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.

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.

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.

Restless Legs Syndrome Prevalence and Clinical Correlates Among Psychiatric Inpatients: A Multicenter Study.

Background: There are only limited reports on the prevalence of restless legs syndrome (RLS) in patients with psychiatric disorders. The present study aimed to evaluate the prevalence and clinical correlates in psychiatric inpatients in Germany and Switzerland. Methods: This is a multicenter cross-sectional study of psychiatric inpatients with an age above 18 years that were diagnosed and evaluated face-to-face using the International RLS Study Group criteria (IRLSSG) and the International RLS severity scale (IRLS). In addition to sociodemographic and biometric data, sleep quality and mood were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Patient Health Questionnaire (PHQ-9). In addition to univariate statistics used to describe and statistically analyze differences in variables of interest between patients with and without RLS, a logistic model was employed to identify predictors for the occurrence of RLS. Results: The prevalence of RLS in a sample of 317 psychiatric inpatients was 16.4%, and 76.9% of these were diagnosed with RLS for the first time. RLS severity was moderate to severe (IRLS ± SD: 20.3 ± 8.4). The prevalences in women (p = 0.0036) and in first-degree relatives with RLS (p = 0.0108) as well as the body mass index (BMI, p = 0.0161) were significantly higher among patients with RLS, while alcohol consumption was significantly lower in the RLS group. With the exception of atypical antipsychotics, treatment with psychotropic drugs was not associated with RLS symptoms. Regarding subjective sleep quality and mood, scores of the PSQI (p = 0.0007), ISI (p = 0.0003), and ESS (p = 0.0005) were higher in patients with RLS, while PHQ-9 scores were not different. A logistic regression analysis identified gender (OR 2.67; 95% CI [1.25; 5.72]), first-degree relatives with RLS (OR 3.29; 95% CI [1.11; 9.73], ESS score (OR 1.09; 95% CI [1.01; 1.17]), and rare alcohol consumption (OR 0.45; 95% CI [0.22; 0.94] as predictors for RLS. Conclusions: Clinically significant RLS had a high prevalence in psychiatric patients. RLS was associated with higher BMI, impaired sleep quality, and lower alcohol consumption. A systematic assessment of restless legs symptoms might contribute to improve the treatment of psychiatric patients.

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.

Computer-Assisted Avatar-Based Treatment for Dysfunctional Beliefs in Depressive Inpatients: A Pilot Study.

Dysfunctional cognitions are a crucial part of depression. Cognitive therapy aims to modify dysfunctional beliefs. Typically, dysfunctional beliefs are questioned, and patients are trained to think of alternative functional beliefs. We developed a computer-assisted, avatar-based adjunct for cognitive therapy that aims to reduce dysfunctional beliefs and symptom severity. Besides, it aims to promote alternative functional beliefs. In a randomized controlled trial with 34 patients diagnosed with major depression currently undergoing inpatient treatment at the university psychiatric hospital in Regensburg, Germany, participants were randomly assigned to receive either treatment as usual (TAU) or computer-assisted avatar-based treatment for dysfunctional beliefs (CAT-DB) in addition to TAU. In CAT-DB participants are faced with a virtual avatar expressing their personal dysfunctional beliefs. Participants are asked to contradict these and express alternative functional beliefs. Assessments of conviction of dysfunctional beliefs, functional beliefs and symptom severity were done shortly before the intervention (pre-treatment), right after the intervention (post-treatment) and 14 days later (follow-up). The reduction in conviction of dysfunctional beliefs and symptom severity, and the increase in conviction of alternative functional beliefs at post-treatment and follow-up were significantly greater for the group receiving CAT-DB. Our study provides an indication in favor of the effectiveness of CAT-DB for depressive patients. It is a simple tool that could support classical cognitive therapy. Further studies at different centres, with larger sample sizes and varying therapeutic contexts are required to prove the effectiveness of our intervention.

A direct comparison of neuronavigated and non-neuronavigated intermittent theta burst stimulation in the treatment of depression.

OBJECTIVE: To investigate whether a four-week course of neuronavigated intermittent theta burst stimulation (iTBS) of the left dorsolateral prefrontal cortex is superior to the non-neuronavigated F3-EEG method of positioning. METHODS: We conducted a single-center, two-arm, randomized and double-blinded study (clinicaltrials.gov NCT03953521). 37 inpatients with an at least moderate depressive episode were randomized to receive either neuronavigated or 10-20-EEG-system based F3 guided iTBS. Both groups received twenty week daily sessions of iTBS while continuing to receive standard-of-care treatment by their ward physicians. For navigated iTBS, we used magnetic resonance imaging to target the border between the anterior and middle third of the middle frontal gyrus considered to represent the left dorsolateral prefrontal cortex (lDLPFC). Differences in the treatment arms were blinded by completely mimicking the procedures of the respective other treatment group. Rating physicians were not involved in the treatment procedure. Primary outcome was defined as the change of the 21-item version of the Hamilton Depression Score (HAMD) from baseline to end of treatment at week 4. Secondary outcomes included HAMD score during the treatment, Patient Health Questionnaire-9, WHO Quality of Life-BREF and Clinical Global Impression. For primary outcome, we used a planned group comparison for the absolute change in the HAMD. For secondary outcome measures we calculated analyses of variance (ANOVAs) with the within-subjects factor time (primary: baseline vs. week 4; secondary: all visits) and the between-subjects factor group (navigated vs. F3 guided group). We also did planned contrasts between both groups for all variables and all treatment and follow-up visits with the aim not to oversee any group differences. For group contrasts we used Student T-tests for metric and chi-square tests for categorial variables. Significance threshold was set to 5% uncorrected for multiple comparisons. RESULTS: Enrolment of 80 patients with interim analysis was planned. Interim analysis was performed after 37 patients (intention to treat). 6 patients dropped out, leaving 31 for analysis. With respect to primary outcome criteria, absolute change in the HAMD did not differ significantly between groups. In accordance, relative change and number of responders and remitters were not significantly different. Overall number of responders was 53% and of remitters was 60%. On a descriptive level, the results favor the clinical effects of the F3 group for the absolute and relative change in the HAMD and the number of responders. Number of remitters were exactly the same for both groups. Therefore, we decided to stop the trial due to the added burden of magnetic resonance imaging and neuronavigated treatment in relation to the effect. Secondary outcomes did also not differ significantly between groups. Patients did not differ in their baseline characteristics nor with respect to intake of medication during the trial period and all had access to the same therapeutic interventions. CONCLUSION: We noticed a high antidepressive effect of add-on iTBS treatment to standard inpatient treatment but failed to demonstrate a clinical superiority of neuronavigated localization. The non-navigated, F3 guided iTBS treatment used as a control group may be sophisticated enough to dilute potential added benefits, and the difference between the localization approaches is either negligible or too small to justify the additional efforts of navigation. The effects of concomitant treatment may mask effects, but our patient population reflects clinical reality in an inpatient setting. Further prospective studies are warranted to compare neuronavigated with surface-based approaches.

Bifrontal high-frequency transcranial random noise stimulation is not effective as an add-on treatment in depression.

BACKGROUND: Depressive disorders are linked to dysfunction in prefrontal cortical areas. Hence, non-invasive neurostimulation of the prefrontal cortex has demonstrated antidepressant efficacy. In the present study, we investigated the efficacy of high frequency transcranial random noise stimulation (hf-tRNS) as an add-on treatment for depression in a sham-controlled randomized trial. METHODS: Forty in-patients with depression were randomized and treated with real or sham hf-tRNS (100-650 Hz) with 0 mA offset. The electrodes were mounted over the left and right dorsolateral prefrontal cortex. The Hamilton Depression Rating Scale (primary outcome), the Major Depression Inventory, the Clinical Global Impression scale and the Global Assessment of Functioning scale were used for assessment at baseline, after 3 weeks of intervention (end of treatment), and 9 weeks after intervention. Safety parameters included cognitive functioning and reported side-effects. RESULTS: Comparison of real and sham treatment at the planned interim analysis showed an amelioration of symptoms in both groups for all outcomes with numeric but not statistically significant superiority of the sham arm for the primary outcome. Thus, the study was terminated prematurely after an interim analysis. There were no systematic differences with respect to safety parameters. LIMITATIONS: The negative finding might be related to the specific stimulation parameters used in this study. CONCLUSIONS: Our study suggests that prefrontal hf-tRNS is safe but not effective as an add-on treatment of depression. The challenge for future studies employing transcranial electric stimulation remains to identify effective stimulation parameters for the treatment of depression.

Dissociation of endocrine responses to the Trier Social Stress Test in Virtual Reality (VR-TSST) by the benzodiazepine alprazolam and the translocator protein 18 kDa (TSPO) ligand etifoxine.

BACKGROUND: Activity of the two major stress systems, the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal-medullary (SAM) axis, has already been shown to be modulated by different compounds that bind to the central benzodiazepine receptor. Less is known about ligands that modulate the peripheral benzodiazepine receptor - meanwhile known as the translocator protein 18 kDa (TSPO) - which constitute promising candidates in the search of novel anxiolytics. To close this gap, the present study compared the effects of the benzodiazepine alprazolam and the TSPO ligand etifoxine on responses of the HPA and SAM axes to the Trier Social Stress Test, a standardized paradigm to induce acute psychosocial stress in humans, performed in Virtual Reality (VR-TSST). METHODS: Sixty healthy males, aged between 18 and 55 years, were randomly assigned to receive either a daily dose of 1.5 mg alprazolam, 150 mg etifoxine, or placebo over five days. On the last day of intake, they were exposed to the VR-TSST. We assessed changes of salivary cortisol, allopregnanolone, (nor-) epinephrine in serum, TSPO expression in platelets as well as heart rate (HR), skin conductance level (SCL) and self-reports in response to the stress task. Repeated measures ANOVAs were conducted to examine treatment effects on these stress response variables during the course of VR-TSST. RESULTS: The response of salivary cortisol to the VR-TSST was significantly blunted in participants pre-treated with alprazolam but was not affected by etifoxine. While levels of allopregnanolone, epinephrine and norepinephrine increased in response to stress, TSPO expression decreased. None of those endocrine stress markers was affected by the active treatments, whereas TSPO expression increased after etifoxine administration over all study days. There were no effects of the two anxiolytics on HR, SCL or any self-report measurement. CONCLUSION: The current study confirmed the attenuating effects of benzodiazepines on stress-induced HPA axis activity but did not reveal a comparable effect of the TSPO ligand etifoxine. The long-term consequences of a pharmacologically blunted response of the HPA axis to an acute stressor should be further elucidated. Due to the missing effects of etifoxine on stress-related parameters in our sample of healthy subjects, it might be concluded that the therapeutic effects of this TSPO ligand are restricted to stronger or pathological stress responses, respectively.

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.

Sleep Disturbances and Suicidality in Posttraumatic Stress Disorder: An Overview of the Literature.

A causal relationship between sleep disturbances and suicidal behavior has been previously reported. Insomnia and nightmares are considered as hallmarks of posttraumatic stress disorder (PTSD). In addition, patients with PTSD have an increased risk for suicidality. The present article gives an overview about the existing literature on the relationship between sleep disturbances and suicidality in the context of PTSD. It aims to demonstrate that diagnosing and treating sleep problems as still underestimated target symptoms may provide preventive strategies with respect to suicidality. However, heterogeneous study designs, different samples and diverse outcome parameters hinder a direct comparison of studies and a causal relationship cannot be shown. More research is necessary to clarify this complex relationship and to tackle the value of treatment of sleep disturbances for suicide prevention in PTSD.

[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.

Cognitive behavioral treatment for insomnia is equally effective in insomnia patients with objective short and normal sleep duration.

BACKGROUND: It has been suggested that insomnia patients with short sleep duration and insomnia patients with normal sleep duration may respond differently to cognitive behavioral treatment for insomnia (CBT-I). To evaluate this hypothesis, we retrospectively examined a large sample of patients with chronic insomnia regarding their outcome post-treatment and six months after participating in a two-week standardized inpatient CBT-I program. OBJECTIVES: Seventy-two women and 20 men with chronic insomnia received standardized inpatient CBT-I and were examined with three nights of polysomnography (two baseline nights and one post-treatment night directly following the two-week treatment). Follow-up measurements of subjective insomnia symptoms were conducted after six months. The CBT-I outcome was compared between insomnia patients with polysomnographically determined short (< 6 h) and normal (≥ 6 h) sleep duration. RESULTS: Concerning subjective outcomes, CBT-I was equally effective in insomnia patients with objective short and normal sleep duration. Secondary analyses of polysomnographic data collected at post-treatment revealed that insomnia patients with short sleep duration showed a better treatment response in comparison to those with normal sleep duration. CONCLUSIONS: These results suggest that the distinction in insomnia between objective short and normal sleep duration may be of limited value for treatment decisions regarding CBT-I. However, as the overall picture of the literature on this issue is not conclusive, we conclude that further prospective research is necessary to investigate the clinical validity of phenotyping insomnia patients by objective sleep data.

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.

[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.

Changes in Subjective-Objective Sleep Discrepancy Following Inpatient Cognitive Behavior Therapy for Insomnia.

Discrepancy between objective and subjective sleep parameters is a frequent symptom in persons suffering from insomnia. Since it has an impairing effect on daytime well-being and neglects possible positive objective improvements, it would be useful if it was treated. Apart from hypnotics, cognitive behavior therapy (CBT-I) is the therapy of choice for chronic forms of insomnia. However, there is limited information about whether CBT-I can also improve subjective-objective sleep discrepancy. We investigated a large sample of patients showing chronic forms of insomnia regarding their subjective-objective sleep discrepancy pre and post CBT-I. Objective sleep data were obtained from 3 nights (2 baseline nights and 1 night after therapy) using polysomnography in our sleep laboratory. All 92 patients participated in a 14-day inpatient program with CBT-I including psychoeducation about subjective-objective sleep discrepancy. Repeated measures analyses showed an improvement in subjective-objective sleep discrepancy parameters after CBT-I. Those parameters were also correlated with perceived quality of sleep. We conclude that CBT-I is a useful tool to improve subjective-objective sleep discrepancy in patients showing chronic forms of insomnia.

Emotion introspection and regulation in depression.

Depressed patients suffer from an impairment to voluntarily influence and regulate their unpleasant emotional state. Strengthening the mental ability to interfere with dysfunctional emotion processing may be beneficial in treating depression. According to models of emotion processing this may be done by successful down-regulation of enhanced amygdala activity. We investigated short periods of intentional emotion-introspection compared with cognitive self-reflection as two domains of self-awareness in terms of effects on emotion regulation. Thirty depressed patients performed twelve second periods of emotion-introspection, self-reflection and a neutral condition during functional magnetic resonance imaging. We analyzed brain activation in the patients with depression by means of whole brain, region of interest and connectivity analyses. Amygdala activity decreased during emotion-introspection relative to self-reflection and to the neutral condition, whereby left amygdala was inversely activated relative to the left insula. Insula activity itself was correlated with medial and dorsolateral prefrontal cortex (PFC) activation. In conclusion, depressed patients are able to down-regulate amygdala activity by emotion-introspection. This may be interpreted as well-working emotion regulation supposedly induced by PFC connections mediated via insula. The finding supports the application of emotion-introspection, a mindfulness-related process, in a clinical setting as an element of psychotherapy to train and improve emotion regulation.

Daytime sleepiness versus fatigue in patients with multiple sclerosis: A systematic review on the Epworth sleepiness scale as an assessment tool.

Fatigue is a frequent and distressing symptom in patients with multiple sclerosis (MS). In contrast, sleepiness, characterized by difficulties to stay awake and alert during the day, seems to be less prevalent in MS; however, exact studies are lacking. In addition, there is a semantic confusion of the concepts of "fatigue" and "sleepiness", which are often used interchangeably. We conducted a systematic review of studies using the Epworth sleepiness scale (ESS) for the assessment of daytime sleepiness in patients with MS. The summarized results of 48 studies demonstrate that sleepiness, as indicated by elevated ESS scores, is less prevalent and less severe than fatigue but is present in a significant proportion of patients with MS. In most cross-sectional and longitudinal studies, there was a moderate association between ESS scores and various fatigue rating scales. Longitudinal studies on the effect of wakefulness-promoting agents failed to show a consistent improvement of sleepiness or fatigue as compared to placebo. It has also been shown that daytime sleepiness is frequently associated with comorbid sleep disorders that are often underrecognized and undertreated in MS. Sleepiness and potential sleep disorders may also precipitate and perpetuate fatigue in patients with MS and should be part of the differential diagnostic assessment. To support an appropriate decision-making process, we propose a stepwise evaluation of sleepiness as compared to fatigue in patients with MS.

Insomnia in patients with chronic tinnitus: Cognitive and emotional distress as moderator variables.

INTRODUCTION: Tinnitus is often associated with disturbed sleep, but there are also patients without sleep problems. The mechanisms for developing insomnia or not in tinnitus patients are still unknown. The aim of the present study was to extract possible tinnitus specific factors that increase the risk of developing insomnia based on the analysis of a large patient cohort suffering from chronic tinnitus. METHOD: 173 patients presenting at the multidisciplinary tinnitus center of a University Hospital completed a questionnaire measuring specific psychological symptoms of insomnia (RIS) and a tinnitus questionnaire (TQ). The scores of all ten RIS items were compared between tinnitus patients and 94 healthy individuals by separate ANOVAs in order to specify the extent of insomnia specific symptoms in the tinnitus group. In a second step a multiple linear regression analysis was performed in the tinnitus sample with subscales of the TQ (excluding the TQ sleep scale), age and duration of tinnitus as independent variables and the RIS score as the dependent variables. RESULTS: Tinnitus patients differed from healthy controls not only in impaired sleep quality but also in insomnia specific concerns and anxiety. Tinnitus related emotional and cognitive distress and somatic complaints correlated with severity of insomnia, whereas no association of age or duration of tinnitus with severity of insomnia was found. CONCLUSION: Our results suggest that chronic tinnitus patients have more sleeping difficulties and associated worries about sleep or negative emotions in contrast to healthy controls. Tinnitus-related distress is related to insomnia.