wakefulness to different non-rapid eye movement (NREM) sleep stages (according to Rechtschaffen and Kales) of the first sleep cycles after 36 h of total sleep deprivation. Several brain regions throughout the cortex, the limbic lobe, the thalamus, the caudate nucleus, as well as midbrain structures, such as the mammillary body/hypothalamus, showed reduced activity during NREM sleep across all sleep stages. Additionally, we found deactivation patterns specific to NREM sleep stages compared with wakefulness suggesting that a synchronized sleeping state can be established only if these regions interact in a well-balanced way. Sleep stage 2, which is usually linked to the loss of self-conscious awareness, is associated with signal decreases comprising thalamic and hypothalamic regions, the cingulate cortex, the right insula and adjacent regions of the temporal lobe, the inferior parietal lobule and the inferior/middle frontal gyri. The hypothalamic region known to be of particular importance in the regulation of the sleep-wake cycle shows specific temporally correlated network activity with the cortex while the system is in the sleeping state, but not during wakefulness. We describe a specific pattern of decreased brain activity during sleep and suggest that this pattern must be synchronized for establishing and maintaining sleep.

Efficacy of pergolide in treatment of restless legs syndrome: the PEARLS Study.

OBJECTIVE: To evaluate the short- and long-term safety and efficacy of pergolide therapy for restless legs syndrome (RLS) in a double-blind, placebo-controlled, randomized trial (Pergolide European Australian RLS [PEARLS] study). METHODS: We randomized 100 patients with idiopathic RLS were randomized to pergolide, 0.25 to 0.75 mg, in the evening or placebo for 6 weeks (phase 1); thereafter, patients with response on the Patient Global Impression (PGI) scale continued on double-blind pergolide or placebo, and nonresponders received open-label pergolide up to 1.5 mg/d for 12 months of treatment (phase 2). Sleep efficiency (SE) and periodic limb movements during sleep (PLMS) arousal index were monitored by centrally evaluated polysomnography (PSG). The severity of RLS was assessed using the validated International RLS Scale (IRLS). RESULTS: In phase 1 (change from baseline to week 6), pergolide reduced PLMS arousal index vs placebo (mean +/- SD, -12.6 +/- 10.0 vs -3.6 +/- 15.9; p = 0.004), and SE did not improve (mean +/- SD, +11.3 +/- 11.9% vs +6.1 +/- 18.6%; p = 0.196). Pergolide improved RLS severity score (-12.2 +/- 9.9 vs -1.8 +/- 7.5 placebo; p < 0.001) and was associated with a higher PGI response (68.1% vs 15.1%; p < 0.001) and improvements in periodic limb movements (PLM) index, PGI improvement scale, Clinical Global Impression improvement, and IRLS (all p < 0.001), patient-reported SE (p = 0.019), and quality of sleep (p < 0.001). After 12 months (phase 2), double-blind pergolide maintained improvements in PLMS arousal index and PLM index. Placebo patients switched to open-label pergolide in phase 2 exhibited marked improvements in these measures that were maintained at 12 months. Pooled results from the blinded and open-label pergolide groups demonstrated improvements at 12 months in the PLMS arousal index (p = 0.028) and PLM index (p < 0.0001) compared with placebo. Nausea and headache were more frequent with pergolide than with placebo treatment. CONCLUSIONS: Pergolide substantially improves periodic limb movement measures and subjective sleep disturbance associated with restless legs syndrome. Low-dose pergolide was well tolerated and maintained its efficacy in the long term.

Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans.

The process of normal aging is accompanied by changes in sleep-related endocrine activity. During aging, an increase in cortisol at its nadir and a decrease in renin and aldosterone concentration occur. In aged subjects, more time is spent awake and slow-wave sleep is reduced: there is a loss of sleep spindles and accordingly a loss of power in the sigma frequency range. Previous studies could show a close association between sleep architecture, especially slow-wave sleep, and activity in the glutamatergic and GABAergic system. Furthermore, recent studies could show that the natural N-methyl-D-aspartate (NMDA) antagonist and GABA(A) agonist Mg(2+) seems to play a key role in the regulation of sleep and endocrine systems such as the HPA system and renin-angiotensin-aldosterone system (RAAS). Therefore, we examined the effect of Mg(2+) in 12 elderly subjects (age range 60-80 years) on the sleep electroencephalogram (EEG) and nocturnal hormone secretion. A placebo-controlled, randomised cross-over design with two treatment intervals of 20 days duration separated by 2 weeks washout was used. Mg(2+) was administered as effervescent tablets in a creeping dose of 10 mmol and 20 mmol each for 3 days followed by 30 mmol for 14 days. At the end of each interval, a sleep EEG was recorded from 11 p.m. to 7 a.m. after one accommodation night. Blood samples were taken every 30 min between 8 p.m. and 10 p.m. and every 20 min between 10 p.m. and 7 a.m. to estimate ACTH, cortisol, renin and aldosterone plasma concentrations, and every hour for arginine-vasopressin (AVP) and angiotensin 11 (ATII) plasma concentrations. Mg(2+) led to a significant increase in slow wave sleep (16.5 +/- 20.4 min vs. 10.1 +/- 15.4 min, < or =0.05), delta power (47128.7 microV(2) +21417.7 microV(2) vs. 37862.1 microV(2) +/- 23241.7 microV(2), p < or =0.05) and sigma power (1923.0 microV(2) + 1111.3 microV(2) vs. 1541.0 microV(2) + 1134.5 microV(2), p< or =0.05 ). Renin increased (3.7 +/- 2.3 ng/ml x min vs. 2.3 +/- 1.0 ng/ml x min, p < 0.05) during the total night and aldosterone (3.6 +/- 4.7 ng/ml x min vs. 1.1 +/- 0.9 ng/ml x min, p < 0.05) in the second half of the night, whereas cortisol (8.3 +/- 2.4 pg/ml x min vs. 11.8 +/- 3.8 pg/ml x min, p < 0.01) decreased significantly and AVP by trend in the first part of the night. ACTH and ATII were not altered. Our results suggest that Mg(2+) partially reverses sleep EEG and nocturnal neuroendocrine changes occurring during aging. The similarities of the effect of Mg(2+) and that of the related electrolyte Li+ furthermore supports the possible efficacy of Mg(2+) as a mood stabilizer.

Restless legs syndrome probably induced by risperidone treatment.

BACKGROUND: According to some reports, patients treated with risperidone may develop akathisia. Restless legs syndrome (RLS), which shares some clinical features with akathisia, is a distinct movement and sleep disorder that may be induced by various drugs that act on the CNS. METHODS: We studied a 31-year-old patient suffering from a schizoaffective disorder including auditory hallucinations who developed symptoms typical of the RLS during treatment with risperidone, using polysomnography to objectify sleep disturbances and associated periodic leg movements during sleep (PLMS). RESULTS: After switching from clozapine to risperidone treatment, the patient complained about dysethesias primarily of the legs, an urge to walk around, and sleep disturbances. The latter could be confirmed by polysomnography, including an abnormal PLMS index. Risperidone was switched to haloperidol. However, RLS symptoms were still present. After switching to quetiapine, RLS symptoms vanished and a second polysomnography test demonstrated better sleep quality and normal PLMS measurements. During the whole treatment period with different neuroleptics, the patient additionally received valproic acid. CONCLUSIONS: Symptoms typical of RLS may be induced by risperidone treatment and should be differentiated from akathisia. Although polysomnography is not necessary, it may be helpful confirming the diagnosis.

A new design of a polysomnography-based multi-center treatment study for the restless legs syndrome.

Periodic limb movements (PLM) cause sleep disorders and daytime symptoms and are frequently associated with restless legs syndrome (RLS). Treatment of RLS with increased PLM during sleep (PLMS) has been evaluated in studies limited in size, methodology and study length. This long-term, placebo-controlled, multi-center, study with polysomnography (PSG) recordings has been designed in order to assess efficacy and safety parameters of pergolide treatment in RLS. This novel approach for a study was created to assure consistently high quality of sleep recording and analysis. Using defined criteria, 21 sleep centers were approved for the study after a pilot phase. Seventeen centers with 16 different PSG systems randomized 100 patients. Digital sleep recordings from 4 visits (baseline, 6 weeks, 6 months, 1 year) were submitted to one central evaluation center following previously defined standardized operating procedures. Visual scoring of all recordings was performed by one independent scorer. Reliability of scoring was evaluated for 20 randomly selected baseline recordings. The mean epoch by epoch agreement for sleep stages was 88% (range 81-96%), mean arousal re-scoring differed by 0.5 (range: -16 to 20), and mean PLM index re-scoring differed by 0.1 (range: -1.5 to 2.1). Using one scorer with a demonstrated high reliability in PSG scoring for all sleep recordings was very effective in terms of study cost, study duration, and data quality.

Increased alpha activity in REM sleep in de novo patients with Parkinson's disease.

We compared the sleep structure including a quantitative electroencephalographic (EEG) analysis and the frequency of periodic limb movements (PLM) in 17 patients with Parkinson's disease (PD; 10 men, seven women, mean age 65.9 years, mean Hoehn and Yahr stage 1.8) who had never been treated with dopaminergic agents (de novo), and 10 healthy controls (six men, four women, mean age 64.5 years). The REM sleep EEG of the PD patients was characterized by a sustained increase in the high-theta/alpha (7.8-10.5 Hz) frequency range during the first one-third (i.e., 11.00 p.m. to 01.40 a.m.) of the night. There was no significant difference in the sleep continuity and sleep architecture as well as in the PLM index between both groups. The analysis of the temporal dynamics of the observed changes suggests a dysregulation of the REM sleep homeostasis in the patients with PD.

Normal IPT and IBZM SPECT in drug-naive and levodopa-treated idiopathic restless legs syndrome.

Fourteen drug-naive and 11 levodopa-treated patients with idiopathic restless legs syndrome (RLS), and 10 controls age-matched to each RLS group separately were examined with polysomnography (PSG), [(123)I]-(N)-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ((123)I-IPT) SPECT, and [(123)I]-(S)-2-hydroxy-3-iodo-6-methoxy-[(1-ethyl-2-pyrrolidinyl)methyl] benzamide ((123)I-IBZM) SPECT. Drug-naive and levodopa-treated patients with RLS and controls showed similar striatal dopamine transporter and dopamine D(2)-receptor binding, the latter declining with age. The authors conclude that striatal dopamine transporter and receptor density is normal in drug-naive and levodopa-treated patients with RLS.

Reduced NAA in the thalamus and altered membrane and glial metabolism in schizophrenic patients detected by 1H-MRS and tissue segmentation.

Functional and structural abnormalities in the thalamus as well as a generalized phospholipid membrane disorder have been implicated in the pathogenesis of schizophrenic psychosis. To determine whether thalamic neuronal abnormalities and altered membrane-associated metabolites can be detected in schizophrenic patients, we used in vivo proton magnetic resonance spectroscopy (1H-MRS) in 32 acutely-ill, medicated schizophrenic patients and 17 age-matched controls. Thalamic and white matter metabolite concentrations (myo-inositol (mI), choline-containing compounds (Cho), total creatine (Cr) and N-acetylaspartate (NAA)) were estimated and corrected for atrophy (CSF) and gray and white matter contributions (GM, WM) by use of image-based voxel segmentation. Thalamic NAA was significantly reduced in schizophrenic patients, whereas Cho and mI were significantly increased in the parietal white matter. White matter Cr was significantly elevated in patients and correlated positively with the brief psychiatric rating scores (BPRS). Regional metabolite levels were inversely associated with GM and WM content reaching significance for mI and Cr in the thalamus and Cho and NAA in the white matter. Reduced NAA in the left thalamus of schizophrenic patients confirms and extends previous spectroscopic data and agrees well with histologic and imaging findings of reduced neuronal density and volume. Elevated Cho in line with 31P-MRS studies suggests increased myelin degradation thus further supporting a generalized membrane disorder in schizophrenic patients. In addition, we demonstrate the need to correct metabolite concentrations for regional tissue composition in studies employing patients with altered brain morphology.

Effect of sleep deprivation on motor performance in patients with Parkinson's disease.

Animal research provides evidence that sleep deprivation influences the dopamine system. Knowledge about the effect of sleep deprivation on motor performance in patients with Parkinsons disease is scarce. This study examines the influence of total and partial sleep deprivation compared to normal sleep on motor state and performance in Parkinson's disease. Fifteen nondepressed patients with Parkinson's disease underwent one night of total sleep deprivation (TSD), one night of partial sleep deprivation (PSD) after 3 a.m., and one control night of normal sleep (S), performed in a random, nonconsecutive order. Over a period of 3 hours the following morning, motor evaluations (United Parkinson's Disease Rating Scale, [UPDRS] and tapping rate) were performed before and every 30 minutes after intake of the usual morning dopaminergic drug dose. All patients underwent polysomnography apart from the sleep deprivation protocol. Mean UPDRS motor scores and tapping velocities did not differ significantly after each of the schedules, but a subgroup of four patients improved their motor score after partial sleep deprivation. These data do not confirm previous findings of an overall positive influence of sleep deprivation on motor function in Parkinson's disease. However, the results indicate that different response types to sleep deprivation may exist and that a subgroup of patients could benefit from partial sleep deprivation.