GABAergic Effects of Etifoxine and Alprazolam Assessed by Double Pulse TMS.

INTRODUCTION: There is a need for novel anxiolytics with improved side effect profiles compared to benzodiazepines. A promising candidate with alternative pharmacodynamics is the translocator protein ligand, etifoxine. METHODS: To get further insight into its mechanisms of action and side effects compared to the benzodiazepine alprazolam, we performed a double-blind, placebo-controlled, repeated-measures study in 36 healthy male subjects. Participants were examined for trait anxiety and side effects and underwent repeated transcranial magnetic stimulation (TMS) assessments, including motor evoked potentials (MEP), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). RESULTS: We observed attenuation of MEPs by alprazolam but not by etifoxine. SICI was not significantly affected by alprazolam or etifoxine. However, the response pattern indicated a lowered SICI threshold after the administration of etifoxine and alprazolam compared to the placebo. ICF and CSP were influenced by neither medication. Alprazolam led to higher sedation and subjective impairment of concentration compared to etifoxine. Individual anxiety trait scores did not affect TMS parameters. DISCUSSION: This study indicated a favorable side effect profile of etifoxine in healthy volunteers. Moreover, it revealed differential GABA-related effects on neuromuscular function by means of TMS. The side effects and TMS profile of etifoxine are compatible with the involvement of neurosteroidogenesis and a predominant α3 subunit modulation compared to alprazolam.

The Many Faces of Sleep Disorders in Post-Traumatic Stress Disorder: An Update on Clinical Features and Treatment.

Sleep disorders and nightmares are core symptoms of post-traumatic stress disorder (PTSD). The relationship seems to be bidirectional, and persistent disturbed sleep may influence the course of the disorder. With regard to sleep quality, insomnia and nocturnal anxiety symptoms, as well as nightmares and stressful dreams, are the most prominent sleep symptoms. Polysomnographic measurements reveal alterations of the sleep architecture and fragmentation of rapid eye movement sleep. In addition, sleep disorders, such as sleep-related breathing disorders and parasomnias are frequent comorbid conditions. The complex etiology and symptomatology of trauma-related sleep disorders with frequent psychiatric comorbidity require the application of multimodal treatment concepts, including psychological and pharmacological interventions. However, there is little empirical evidence on the effectiveness of long-term drug treatment for insomnia and nightmares. For nondrug interventions, challenges arise from the current lack of PTSD-treatment concepts integrating sleep- and trauma-focused therapies. Effective therapy for sleep disturbances may consequently also improve well-being during the day and probably even the course of PTSD. Whether early sleep interventions exert a preventive effect on the development of PTSD remains to be clarified in future studies.

Association of Chemokine (C-C Motif) Receptor 5 and Ligand 5 with Recovery from Major Depressive Disorder and Related Neurocognitive Impairment.

INTRODUCTION: Inflammatory processes play an important role in the pathophysiology of major depressive disorder (MDD), but their relevance for specific symptoms such as neurocognitive impairment is rarely investigated. METHODS: In this observational study, we investigated the changes of leukocyte chemokine (C-C motif) receptor 5 (CCR5) and ligand 5 (CCL5) mRNA levels and inflammatory cytokines in 60 MDD patients before (PRE) and after 5 weeks (W5) of antidepressive treatment in relation to therapy response and alterations in cognitive functions by means of the Cambridge Neuropsychological Test Automated Battery (CANTAB). We hypothesized that elevated CCR5 and CCL5 levels in depressed patients would decrease upon treatment and could differ with regard to cognitive impairment associated with MDD. RESULTS: Both CCR5 and CCL5 levels were significantly decreased in the responder group compared to nonresponders even before treatment. The cytokine IL-6 as a marker of inflammation in depression did not show a difference before treatment in future responders versus nonresponders, but decreased significantly upon antidepressive therapy. Regarding neurocognitive impairment in MDD patients, an increased misperception of the emotion "anger" after 5 weeks of treatment proved to be associated with a more pronounced change in CCR5, and the perception of the emotion "disgust" became faster along with a stronger decrease in CCL5 over the same time. Executive functions typically impaired in MDD patients were not markedly associated with alterations in CCR5/CCL5. DISCUSSION: CCR5 and CCL5 are important in the targeting of immune cells by HIV. This is the first study providing valuable hints that both CCR5 and CCL5 might also serve as markers of therapy response prediction in MDD. Regarding neurocognitive impairment in depression, CCR5 and CCL5 did not reveal characteristic changes upon MDD treatment such as executive functions, which are probably delayed. However, changes of emotional perception appear to be an earlier responding feature.

Sleep apnea syndrome comorbid with and without restless legs syndrome: differences in insomnia specific symptoms.

OBJECTIVE: Sleep Apnea Syndrome (SAS) is frequently comorbid with Restless Legs Syndrome (RLS). Both disorders are associated with disturbed sleep. However, data about insomnia specific symptoms in patients suffering from both sleep disorders (SAS-RLS) are rare. METHODS: In a restrospective design, we investigated 202 patients suffering from SAS and SAS-RLS. All patients underwent polysomnography, performed a vigilance test (Quatember-Maly), and completed the Regensburg Insomnia Scale (RIS), Epworth Sleepiness Scale (ESS), Beck Depression Inventory-II (BDI-II), and a Morning Questionnaire (FZN). Differences in insomnia specific symptoms between SAS and SAS-RLS were calculated using ANOVA. In a secondary analysis, the differences in daytime sleepiness and depression were analyzed. RESULTS: Of 202 patients, 42 (21%) had SAS-RLS. The proportion of women (60%) with SASRLS was higher than for men (40%) while men had had a higher proportion (71%) of SAS alone compared to women (29%), p < 0.0005. The RIS score was higher in SAS-RLS than in SAS. No differences were found in PSG data, ESS, BDI-II, or vigilance tests. CONCLUSIONS: Patients with both disorders SAS and RLS show a higher degree of insomnia-specific symptoms than for SAS alone and may profit from additional insomnia specific treatment.

Crawling the German Health Web: Exploratory Study and Graph Analysis.

BACKGROUND: The internet has become an increasingly important resource for health information. However, with a growing amount of web pages, it is nearly impossible for humans to manually keep track of evolving and continuously changing content in the health domain. To better understand the nature of all web-based health information as given in a specific language, it is important to identify (1) information hubs for the health domain, (2) content providers of high prestige, and (3) important topics and trends in the health-related web. In this context, an automatic web crawling approach can provide the necessary data for a computational and statistical analysis to answer (1) to (3). OBJECTIVE: This study demonstrates the suitability of a focused crawler for the acquisition of the German Health Web (GHW) which includes all health-related web content of the three mostly German speaking countries Germany, Austria and Switzerland. Based on the gathered data, we provide a preliminary analysis of the GHW's graph structure covering its size, most important content providers and a ratio of public to private stakeholders. In addition, we provide our experiences in building and operating such a highly scalable crawler. METHODS: A support vector machine classifier was trained on a large data set acquired from various German content providers to distinguish between health-related and non-health-related web pages. The classifier was evaluated using accuracy, recall and precision on an 80/20 training/test split (TD1) and against a crowd-validated data set (TD2). To implement the crawler, we extended the open-source framework StormCrawler. The actual crawl was conducted for 227 days. The crawler was evaluated by using harvest rate and its recall was estimated using a seed-target approach. RESULTS: In total, n=22,405 seed URLs with country-code top level domains .de: 85.36% (19,126/22,405), .at: 6.83% (1530/22,405), .ch: 7.81% (1749/22,405), were collected from Curlie and a previous crawl. The text classifier achieved an accuracy on TD1 of 0.937 (TD2=0.966), a precision on TD1 of 0.934 (TD2=0.954) and a recall on TD1 of 0.944 (TD2=0.989). The crawl yields 13.5 million presumably relevant and 119.5 million nonrelevant web pages. The average harvest rate was 19.76%; recall was 0.821 (4105/5000 targets found). The resulting host-aggregated graph contains 215,372 nodes and 403,175 edges (network diameter=25; average path length=6.466; average degree=1.872; average in-degree=1.892; average out-degree=1.845; modularity=0.723). Among the 25 top-ranked pages for each country (according to PageRank), 40% (30/75) were web sites published by public institutions. 25% (19/75) were published by nonprofit organizations and 35% (26/75) by private organizations or individuals. CONCLUSIONS: The results indicate, that the presented crawler is a suitable method for acquiring a large fraction of the GHW. As desired, the computed statistical data allows for determining major information hubs and important content providers on the GHW. In the future, the acquired data may be used to assess important topics and trends but also to build health-specific search engines.

[Internet-based cognitive behavioral therapy of insomnia and nightmare disorder]. / Internetbasierte kognitive Verhaltenstherapie der Insomnie und Albtraumstörung.

Cognitive behavioral therapeutic interventions are considered to be one of the most effective forms of treatment of various mental disorders. Besides being very frequent, sleep disorders, such as insomnia and nightmare disorder are often not treated effectively and guideline-conform, mainly due to the lack of qualified psychotherapists. Implementation of modern technical options, such as web-based psychotherapy can help to overcome this problem. This article presents the current situation in the treatment of insomnia and nightmare disorders as particularly well-suited fields of application. For insomnia there are several English language and also recently German language options, which for example were also evaluated for the application to work-related stress and sleep disorders. In this respect, procedures with and without contact to a therapist or multicomponent procedures and single interventions can be differentiated. For nightmare disorders imagery rehearsal therapy provides a structure, which can also easily be transferred to an internet-based therapy program. The currently beginning use of internet-based treatment of sleep disorders does not yet utilize all theoretically available technical possibilities. The potential of internet-based therapy is extremely versatile and it remains for medical sleep experts to consider which method can be used for which indications.

[Recommendations on performing polygraphy or polysomnography in the fields of psychiatry and psychotherapy : Position paper of the working group on sleep medicine of the German Association for Psychiatry, Psychotherapy and Psychosomatics]. / Empfehlungen zur Durchführung einer Polygraphie oder Polysomnographie im Bereich Psychiatrie und Psychotherapie : Positionspapier des DGPPN-Referats Schlafmedizin.

Difficulties in falling asleep and maintaining sleep, nonrestorative sleep and decreased daytime wakefulness represent very common but relatively unspecific health complaints. Around 100 specific sleep-related disorders will be classified in their own major chap. 7 (sleep wake disorders) for the first time in the upcoming 11th version of the International Classification of Diseases (ICD 11). With respect to the disciplines of psychiatry and psychotherapy there is a bidirectional relationship between mental health and sleep wake disorders. Sleep wake disorders can be an independent risk factor for the onset of a mental disorder and have a negative influence on the course of the disease. In addition, sleep wake disorders can also precede a mental disease as an early symptom and therefore be an important indication for early recognition. Many sleep wake disorders can be diagnosed based on the anamnesis and routine clinical investigations. In special cases, examination in a specialized sleep laboratory and treatment in a sleep medicine center following a staged care approach can be mandatory. Polysomnography represents the gold standard for the differential diagnostics; however, there is no legal foundation in the field of neuropsychiatric disorders for remuneration in the German healthcare system. This review summarizes the current guidelines with respect to the criteria for an investigation in a sleep laboratory from the perspective of the disciplines of psychiatry and psychotherapy. From this the requirements for guideline-conform diagnostics and treatment are derived.

The effect of partial sleep deprivation on computer-based measures of fitness to drive.

PURPOSE: Using a partial sleep deprivation paradigm, the aim of the study was to investigate the sensitivity of a computer-based test battery of fitness to drive to detect impairments related to sleepiness. METHODS: Forty-seven healthy subjects (34 females, mean age 26.0 ± 6.8 years) participated in a counterbalanced within-subject design of two conditions: (i) normal night sleep and (ii) partial sleep deprivation (PSD) with 4 h time in bed. For the assessment of fitness to drive, we used a validated traffic psychological test battery. Moreover, well-established measures of sleepiness highly responsive to sleep deprivation were applied: the Karolinska Sleepiness Scale (KSS), pupillography (Pupil Unrest Index (PUI) as physiological sleepiness indicator) and two sustained attention tasks (psychomotor Vigilance Task and Mackworth Clock Test). RESULTS: Subjective and physiological sleepiness were significantly increased after PSD, accompanied by large (d > 1.50 for KSS) and medium (d = 0.55 for PUI) effect sizes. Sleepiness-related performance decrements were found in both sustained attention tasks (d = 0.59-0.77). Assessing driving-related ability, PSD induced decrements only in the test domain Reaction Test (reaction time d = 0.54 and motor time d = 0.45). All other subtests-as well as the overall judgement of fitness to drive-were not significantly affected by PSD. CONCLUSION: In contrast to established tests of sustained attention and subjective sleepiness, computer-based test batteries of fitness to drive might lack sensitivity to core aspects of sleepiness as they mainly consist of short and stimulating subtests. Therefore, tasks that require sustained attention should be an essential part of traffic psychological test batteries when sleepiness is a potential issue.

Deep Brain Stimulation for Obsessive Compulsive Disorder Reduces Symptoms of Irritable Bowel Syndrome in a Single Patient.

Irritable bowel syndrome (IBS) is a frequent gastrointestinal disorder that is difficult to treat. We describe findings from evaluation of a woman (55 years old) with obsessive compulsive disorder, which was treated with bilateral deep brain stimulation in the anterior limb of the internal capsule, and IBS. After the brain stimulation treatment she reported substantial relief of her IBS symptoms. This reduction depended on specific stimulation parameters, was reproducible over time, and was not directly associated with improvements in obsessive compulsive disorder symptoms. These observations indicate a specific effect of deep brain stimulation on IBS. This observation confirms involvement of specific brain structures in the pathophysiology of IBS and shows that symptoms can be reduced through modulation of neuronal activity in the central nervous system. Further studies of the effects of brain stimulation on IBS are required.

Severe chronic insomnia is not associated with higher body mass index.

Short sleep duration is widely considered to be a risk factor for weight gain, suggesting that patients suffering from sleep disorders are a risk group. Despite some positive preliminary data on patients with organic sleep disorders, empirical evidence for an increased body mass index in patients with insomnia is scarce. Two-hundred and thirty-three patients with a confirmed diagnosis of severe and chronic insomnia without co-morbidity showing objectively impaired sleep quality were compared with respect to their body mass index with control data derived from a representative population survey matched in gender and age. As a result, patients with insomnia showed a lower body mass index (23.8 kg m(-2) versus 27.1 kg m(-2) ; P < 0.0005). Our findings suggest that patients with chronic insomnia do not exhibit overweight. These data are a valuable educational tool to calm patients' fears about the consequences of insomnia, and contribute to the understanding of chronically disturbed sleep and weight regulation.

Impact of overnight traffic noise on sleep quality, sleepiness, and vigilant attention in long-haul truck drivers: Results of a pilot study.

This study aimed to evaluate the impact of traffic noise along the motorway on sleep quality, sleepiness, and vigilant attention in long-haul truck drivers. This was a randomized, crossover, within-subject controlled study. Healthy long-haul truck drivers spent 6 consecutive nights in a real truck berth with full sleep laboratory equipment. During 3 nights, subjects were exposed to replayed traffic noise alongside motorways, whereas the other 3 nights were without traffic noise. Polysomnography was recorded during the nights and numerous sleepiness tests and vigilance examinations were performed during the following standardized working day. Outcome measures were compared between noisy and silent nights using the paired Wilcoxon test. Ten healthy long-haul truck drivers with a mean age of 36.3 ± 7.3 years completed the study as planned. On noisy nights, subjects had greater latencies to the rapid eye movement (REM) phase (90 ± 32 min vs 69 ± 16 min, P = 0.074) and higher percentages of sleep stage 1 (13.7 ± 5.5% vs 11.2 ± 4.4%; P = 0.059). Subjects also rated their sleep quality as having been better during nights without noise (28.1 ± 3.7 vs 30.3 ± 6.2, P = 0.092). The impact of these differences on daytime sleepiness and vigilance was rather low; however, mean Karolinska Sleepiness Scale (KSS) scores measured during the course of the following day were higher on six out of eight occasions after noisy nights. The effects of overnight traffic noise on sleep quality are detectable but unlikely to have any major impact on the vigilant attention and driving performance of long haul-truck drivers with low nocturnal noise sensitivity. This might not be true for subgroups prone to sleeping disorders.

Hypothalamo-pituitary-adrenal axis, glucose metabolism and TNF-α in narcolepsy.

Narcolepsy with cataplexy is caused by a deficiency in the production of hypocretin/orexin, which regulates sleep and wakefulness, and also influences appetite, neuroendocrine functions and metabolism. In this case-control study, 11 patients with narcolepsy with cataplexy and 11 healthy adults underwent an oral glucose tolerance test, and dexamethasone suppression/corticotropin-releasing hormone stimulation test. The average age of patients and controls was 35.1 ± 13.2 and 41.0 ± 2.9 years, respectively, body mass index was 28.1 ± 6.6 and 25.5 ± 4.7 kg m(-2) . We did not find evidence of a significantly increased prevalence of disturbed glucose tolerance in patients with narcolepsy. After hypothalamo-pituitary-adrenal axis suppression, the number of non-suppressors did not differ between the groups, indicating normal negative feedback sensitivity. The level of cortisol after dexamethasone suppression was significantly lower in patients with narcolepsy, suggesting a slight basal downregulation and/or a slightly increased negative feedback sensitivity of the major endocrine stress system in narcolepsy. Following corticotropin-releasing hormone stimulation, there were no significant differences in levels of adrenocorticotropic hormone or cortisol, and in adrenocortical responsivity to adrenocorticotropic hormone. Finally, patients with narcolepsy displayed significantly higher plasma levels of tumour necrosis factor alpha, soluble tumour necrosis factor receptor p55, soluble tumour necrosis factor receptor p75 and interleukin 6 after adjustment for body mass index. The present study confirms that narcolepsy by itself is not associated with disturbances of glucose metabolism, but goes along with a subtle dysregulation of inflammatory cytokine production. We also found that dynamic hypothalamo-pituitary-adrenal system response is not altered, whereas negative feedback to dexamethasone might be slightly enhanced.

The perfectly motivated nurse and the others: workplace and personal characteristics impact preference of nursing tasks.

AIMS: To identify whether motivation of nurses coincides with personal values, workplace or personal characteristics. BACKGROUND: Shortage of nursing workforce compromises patient care. Motivation and job satisfaction are factors considered to make nurses quit. Little is known about measurement and variation of nurses' motivation. Funding for human resource programmes is limited - effective programmes could focus on nurses in need of motivational support. METHODS: Exploratory study with nurses using questionnaires in an academic hospital in Germany. Work motivation was approximated through preference of nursing tasks. Questionnaires measured personal values, preference of generic nursing tasks, and workplace and personal characteristics. RESULTS: A total of 212 questionnaires were usable. Higher motivation was found in groups of nurses with the dominant personal value 'Benevolence', with high self-rated expertise, in the middle of their career or working in surgical or general wards. Motivation was low in nurses with the dominant value 'Hedonism', or nurses in internal medicine or with low to medium self-rated expertise or who used computers infrequently. CONCLUSIONS: Motivation coincided with dominant personal values, workplace and personal characteristics. The results should be validated in other settings. IMPLICATIONS FOR NURSING MANAGEMENT: Human resource programmes could focus on nurses whose motivation is at risk. Prospectively highly motivated individuals should be hired with priority.

Multimodal in-vehicle lighting system increases daytime light exposure and alertness in truck drivers under Arctic winter conditions.

Drowsiness while driving negatively impacts road safety, especially in truck drivers. The present study investigated the feasibility and alerting effects of a daylight-supplementing in-truck lighting system (DS) providing short-wavelength enriched light before, during, and after driving. In a within-participants design, eight truck drivers drove a fully-loaded truck under wintry Scandinavian conditions (low daylight levels) with a DS or placebo system for five days. Subjective and objective measures of alertness were recorded several times daily, and evening melatonin levels were recorded three times per study condition. DS significantly increased daytime light exposure without causing negative side effects while driving. In addition, no negative carry-over effects were observed on evening melatonin and sleepiness levels or on nighttime sleep quality. Moreover, objective alertness (i.e., psychomotor vigilance) before and after driving was significantly improved by bright light exposure. This effect was accompanied by improved subjective alertness in the morning. This field study demonstrated that DS was able to increase daytime light exposure in low-daylight conditions and to improve alertness in truck drivers before and after driving (e.g., during driving rest periods). Further studies are warranted to investigate the effects of daylight-supplementing in-cabin lighting on driving performance and road safety measures.

Gene expression profiling of breast cancer survivability by pooled cDNA microarray analysis using logistic regression, artificial neural networks and decision trees.

BACKGROUND: Microarray technology can acquire information about thousands of genes simultaneously. We analyzed published breast cancer microarray databases to predict five-year recurrence and compared the performance of three data mining algorithms of artificial neural networks (ANN), decision trees (DT) and logistic regression (LR) and two composite models of DT-ANN and DT-LR. The collection of microarray datasets from the Gene Expression Omnibus, four breast cancer datasets were pooled for predicting five-year breast cancer relapse. After data compilation, 757 subjects, 5 clinical variables and 13,452 genetic variables were aggregated. The bootstrap method, Mann-Whitney U test and 20-fold cross-validation were performed to investigate candidate genes with 100 most-significant p-values. The predictive powers of DT, LR and ANN models were assessed using accuracy and the area under ROC curve. The associated genes were evaluated using Cox regression. RESULTS: The DT models exhibited the lowest predictive power and the poorest extrapolation when applied to the test samples. The ANN models displayed the best predictive power and showed the best extrapolation. The 21 most-associated genes, as determined by integration of each model, were analyzed using Cox regression with a 3.53-fold (95% CI: 2.24-5.58) increased risk of breast cancer five-year recurrence. CONCLUSIONS: The 21 selected genes can predict breast cancer recurrence. Among these genes, CCNB1, PLK1 and TOP2A are in the cell cycle G2/M DNA damage checkpoint pathway. Oncologists can offer the genetic information for patients when understanding the gene expression profiles on breast cancer recurrence.

Readability and topics of the German Health Web: Exploratory study and text analysis.

BACKGROUND: The internet has become an increasingly important resource for health information, especially for lay people. However, the information found does not necessarily comply with the user's health literacy level. Therefore, it is vital to (1) identify prominent information providers, (2) quantify the readability of written health information, and (3) to analyze how different types of information sources are suited for people with differing health literacy levels. OBJECTIVE: In previous work, we showed the use of a focused crawler to "capture" and describe a large sample of the "German Health Web", which we call the "Sampled German Health Web" (sGHW). It includes health-related web content of the three mostly German speaking countries Germany, Austria, and Switzerland, i.e. country-code top-level domains (ccTLDs) ".de", ".at" and ".ch". Based on the crawled data, we now provide a fully automated readability and vocabulary analysis of a subsample of the sGHW, an analysis of the sGHW's graph structure covering its size, its content providers and a ratio of public to private stakeholders. In addition, we apply Latent Dirichlet Allocation (LDA) to identify topics and themes within the sGHW. METHODS: Important web sites were identified by applying PageRank on the sGHW's graph representation. LDA was used to discover topics within the top-ranked web sites. Next, a computer-based readability and vocabulary analysis was performed on each health-related web page. Flesch Reading Ease (FRE) and the 4th Vienna formula (WSTF) were used to assess the readability. Vocabulary was assessed by a specifically trained Support Vector Machine classifier. RESULTS: In total, n = 14,193,743 health-related web pages were collected during the study period of 370 days. The resulting host-aggregated web graph comprises 231,733 nodes connected via 429,530 edges (network diameter = 25; average path length = 6.804; average degree = 1.854; modularity = 0.723). Among 3000 top-ranked pages (1000 per ccTLD according to PageRank), 18.50%(555/3000) belong to web sites from governmental or public institutions, 18.03% (541/3000) from nonprofit organizations, 54.03% (1621/3000) from private organizations, 4.07% (122/3000) from news agencies, 3.87% (116/3000) from pharmaceutical companies, 0.90% (27/3000) from private bloggers, and 0.60% (18/3000) are from others. LDA identified 50 topics, which we grouped into 11 themes: "Research & Science", "Illness & Injury", "The State", "Healthcare structures", "Diet & Food", "Medical Specialities", "Economy", "Food production", "Health communication", "Family" and "Other". The most prevalent themes were "Research & Science" and "Illness & Injury" accounting for 21.04% and 17.92% of all topics across all ccTLDs and provider types, respectively. Our readability analysis reveals that the majority of the collected web sites is structurally difficult or very difficult to read: 84.63% (2539/3000) scored a WSTF ≥ 12, 89.70% (2691/3000) scored a FRE ≤ 49. Moreover, our vocabulary analysis shows that 44.00% (1320/3000) web sites use vocabulary that is well suited for a lay audience. CONCLUSIONS: We were able to identify major information hubs as well as topics and themes within the sGHW. Results indicate that the readability within the sGHW is low. As a consequence, patients may face barriers, even though the vocabulary used seems appropriate from a medical perspective. In future work, the authors intend to extend their analyses to identify trustworthy health information web sites.

Prospective analyses of alertness, sleep, and fitness to drive one year after de novo multiple sclerosis diagnosis.

BACKGROUND: The prevalence and functional burden of the chronic demyelinating disease multiple sclerosis (MS) are well documented; however, little is known about the initial clinical course of alertness, sleep, cognitive, and psychological symptoms. OBJECTIVES: This exploratory, prospective, longitudinal study multidimensionally investigated the development and progression of alertness, sleep, fitness to drive, and psychological symptoms in the first year after de novo MS diagnosis. METHODS: Twenty-five people with MS (pwMS) were assessed cognitively, psychologically, and using polysomnography soon after diagnosis and one year later, with outcomes compared to matched healthy controls. RESULTS: In the early stage of the disease, psychological symptoms of pwMS were comparable with those of controls, and patient conditions did not deteriorate within the first disease year. A small percentage of pwMS experienced increased levels of anxiety and depression after diagnosis. Alertness, sustained attention, and fitness to drive were comparable between both groups, and fatigue levels remained low over the course of the year. CONCLUSIONS: This study highlights patient experiences within the initial clinical course of MS in a small group of patients. Further research is needed to understand the progression of symptoms and impairments in MS over a longer period and in different stages of the disease.

Single sessions of transcranial direct current stimulation and transcranial random noise stimulation exert no effect on sleepiness in patients with narcolepsy and idiopathic hypersomnia.

Background: Hypersomnia poses major challenges to treatment providers given the limitations of available treatment options. In this context, the application of non-invasive brain stimulation techniques such as transcranial electrical stimulation (tES) may open up new avenues to effective treatment. Preliminary evidence suggests both acute and longer-lasting positive effects of transcranial direct current stimulation (tDCS) on vigilance and sleepiness in hypersomniac patients. Based on these findings, the present study sought to investigate short-term effects of single sessions of tDCS and transcranial random noise stimulation (tRNS) on sleepiness in persons suffering from hypersomnia. Methods: A sample of 29 patients suffering from narcolepsy or idiopathic hypersomnia (IH) was recruited from the Regensburg Sleep Disorder Center and underwent single sessions of tES (anodal tDCS, tRNS, sham) over the left and right dorsolateral prefrontal cortex on three consecutive days in a double-blind, sham-controlled, pseudorandomized crossover trial. The primary study endpoint was the mean reaction time measured by the Psychomotor Vigilance Task (PVT) before and directly after the daily tES sessions. Secondary endpoints were additional PVT outcome metrics as well as subjective outcome parameters (e.g., Karolinska Sleepiness Scale; KSS). Results: There were no significant treatment effects neither on objective (i.e., PVT) nor on subjective indicators of sleepiness. Conclusion: We could not demonstrate any clinically relevant effects of single sessions of tDCS or tRNS on objective or subjective measures of sleepiness in patients with hypersomnia. However, we cannot exclude that repeated sessions of tES may affect vigilance or sleepiness in hypersomniac patients.

Effects of rapid eye movement sleep deprivation on fear extinction recall and prediction error signaling.

In a temporal difference learning approach of classical conditioning, a theoretical error signal shifts from outcome deliverance to the onset of the conditioned stimulus. Omission of an expected outcome results in a negative prediction error signal, which is the initial step towards successful extinction and may therefore be relevant for fear extinction recall. As studies in rodents have observed a bidirectional relationship between fear extinction and rapid eye movement (REM) sleep, we aimed to test the hypothesis that REM sleep deprivation impairs recall of fear extinction through prediction error signaling in humans. In a three-day design with polysomnographically controlled REM sleep deprivation, 18 young, healthy subjects performed a fear conditioning, extinction and recall of extinction task with visual stimuli, and mild electrical shocks during combined functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) measurements. Compared to the control group, the REM sleep deprivation group had increased SCR scores to a previously extinguished stimulus at early recall of extinction trials, which was associated with an altered fMRI time-course in the left middle temporal gyrus. Post-hoc contrasts corrected for measures of NREM sleep variability also revealed between-group differences primarily in the temporal lobe. Our results demonstrate altered prediction error signaling during recall of fear extinction after REM sleep deprivation, which may further our understanding of anxiety disorders in which disturbed sleep and impaired fear extinction learning coincide. Moreover, our findings are indicative of REM sleep related plasticity in regions that also show an increase in activity during REM sleep.

Low Sleep Satisfaction Is Related to High Disease Burden in Tinnitus.

Previous studies have shown a high prevalence of sleep disturbances in tinnitus patients. However, no study has yet evaluated subjective sleep satisfaction. The present study aimed to investigate associations of self-reported sleep satisfaction with sociodemographic factors, tinnitus-related distress, depression, and self-reported quality of life. This is a retrospective analysis of 2344 outpatients with tinnitus presenting at a tertiary German tinnitus clinic from 2010 to 2020. Patients who filled in five questionnaires (Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), Major Depression Inventory (MDI), Tinnitus Sample Case History Questionnaire (TSCHQ), and the World Health Organization Quality of Life Brief Version (WHOQOL-Bref)) were included. Based on the question about sleep satisfaction in the WHOQOL-Bref, group classification into (I) sleep-satisfied, (II) neither satisfied or dissatisfied, and (III) sleep-dissatisfied patients was performed. Associations between sleep satisfaction and quality of life, depression, tinnitus distress, and tinnitus characteristics were analyzed by group differences and a multinomial regression model with elastic net penalization. A total of 42.38% of patients were satisfied or very satisfied with sleep, whereas 40.91% of patients were dissatisfied or very dissatisfied with sleep. The remaining patients reported being neither satisfied nor dissatisfied with sleep. Sleep-dissatisfied patients were significantly more burdened in questionnaires on depressive symptoms (MDI), tinnitus distress (TQ, THI), and quality of life (WHOQOL-Bref). In addition, they suffered significantly more often from comorbidities such as headache, neck pain, or temporomandibular joint disorder (TMJ). The elastic net regression based on sum scores of THI, TQ, MDI, the four domains of WHOQOL-Bref, as well as all individual questions from the TSCHQ was able to classify patients satisfied with their sleep with an accuracy of 79%, 87.8% sensitivity, and 70.4% specificity. The model could not identify patients indifferent with the quality of their sleep (neither satisfied nor dissatisfied) (sensitivity: 0%; specificity: 100%). The accuracy of the model to predict patients dissatisfied with their sleep was 80.7%, with 83% sensitivity and 78.4% specificity. Poor physical and mental health (Domain I/II WHOQOL-Bref) as well as tinnitus distress were the strongest predictors of sleep dissatisfaction. Conversely, for sleep satisfaction, good physical and mental health as well as low tinnitus distress were the strongest predictors. The division into sleep-satisfied and sleep-dissatisfied tinnitus patients allows a very good discrimination regarding disease burden as indicated by depression, tinnitus distress, quality of life, and pain-related comorbidities. Physical and mental health as well as tinnitus distress seem to be strongly related to sleep satisfaction underscoring the concept of "tinnitus" versus "tinnitus disorder", but also the importance of sleep satisfaction as a global health indicator. Moreover, these data indicate the relevance of addressing sleep disorders in the therapeutic management of chronic tinnitus patients.