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To evaluate the relation between stress-related sleep reactivity and metacognitive beliefs about sleep in subjects with insomnia disorder (93) and in a group of healthy controls (30) a set of variables, including Ford Insomnia Response to Stress Test (FIRST) and Metacognition Questionnaire-Insomnia (MCQ-I), have been used. Internal consistency of the Italian version of FIRST was studied. Univariate correlation, regression analysis, and principal component analysis were also performed. The Italian version of FIRST showed good internal consistency and discriminant validity. Sleep reactivity was higher in women (p < .05) and correlates positively in both genders with metacognitive beliefs about sleep (p < .01) in insomnia. In insomnia, metacognitive beliefs may play a key role in modulating sleep reactivity. Therapeutic strategies acting selectively on metacognition to reduce stress-related sleep reactivity in insomnia may be useful.

Study objectives Sleep after learning promotes the quantitative strengthening of new memories. Less is known about the impact of sleep on the qualitative reorganization of memory content. This study tested the hypothesis that sleep facilitates both memory strengthening and reorganization as indexed by a verbal creativity task. Methods Sixty healthy university students (30 female, 30 male, 20-30 years) were investigated in a randomized, controlled parallel-group study with three experimental groups (sleep, sleep deprivation, daytime wakefulness). At baseline, 60 items of the Compound Remote Associate (CRA) task were presented. At retest after the experimental conditions, the same items were presented again together with 20 new control items to disentangle off-line incubation from online performance effects. Results Sleep significantly strengthened formerly encoded memories in comparison to both wake conditions (improvement in speed of correctly resolved items). Offline reorganization was not enhanced following sleep, but was enhanced following sleep-deprivation in comparison to sleep and daytime wakefulness (solution time of previously incubated, newly solved items). Online performance did not differ between the groups (solution time of new control items). Conclusions The results support the notion that sleep promotes the strengthening, but not the reorganization, of newly encoded memory traces in a verbal creativity task. Future studies are needed to further determine the impact of sleep on different types of memory reorganization, such as associative thinking, creativity and emotional memory processing, and potential clinical translations, such as the augmentation of psychotherapy through sleep interventions.

Several lines of evidence suggest that brain serotonergic systems may be disturbed in obsessive compulsive disorder (OCD). The serotonergic system strongly affects sleep and characteristic abnormalities of sleep are documented in depression. This study, therefore, aimed to investigate sleep structure of OCD patients in order to evaluate whether similar changes as in depression are present. Up to now, this issue has been addressed only in few studies with small numbers of patients. Sleep patterns of 62 unmedicated patients with primary OCD and 62 age- and sex-matched healthy controls were investigated by polysomnography. Additionally, the impact of tryptophan depletion on sleep was studied in a subgroup of 12 OCD patients and 12 controls. The OCD patients exhibited moderate, but significant disturbances of sleep continuity measures but no abnormalities of slow wave sleep or REM sleep, except a significant elevation of 1st REM density. Tryptophan depletion induced a worsening of sleep continuity, but no changes of REM sleep or slow wave sleep. Assuming that changes of sleep architecture indicate underlying neurobiological abnormalities, this study indicates that neurobiological disturbances are different in primary OCD as compared with primary depression.

Attention deficit/hyperactivity disorder (ADHD) is a frequent disorder that often persists in adulthood. Persistent ADHD is known to be a serious risk factor for other disorders in adulthood, and adults with ADHD often report on sleep disorders. Despite this, only few studies have investigated the subjective and objective quality of sleep in adults suffering from ADHD. Previous studies have revealed seriously impaired subjective sleep quality and increased nocturnal motor activity in spite of essentially normal standard polysomnographic parameters in this patient group. However, primary sleep disorders such as sleep apnea syndrome or restless legs syndrome (RLS) may be misdiagnosed as ADHD. Moreover, ADHD and primary sleep disorders may occur as comorbidities. In particular, RLS was suggested to be highly associated with ADHD, indicating a probable common central nervous dopaminergic dysfunction. To date, larger studies with adequate sample sizes that compare sleep in adult patients with ADHD, healthy control groups and patients with other primary sleep disorders are still lacking.

A large body of studies demonstrates mild cognitive dysfunction in patients with Obsessive Compulsive Disorder (OCD). Few trials have investigated whether this dysfunction can be improved by treatment. Thirty unmedicated inpatients with OCD were administered a comprehensive neuropsychological test battery before and after 12 weeks of cognitive behavioral therapy (CBT). Thirty-nine carefully matched healthy controls were tested twice within the same interval. At baseline, patients exhibited significant impairments on several tests which normalized at follow-up. A significant group x time interaction was found for tests of nonverbal memory, set shifting and flexible, self guided behavior. Major responders improved significantly more than minor responders on the Rey-Osterrieth Figure immediate and delayed recall. Results suggest that cognitive dysfunction in OCD can improve in the course of treatment. We hypothesize that particularly cognitive behavioral treatment enables OCD patients to think and act in a more flexible way that helps them to develop more effective cognitive strategies.

Question of the study Sleep loss and weight gain are assumed to be positively correlated, probably mediated by a decreased leptin secretion and/or an increased production of ghrelin. The present study measured evening and nocturnal serum leptin secretion in patients with chronic primary insomnia and healthy controls.

Background: After studying the sleep of alcohol-dependent patients at the beginning and over the course of abstinence in earlier studies, our interest in the current study focused on the direct effect of 2 doses of alcohol [0.03 and 0.1% blood alcohol level (BAL)] on healthy sleep. This is the first polysomnographic study testing the impact of 2 doses of alcohol ingestion (thus reflecting “normal” social drinking and alcohol abuse) in a single-blind randomized design in healthy volunteers. The study evaluated a short-term acute drinking period for 3 and 2 days of withdrawal from alcohol not only for polysomnographic variables but also for subjective estimates of sleep quality. Methods: In a crossover design with a 1-week interval, healthy subjects received alcohol to raise their blood alcohol to either 0.03 or 0.1% BAL at bedtime for 3 consecutive nights after an alcohol-free baseline night. Objective (polysomnography) and subjective sleep (questionnaires) was recorded each night. During the following 2 days, alcohol was discontinued with simultaneous measurements of sleep to gauge withdrawal effects. Results: At a dose of alcohol leading to BAL of 0.03%, no clear effects could be detected. Following an evening BAL of 0.1%, a hypnotic-like effect (shortened sleep latency, reduced number of wake periods, decreased stage 1 sleep) occurred primarily during the first half of the night with signs of rebound effects being already present during the second half of the night (increased stage 1 sleep). At this dose, alcohol significantly increased slow-wave sleep (SWS) in the first half of the night and reduced REM density in the beginning of the night. After discontinuation of the higher alcohol dose, REM sleep amount increased. No significant withdrawal or rebound effects could be observed for parameters of sleep continuity during the 2 nights after discontinuation from alcohol at a BAL of 0.1%. Conclusions: Owing to the small sample size, the results of this study need to be interpreted with caution. Short-term moderate alcohol consumption (BAL 0.03%) did not significantly alter objective or subjective parameters of sleep. Higher doses of alcohol resulting in a BAL level of 0.10% immediately before going to bed mainly influenced sleep in the first half of the night, resembling the effects of a short-acting hypnotic drug, including a suppression of phasic aspects of REM sleep (REM density). Interestingly, analysis of the latter part of these nights indicated the immediate presence of withdrawal effects (increased light sleep). No statistically significant effects on sleep parameters were observable during the 2 nights of withdrawal from alcohol at the higher BAL. Interpreted carefully, our data indicate that negative effects on sleep occur already with short-term use of alcohol at doses of BAL of 0.10%, despite hypnotic-like effects during the first hours of sleep, especially during the latter part of the night.

Sleep disturbances, including reduced slow wave activity (SWA), are among the most consistently replicated biological alterations in major depression. According to the two-process model of sleep regulation, SWA is homoeostatically regulated as a function of prior waking time. This study aimed to further elucidate SWA regulation in major depression. All-night spectral analysis was performed before and after therapeutic sleep deprivation in N=20 patients suffering from major depression. Recovery sleep was studied at 1700 h after 34 h of waking time (n=10) and at 0200 h after 43 h of waking time (n=10) A significantly lower increase of SWA from baseline to recovery sleep was observed after 43 h versus 34 h of waking time The finding of a lower SWA increase after 43 h versus 34 h of waking time may indicate a circadian modulation of SWA and is in line with previous findings of studies investigating extended sleep durations or the relationships of SWA and circadian endocrine systems.

years; no relevant comorbidities). All participants had extensive experience with CBT-I according to evidence-based guidelines ( ≥ 6 sessions; period of time between CBT-I and inclusion in the present study: 2.2 ± 3.4 years) and continued suffering from clini-cally relevant insomnia (sleep onset latency or wake time after sleep onset: ≥30 min, ≥3 days/week). Seven participants were free of psychoactive medication; 3 had been on stable medication for ≥ 3 years. All participants were diagnosed in our sleep laboratory based on a clinical interview and standard physical examinations and provided written informed consent prior to the study. The study has been approved by the local ethics committee and has been registered in the German Clinical Trials Register prior to the enrollment of the first participant. The open pilot study comprised 2 baseline measurements [6 weeks before (T

Die Depression ist eine komplexe und heterogene Erkrankung, die mit Schwierigkeiten und Leistungsminderungen bei diversen Hirnfunktionen einhergeht. Auch zum Schlaf besteht ein komplexer und nicht vollständig verstandener Zusammenhang. So gehen Schlafstörungen oft einer Depression voraus, gehören zu den häufigsten Beschwerden in einer bestehenden Episode und bieten einen Ansatzpunkt für antidepressive Behandlungsstrategien.

Objective Restless legs syndrome (RLS) is a distressing sensorimotor disorder with a 5% to 10% prevalence in the United States and Western Europe. The nocturnal occurrence of symptoms often leads to severe sleep disturbances. RLS has been reported to be associated with depression and anxiety. The aim of the present study was to investigate the relationship between RLS symptom severity, sleep disturbances, and depressive symptoms. Method Questionnaire data from 100 consecutive patients with idiopathic RLS who had been investigated in our Sleep Disorders Unit from April 1999 to December 2004 were evaluated. Patients were untreated regarding RLS, depression, or sleep disturbances. Severity of RLS was assessed with the International RLS Study Group rating scale (IRLS). Depressive symptoms and subjective sleep quality were determined using the Beck Depression Inventory (BDI) and the Pittsburgh Sleep Quality Index (PSQI), respectively. Results IRLS scores indicated moderate-to-severe RLS symptoms in the population studied (mean +/- SD IRLS score = 23.6 +/- 6.7). The mean +/- SD BDI score was 9.3 +/- 5.6, with highest values on the "reduced sleep," "loss of energy," and "work difficulties" items, indicating predominating somatic symptoms of depression. Fourteen patients had a BDI score of 15 to 20 ("mild depression"), and 3 patients had a BDI score of 20 to 30 ("mild to moderate depression"). Overall, patients estimated their sleep quality as moderately impaired (mean +/- SD PSQI score = 10.9 +/- 3.7). Severity of RLS correlated with the impairment of subjective sleep quality (r = 0.281, p = .007) but not with self-rated depressive symptoms (r = 0.119, p = .237). Conclusion RLS patients scored high on the somatic items of the BDI, particularly on those related to sleep disturbance, but not on the other items that mostly address cognitive symptoms. Our results indicate that RLS might be associated with some features of depression but not with the full spectrum of a depressive disorder. The relationship between the 2 disorders should be investigated in further studies.

Question of the study Previous studies showed that disturbed sleep is a common and frequent complaint reported by tinnitus patients. The purpose of this small pilot study was to investigate the impact of tinnitus as a cause of secondary insomnia.

Objective Conventional analyses of sleep EEG recordings according to standard criteria indicate severe sleep disturbances in patients with restless legs syndrome (RLS). Spectral analysis of sleep EEG may be a sensitive tool to detect functional alterations of sleep mechanisms beyond the visual scoring of polysomnographic records. We analysed sleep EEG spectral power differences between RLS patients and healthy subjects. Furthermore, we studied the relationship of sleep EEG spectral power to the occurrence of periodic leg movements in sleep (PLMS) and arousal events. Methods Sleep EEGs from 20 patients with idiopathic RLS and of 20 age and sex matched healthy subjects were investigated. The spectral analysis was carried out on the same 30 s epochs for which sleep stages had been determined. As a first step, whole-night spectral power excluding epochs with an arousal or with a PLMS was compared separately for REM and NREM sleep between RLS and healthy subjects. In a second step, we evaluated the spectral effects of PLMS, PLMS with associated arousals and isolated arousals relative to epochs of sleep without such events in both groups. In this part of the analysis, we only included the epochs of sleep stage 2 (the main and most stable non-REM sleep stage) and of REM sleep. Results Spectral power of all sleep epochs (excluding arousals and PLMS) did not differ between patients with RLS and healthy subjects. As expected, arousals and PLMS-associated arousals resulted in a significant increase in higher-frequency activity (alpha, beta1, beta2 and gamma bands) in both groups. Spectral power in epochs with PLMS alone did not significantly differ from spectral power in epochs without PLMS and without arousal in any of the groups. Conclusions We found no evidence for an altered cortical activity in sleep stage 2 and REM sleep epochs in RLS patients compared to that in healthy controls if epochs with arousals were not considered. Furthermore, while PLMS associated with an arousal have a high impact on EEG spectra, the effect of a PLMS without arousal seems to be minor and transient. Significance Our data suggest that RLS related symptoms may intermittently disrupt sleep but do not appear to involve a persistent disturbance of the basic sleep generating patterns.

Clomethiazole is widely used in European countries to treat alcohol withdrawal symptoms including delirium tremens. The current study aimed to explore the effects of clomethiazole on the sleep of healthy volunteers. We postulated both a hypnotic and a REM suppressive effect as well as the occurrence of a rebound phenomenon following three days of treatment with clomethiazole. The study group was composed of five men and five women. The probands were examined in the sleep laboratory throughout a course of seven nights. The first night was considered as the adaptation night and the second as the baseline night. Prior to nights 3 to 5, probands took 384 mg clomethiazole at 22 hours. The 6th and 7th nights served to record potential effects of medication discontinuation. The current study confirms the indication in the scientific literature with regard to hypnotic and REM-suppressive effects of clomethiazole, as well as a rebound phenomenon following discontinuation of the medication. The effect of clomethiazole on the sleep EEG was most obvious in the first half of the night. The analysis of the polysomnogram in terms of each half of the night gave no indication of a rebound phenomenon during the second half. The REM sleep-suppressing component of clomethiazole is of great interest in connection with its use in treating delirium tremens. The rebound phenomenon in healthy controls after only three days of medication at a relatively low dosage of clomethiazole underscores the need to administer it in doses individually tailored to the extent of the alcohol withdrawal syndrome in the individual patient.

Question of the study As sedating antidepressants have been used increasingly in the treatment of insomnia, the question whether they elicit periodic leg movements in sleep (PLMS) and thereby disturb sleep patterns may be clinically relevant. PLMS are generally supposed to play a role in eliciting and maintaining sleep disturbances in patients with otherwise unexplained insomnia or daytime sleepiness. We evaluated the PLMS data from a double-blind, placebo-controlled polysomnographic treatment study with doxepin in patients with primary insomnia. The aim of the study was to investigate the influence of low-dose doxepin on PLMS.

Introduction Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), and trimipramine, a tricyclic antidepressant (TCA), were compared in terms of efficacy and tolerability in a six-week, parallel group, double-blind pilot study in 41 geriatric patients with major depression (61 - 85 years old). Method The Hamilton Rating Scale for Depression (HAMD-17), the Montgomery-Asberg Rating Scale (MADRS), the Adjective Mood Scale (Bf-S), the Clinical Global Impression (CGI), and the Patients Global Impression (PGI) were used to measure changes in depressive symptoms. Results Improvement with treatment was found on all scales. Efficacy and tolerability were similar in both groups. No statistically significant differences were found. Conclusion These findings suggest that fluoxetine and trimipramine are comparable in terms of efficacy and tolerability in the treatment of major depression in geriatric patients.

Background Tryptophan depletion (TD) has been shown to induce a transient mood-lowering effect in psychiatric patients and susceptible healthy subjects. We investigated the effects of TD on cortisol secretion in psychiatric patients and healthy subjects based on the hypothesis that the potential mood-lowering effects may be associated with increased activity of the hypothalamic-pituitary-adrenal axis, thus leading to a rise of cortisol secretion. Methods After TD at 18.00 h, salivary cortisol was sampled in the evening and on the following morning. The first study was a randomized, placebo-controlled, crossover study in healthy subjects. Two further open trials in patients with obsessive-compulsive disorder (OCD) and primary insomnia compared the effects of TD on cortisol with baseline conditions. Results In healthy subjects, TD significantly diminished cortisol the next morning compared with placebo. In OCD patients and primary insomniacs, cortisol the morning after TD was lowered compared with baseline. Evening cortisol was not affected by TD in any of the groups. Conclusions Contrary to expectation, TD led to a comparable decrease of morning cortisol in all groups investigated. However, these findings are consistent with former studies analyzing the impact of antiserotonergic drugs on cortisol secretion. The results underline that the antiserotonergic effects caused by TD may influence cortisol secretion.

Sleep, Depression and Insomniac Complaints It has been known for long that depressive disorders are almost always accompanied by disturbances of sleep. Neurobiologically oriented sleep research was

Sodium oxybate (γ-hydroxybutyric acid, GHB) is a neurotransmitter in the human brain which exerts sedative effects and is used therapeutically in the treatment of narcolepsy. Current safety recommendations have been formulated for the use of GHB in patients with preexisting breathing disorders. We report the case of a 39-year-old female with narcolepsy and cataplexy revealing the de novo emergence of central sleep apneas in a Cheyne-Stokes pattern under constant treatment with GHB. After discontinuation of GHB, polysomnographic re-evaluation demonstrated the disappearance of central sleep apneas. To our knowledge, this is the first report of de novo central sleep apneas induced by GHB in a patient without pre-existing sleep-disordered breathing, suggesting that there is a need for further investigation and potentially an extension of the safety guidelines to patients without a pre-existing breathing disorder.

The crucial role of a hippocampal-cortical replay that gradually strengthens hippocampus-independent cortico-cortical connections has been recently emphasized for the prefrontal cortex (PFC). In a prior analysis, we demonstrated that bi-frontal anodal tDCS significantly decreased total sleep time in healthy participants. To further elucidate the relevance of prefrontal activity levels for sleep-related memory consolidation, we explore the effects of bi-frontal tDCS on pre-post sleep memory consolidation. 18 healthy participants (13 females, age 53.1 ± 6.6 years) underwent three experimental nights with one of three counterbalanced tDCS protocols (anodal, cathodal, sham) immediately prior to polysomnography (11 pm to 7 am, interval of 3–7 d). tDCS was transferred via two pairs of electrodes (5 × 7 cm over FP1/FP2 and 10 cm x 10 cm over P3/P4) covered with electrode cream (1 mA over each target electrode, ramp up/down of 30 s, interstimulus interval 20 min). At 8 pm, 46 semantically related word-pairs were presented in a randomized order (Presentation® software) followed by repeatedly tapping a five-element sequence of numbers as fast and accurately as possible. At 8 am on the following morning, memory retrieval was assessed in a cued recall test for word-pairs (percentage of correctly retrieved referred to encoded words) and in a finger tapping test session (percentage of average speed and accuracy improvement). Bi-frontal tDCS did not result in significant changes in pre-post sleep memory consolidation in either of the examined memory systems. Specifically, repeated measures analyses of variance detected no significant condition effect for the percentage of correct word pairs ( F = 0.2, p = 0.820, pETA 2 = 0.012), finger tapping speed ( F = 1.9, p = 0.167, pETA 2 = 0.113) or accuracy ( F = 0.1, p = 0.827, pETA 2 = 0.010). In contrast to our finding of a decreased total sleep time in healthy participants following bi-frontal anodal tDCS, the stimulation protocol did not influence sleep-related memory consolidation. As mainly remote memory has been proposed to be dependent on the PFC, the test interval could have been too short to detect long-term memory effects. Besides, the results support that sleep modulating tDCS can be considered a safe and promising tool without severe adverse cognitive effects.

Question The mechanisms underlying transcranial direct current stimulation (tDCS) induced changes of cortical excitability and arousal remain to be fully characterized. In the context of our larger study on the effects of bifrontal tDCS on overnight sleep, we analyzed tDCS-modulated resting state wake EEG data for a better understanding of tDCS’s effects on cortical arousal during wakefulness. Methods We applied a standardized tDCS protocol (1 mA/electrode, 2 × 9 min cathodal, 2 × 13 min anodal, 2 × 11 min sham, with 20 min inter-stimulation interval each) prior to nighttime sleep bilaterally to the prefrontal cortex (electrodes 5 × 7 cm, FP1/FP2; return electrodes 10 × 10 cm, P3/P4 ) of 19 healthy subjects in a randomized crossover design. We conducted 5 min resting state wake EEGs prior to stimulation (T0), after the stimulation (T1) and on the following morning (T2). In a first step of analysis for EEG power differences between conditions at a single frequency, we calculated false discovery rate (FDR) corrected significances, using the Benjamini-Hochberg step-up procedure to assess the significance of the multiple tests. In a second exploratory step, we used uncorrected ANOVAs to further explore tDCS effects on EEG power spectra. Results The FDR-corrected approach did not reveal any significant condition effect. ANOVAs comparing T1 vs. T0 demonstrated a significant decrease in EEG gamma power after cathodal stimulation. A significant main effect for the factor Condition was observed for frequencies of the gamma range. ANOVAs comparing T2 vs. T0 demonstrated a significant increase in EEG gamma power after anodal stimulation and also a significant main effect for the factor Condition for frequencies of the gamma band. Conclusions Exploratory resting state EEG analyses suggested polarity-specific changes in cortical arousal as indexed by resting state EEG power in the gamma frequency range. Cortical gamma activity is considered to emerge from synchronous activity of fast-spiking inhibitory neurons in the cortex and has been linked to the integration of temporally correlated neural events as a prerequisite for attentive wakefulness. It is plausible that depolarization of cortical structures after anodal stimulation facilitates fast-spiking and EEG gamma activity, with reverse effects after cathodal stimulation.

Background and purpose: Periodic leg movements in sleep (PLMS) are a common finding in various sleep disorders. Whether PLMS are an epiphenomenon or are causally related to the presence of sleep–wake disturbances is still being debated. We investigated the relationship of the occurrence of PLMS to patients' perception of sleep quality during a night of polysomnography in various sleep disorders. Methods: The retrospective evaluation included PLMS recordings over two nights of 78 consecutive patients diagnosed with a restless legs syndrome, primary insomnia or insomnia associated with a psychiatric disorder. The subjects' perception of sleep during the polysomnography night was assessed by the subscale ‘sleep quality’ of the validated self-rating sleep questionnaire SFA (SFA-SQ). Results: SFA-SQ scores correlated with the PLMS index (number of PLMS per hour of sleep) only in patients with restless legs syndrome during the first of the two nights investigated (r=−0.464, P

This article deals with the effects of alcohol on sleep and sleep EEG of healthy individuals and alcohol-dependent patients during different phases of alcohol dependency. Healthy individuals initially experience an improvement in sleep, although a greater quantity of alcohol can lead to problems of sleep maintenance during the second half of the night. Pre-existing sleep deprivation or sleep restriction potentiates the effects of alcohol. Alcohol-dependent patients are found to be more prone to sleep problems than healthy individuals, which can facilitate the development of alcoholism. These patients experience difficulty falling asleep and suffer from a reduced total sleep time during all phases of the disorder, often accompanied by other sleep disorders such as sleep apnea syndrome or periodic leg movements during sleep. Certain predictors for the risk of relapse in abstinent alcoholics have been identified. Neurobiological findings in sleep and alcohol dependency are discussed. The cholinergic-aminergic reciprocal interaction model of REM and non-REM sleep regulation is significant in this context. Therapeutic implications are discussed.

SUMMARYHLA-DR expression on monocytes as marker for monocytic function is severely depressed after major trauma. The membrane enzyme aminopeptidase N/CD13 can trigger help in antigen processing by MHC class II molecules of antigen-presenting cells. We determined the simultaneous expression of HLA-DR and CD13 on peripheral blood monocytes of patients with major trauma (injury severity score of ≥16). 1 : 1 conjugates of phycoerythrin (PE)-to-monoclonal antibody were used in combination with QuantiBRITETM PE beads for a standardized quantification in terms of antibodies bound per cell (ABC). The very low expression of HLA-DR antigen on monocytes of patients at day 1 after major trauma confirmed previous results in the literature. Monocytic HLA-DR expression increased slowly to reach values in the lower range of healthy volunteers at day 14. Monocytic CD13 expression at day 1 showed values in the range of healthy volunteers, and a strong rise afterwards. Fourteen days after trauma, the monocytic expression of CD13 was still much higher than in the control group. Because lipopolysaccharide (LPS) and the anti-inflammatory cytokine interleukin (IL)-10 have been shown to be involved in the depressed HLA-DR expression on monocytes in trauma patients, we studied the in vitro effects of LPS and interleukin (IL)-10 on the expression of CD13 on monocytes prepared from the peripheral blood of healthy volunteers. Whereas a 3-day IL-10 treatment resulted in a down-regulation of both HLA-DR and CD13 expression on monocytes, LPS caused a down-regulation of HLA-DR but a rapid up-regulation of CD13 levels. Therefore we suggest that, with respect to monocytic CD13 expression, LPS rather than IL-10 could well be the explanation for monocytic surface molecules after severe injury, although other mediators with a CD13 regulating function have to be considered.

Objective: Disturbed sleep is typical for most depressed patients and complaints about disordered sleep are the hallmarks of the disorder. Polysomnographic sleep research has demonstrated that besides impaired sleep continuity, sleep in depression is characterized by a reduction of slow wave sleep and a disinhibition of random eye movement (REM) sleep, with a shortening of REM latency, a prolongation of the first REM period and increased REM density. Method: Our own experimental work has focused on the reciprocal interaction hypothesis of non-REM and REM sleep regulation as a model to explain the characteristic features of depressed sleep. Results: In agreement with the major tenet of this model. administration of cholinomimetics provoked shortened REM latency in healthy subjects and led to an even stronger REM sleep disinhihition in depressed patients. Manipulations of the sleep wake cycle, such as sleep deprivation or a phase advance of the sleep period, alleviate depressive symptoms. Conclusion: These data indicate a strong bidirectional relationship between sleep, sleep alterations and depression.

Over the last few years, a shift in paradigm has taken place in the diagnosis and therapy of insomnia. Traditionally, treatment focused on improving night sleep, i.e. shortening sleep latency and prolonging total sleep time. Modern approaches aim at improving or restoring the recuperative value of sleep and ensuring daytime functioning on a social, psychological and professional level. Based on the guidelines "Non-restorative Sleep" of the German Society of Sleep Research and Sleep Medicine, this article presents a clinical algorithm for the diagnosis and therapy of non-restorative sleep with predominant insomnia. The term "non-restorative sleep" permits us to view the restorative value of sleep and the resulting daytime functioning of the individual afflicted with insomnia as the focus for the diagnosis of and therapy for insomnia. This algorithm is suitable for the clinical practice of outpatient psychiatric and psychotherapeutic services as well as for psychiatric inpatients. The main features for psychiatrists and psychotherapists in the diagnosis and therapy of non-restorative sleep are underlying psychiatric-psychological factors or secondary psychiatric sequelae of chronic primary insomnias. For primary, organic and psychiatric insomnias, a broad spectrum of psychopharmacological and cognitive behavioral methods can be applied either alone or in combination.

Concerning the diagnosis and therapy of insomnia, a shift of paradigm has taken place in recent years. Traditionally, treatment has focused on improving night sleep, i. e. shortening sleep latency and prolonging total sleep time. Modern approaches aim at improving or restoring the recuperative value of sleep and ensuing daytime functioning on a social, psychological and professional level. Based on the guidelines for ‘non-restorative sleep’ of the German Society of Sleep Research and Sleep Medicine, this article presents a clinical algorithm for the diagnosis and therapy of non-restorative sleep with predominant insomnia. ‘Non-restorative sleep’ refers to the failure of sleep to be recuperative and the resulting daytime functioning impairment of the individual afflicted with insomnia.

Sleep deprivation (SD) induces a rapid amelioration of mood in about 60 % of depressed patients. After the next night of sleep, however, most patients experience a relapse. Previous studies demonstrated that a six day sleep-phase advance protocol prevents relapses in about 60 % of patients who responded positively to SD. We investigated whether also a three day phase advance of the sleep period might be able to maintain the antidepressant effects of SD. Twenty-eight medicated depressed inpatients, who had a significant improvement after a SD in one night were recruited for this study. The phase advance protocol began on the first day after SD with a bed time from 5:00 p. m. to 12:00 p. m. on the first, from 7:00 p. m. to 2:00 a. m. on the second and 9:00 p. m. to 4:00 a. m. on the third day after SD. Three patients dropped out because of protocol violations. Only ten of the remaining 25 SD responders had a relapse during the three days of phase advance treatment or during the two days after it. Two of the relapsers improved again until day 6, i. e. 68 % showed an improvement of at least 30 % six days after the beginning of the treatment. This study indicates that even a three day phase advance protocol may help to prevent relapses after successful SD.

Objective Stress-related sleep reactivity, sleep-related cognitions, and psychological factors play an important role in insomnia. The aim was to investigate their possible association in Insomnia Disorder, insomnia subgroups, and healthy subjects. Methods The cross-sectional study consisted of 93 subjects who met diagnostic criteria for Insomnia Disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) and of 30 healthy subjects. Survey instruments included the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Ford Insomnia Response to Stress Test (FIRST), Dysfunctional Beliefs about Sleep scale (DBAS), Beck Depression Inventory (BDI), and Zung Self-Rating Anxiety Scale (SAS). Descriptive statistics, Pearson correlations, χ 2 -test, and multiple linear regression were performed. Results FIRST and SAS best determined the insomnia subjects vs good sleepers (FIRST χ 2 = 109.6, p 0.001, SAS χ 2 = 120.3, p 0.001). FIRST was best predicted by DBAS ( p 0.001), PSQI ( p 0.001), and SAS by PSQI ( p 0.001), ISI ( p 0.05), BDI ( p 0.001). In the sleep onset subgroup FIRST was related to ISI, PSQI, and DBAS and in the combined subgroup with DBAS. In both subgroups SAS was related to PSQI, ISI, and BDI. Conclusions Findings suggest potential implications: (1) among the factors that may contribute to insomnia, stress-related sleep reactivity, and psychological factors, such as anxiety symptoms, may distinguish insomnia subjects from good sleepers; (2) sleep reactivity and sleep-related cognitions seem interrelated, unhelpful beliefs may affect the stress reactivity; (3) psychological factors may influence sleep quality and the severity of insomnia; (4) these important sleep-related variables may have similar associations in insomnia subgroups; they may constitute the core factors for insomnia development and maintenance.

Insomnia is one of the most prevalent health complaints afflicting approximately 10 % of the population in Western industrialized countries at a clinical level. Despite the proposition that both biological and psychological factors play a role in the experience of insomnia, the field continues to puzzle over so-called “discrepancies” between objective and subjective measurements of sleep and daytime functioning. The promise of neuroimaging is to uncover physiological processes that may readily explain patient reports. However, while there has been an explosion in the number of studies investigating the neural correlates of insomnia with neuroimaging technologies, there appears to be little consistency in findings across studies. We suggest a number of methodological reasons which may, at least partially, explain variability in findings across neuroimaging studies in insomnia.

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.

Night-time sleep related cognitions have been shown to play a perpetuating role in insomnia. According to the cognitive model of insomnia day time cognitions (i.e. worry, rumination, etc.) may also contribute to it. The aim of this study was to investigate the possible role of daytime sleep-related rumination in Insomnia Disorder (n= 55, mean age 49.7±16.7 years), Obstructive Sleep Apnea Syndrome (OSAS) (n=33, mean age 58.1±10.2 years) and healthy subjects (n=33, mean age 49.8±13.9), using a set of sleep related variables which included the Daytime Insomnia Symptom Response Scale (DISRS), the Dysfunctional Beliefs about Sleep Scale (DBAS), the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI). Daytime sleep related rumination was higher in insomnia when compared to both OSAS (p

Summary Chronic insomnia is defined by difficulties in falling asleep, maintaining sleep, and early morning awakening, and is coupled with daytime consequences such as fatigue, attention deficits, and mood instability. These symptoms persist over a period of at least 3 months (Diagnostic and Statistical Manual 5 criteria). Chronic insomnia can be a symptom of many medical, neurological, and mental disorders. As a disorder, it incurs substantial health-care and occupational costs, and poses substantial risks for the development of cardiovascular and mental disorders, including cognitive deficits. Family and twin studies confirm that chronic insomnia can have a genetic component (heritability coefficients between 42% and 57%), whereas the investigation of autonomous and central nervous system parameters has identified hyperarousal as a final common pathway of the pathophysiology, implicating an imbalance of sleep–wake regulation consisting of either overactivity of the arousal systems, hypoactivity of the sleep-inducing systems, or both. Insomnia treatments include benzodiazepines, benzodiazepine-receptor agonists, and cognitive behavioural therapy. Treatments currently under investigation include transcranial magnetic or electrical brain stimulation, and novel methods to deliver psychological interventions.

SUMMARY A case with transient, almost complete sleep loss caused by cerebral manifestation of Whipple's disease (WD) is presented. Cerebral WD is rare and in most cases occurs after gastrointestinal infection. In our case, a progressive and finally almost complete sleep loss was the initial and predominant symptom. Polysomnographic studies in several consecutive nights and over 24 h showed a total abolition of the sleep–wake cycle with nocturnal sleep duration of less than 15 min. Endocrine tests revealed hypothalamic dysfunction with flattening of circadian rhythmicity of cortisol, TSH, growth hormone and melatonin. Cerebrospinal fluid (CSF) hypocretin was reduced. [18F]Deoxyglucose positron emission tomography (FDG-PET) revealed hypermetabolic areas in cortical and subcortical areas including the brainstem, which might explain sleep pathology and vertical gaze palsy. In the course of treatment with antibiotics and additional carbamazepine for 1 year, insomnia slowly and gradually improved. Endocrine investigations at 1-year follow-up showed persistent flattening of circadian rhythmicity. The FDG-PET indicated normalized metabolism in distinct regions of the brain stem which paralleled restoration of sleep length. The extent of sleep disruption in this case of organic insomnia was similar to cases of familial fatal insomnia, but was at least partially reversible with treatment.

The neuropeptide substance P (SP) has been supposed to be involved in the etiopathology of affective disorders, mainly because of the finding of increased levels of SP in the cerebrospinal fluid of depressed patients and the preliminary evidence of antidepressant effects of SP-receptor antagonists in depressed patients. We investigated whether SP may induce changes of sleep, mood and neuroendocrine measures that are similar to those in depressed patients. In a double-blind, randomized cross-over design, 12 healthy young men were investigated in two blocks of three consecutive nights, in which SP or NaCl was intravenously infused during the third night. Polysomnographic recordings were obtained during all nights and blood samples were drawn every 30 min during the third night. Infusion of SP caused a significant worsening of the mood of the subjects, led to an increase of REM latency and time awake during the SP-infusion intervals, caused increased stage 1 sleep in the first part of the night, and led to increased cortisol and thyroid stimulating hormone levels and a trend for decreased growth hormone levels. These effects can be interpreted as evidence for a central arousing effect of SP. Further studies should focus on the effects of substance P in patients with depressive or other psychiatric disorders.

Objective: Psychometric evaluation of the Pittsburgh Sleep Quality Index (PSQI) for primary insomnia. Methods: The study sample consisted of 80 patients with primary insomnia (DSM-IV). The length of the test–retest interval was either 2 days or several weeks. Validity analyses were calculated for PSQI data and data from sleep diaries, as well as polysomnography. To evaluate the specificity of the PSQI, insomnia patients were compared with a control group of 45 healthy subjects. Results: In primary insomnia patients, the overall PSQI global score correlation coefficient for test–retest reliability was .87. Validity analyses showed high correlations between PSQI and sleep log data and lower correlations with polysomnography data. A PSQI global score >5 resulted in a sensitivity of 98.7 and specificity of 84.4 as a marker for sleep disturbances in insomnia patients versus controls. Conclusion: The PSQI has a high test–retest reliability and a good validity for patients with primary insomnia. D 2002 Elsevier Science Inc. All rights reserved.

Question of the study Chronic insomnia afflicts approximately 5–10% of the adult population in Western industrialized countries. Insomnia may be secondary, i. e. triggered and/or maintained by psychiatric/organic illnesses or the intake of prescribed/illicit drugs. It can also occur as primary insomnia, due to a psychophysiological hyperarousal process. This review article aims at analysing the literature on the consequences of chronic primary insomnia to delineate the sequenlae of ‘pure’ insomnia with respect to performance and to psychiatric and medical morbidity.

Objective To evaluate the effect of short-term training of general practitioners (GPs) on their diagnosis and treatment of chronic insomnia. Methods A three-step randomized control group design was used: After baseline evaluation (T1) a group of 9 GPs underwent a training of half a day, while 7 GPs served as a control group. The diagnostic and therapeutic handling of insomnia patients was reevaluated under obligatory use of a structured diagnostic questionnaire (T2) and under optional use of it (T3). Results From 16 general practices, 4,754 patients were included. The frequency rate of insomnia was 19.3 %. The lowest diagnostic and treatment rate was found for insomnia patients without comorbidity (15 % at T1). Systematic non-pharmacological treatment was not offered by the GPs. At T2 the diagnosis rate increased significantly from 37.9 % (T1) to 71.5 % (T2, p = 0.038). It fell back to lower levels at T3 but remained better than at T1. At T3 non-pharmacological treatments and referral to a sleep expert were advised more often. Conclusion Short-term training of GPs can significantly improve their diagnostic sensitivity and first-line treatment efforts against insomnia.

In the present study, we evaluated the impact of are and gender on EEG spectral power of non rapid eye movement (NREM) sleep in Major depression and hypothesized a gender-dependent age effect as previously observed in healthy controls (more prominent decline of delta activity in male than in female subjects). We spectrally analyzed the NREM sleep EEG of 11 male and 11 female depressed patients, who were carefully pair-matched with regard to age and clinical parameters and were free of any psychoactive drugs for at least 1 week. Whereas male and female patients did not differ significantly in averaged spectral power, we found a significant decline of delta activity as the main age effect on sleep in men, but not in women. This clear gender-dependent age effect on the sleep EEG in Major depression contributes to a better understanding of sleep changes with aging and is methodologically important for future sleep studies in psychiatric disorders.