The potential of biomarkers for diagnosing insomnia: Consensus statement of the WFSBP Task Force on Sleep Disorders.

OBJECTIVES: Thus far, the diagnosis of insomnia is based on purely clinical criteria. Although a broad range of altered physiological parameters has been identified in insomniacs, the evidence to establish their diagnostic usefulness is very limited. Purpose of this WFSBP Task Force consensus paper is to systematically evaluate a series of biomarkers as potential diagnostic tools for insomnia. METHODS: A newly created grading system was used for assessing the validity of various measurements in establishing the diagnosis of insomnia; these measurements originated from relevant studies selected and reviewed by experts. RESULTS: The measurements with the highest diagnostic performance were those derived from psychometric instruments. Biological measurements which emerged as potentially useful diagnostic instruments were polysomnography-derived cyclic alternating pattern, actigraphy, and BDNF levels, followed by heart rate around sleep onset, deficient melatonin rhythm, and certain neuroimaging patterns (mainly for the activity of frontal and pre-frontal cortex, hippocampus and basal ganglia); yet, these findings need replication, as well as establishment of commonly accepted methodology and diagnostic cut-off points. Routine polysomnography, EEG spectral analysis, heart rate variability, skin conductance, thermoregulation, oxygen consumption, HPA axis, and inflammation indices were not shown to be of satisfactory diagnostic value. CONCLUSIONS: Apart from psychometric instruments which are confirmed to be the gold standard in diagnosing insomnia, six biomarkers emerge as being potentially useful for this purpose.

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.

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.

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.

Insomnia and obesity.

PURPOSE OF REVIEW: Accumulating data suggest that short sleep plays a role in the development of obesity in general population. Insomnia disorder is characterized by short sleep and may persist for years. The question whether these patients have a higher risk of obesity is of socioeconomic as well as therapeutic interest. RECENT FINDINGS: Numerous recently published cross-sectional and longitudinal studies show positive as well as negative associations between short sleep and overweight. Critical reviews note several methodological limitations that weaken the assumption of short sleep duration as the potential cause for obesity. From a sleep medical perspective, a basic methodological problem is the lack of a biological cut-off for short sleep duration. Therefore, recent findings on the relation between emotional stress in short sleepers and incident of obesity opens a more promising perspective on sleep quality as a possible factor. A few studies on patients with insomnia disorder, however, do not show higher BMIs adding data to a research puzzle. SUMMARY: The relation of sleep duration and incident obesity so far has insufficient evidence base. Few data on patients with insomnia disorder do not confirm the association. Further research is necessary with focus on sleep quality instead of sleep duration.

Impaired Recognition of Facially Expressed Emotions in Different Groups of Patients with Sleep Disorders.

INTRODUCTION: Recently it has been shown that acute sleep loss has a direct impact on emotional processing in healthy individuals. Here we studied the effect of chronically disturbed sleep on emotional processing by investigating two samples of patients with sleep disorders. METHODS: 25 patients with psychophysiologic insomnia (23 women and 2 men, mean age: 51.6 SD; 10.9 years), 19 patients with sleep apnea syndrome (4 women and 15 men, mean age: 51.9; SD 11.1) and a control sample of 24 subjects with normal sleep (15 women and 9 men, mean age 45.3; SD 8.8) completed a Facial Expressed Emotion Labelling (FEEL) task, requiring participants to categorize and rate the intensity of six emotional expression categories: anger, anxiety, fear, happiness, disgust and sadness. Differences in FEEL score and its subscales among the three samples were analysed using ANOVA with gender as a covariate. RESULTS: Both patients with psychophysiologic insomnia and patients with sleep apnea showed significantly lower performance in the FEEL test as compared to the control group. Differences were seen in the scales happiness and sadness. Patient groups did not differ from each other. CONCLUSION: By demonstrating that previously known effects of acute sleep deprivation on emotional processing can be extended to persons experiencing chronically disturbed sleep, our data contribute to a deeper understanding of the relationship between sleep loss and emotions.

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.

Psychophysiological Associations between Chronic Tinnitus and Sleep: A Cross Validation of Tinnitus and Insomnia Questionnaires.

BACKGROUND: The aim of the present study was to assess the prevalence of insomnia in chronic tinnitus and the association of tinnitus distress and sleep disturbance. METHODS: We retrospectively analysed data of 182 patients with chronic tinnitus who completed the Tinnitus Questionnaire (TQ) and the Regensburg Insomnia Scale (RIS). Descriptive comparisons with the validation sample of the RIS including exclusively patients with primary/psychophysiological insomnia, correlation analyses of the RIS with TQ scales, and principal component analyses (PCA) in the tinnitus sample were performed. TQ total score was corrected for the TQ sleep items. RESULTS: Prevalence of insomnia was high in tinnitus patients (76%) and tinnitus distress correlated with sleep disturbance (r = 0.558). TQ sleep subscore correlated with the RIS sum score (r = 0.690). PCA with all TQ and RIS items showed one sleep factor consisting of all RIS and the TQ sleep items. PCA with only TQ sleep and RIS items showed sleep- and tinnitus-specific factors. The sleep factors (only RIS items) were sleep depth and fearful focusing. The TQ sleep items represented tinnitus-related sleep problems. DISCUSSION: Chronic tinnitus and primary insomnia are highly related and might share similar psychological and neurophysiological mechanisms leading to impaired sleep quality.

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.

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.

Are dysfunctional attitudes and beliefs about sleep unique to primary insomnia?

OBJECTIVE: Dysfunctional thinking about sleep is a central aspect in the perpetuation of primary insomnia and a target symptom of cognitive behavioral therapy for insomnia (CBT-I). Insomnia symptoms also occur in other sleep disorders, but it is not known to what extent it is related to dysfunctional thinking about sleep. METHODS: The Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS) was administered to inpatients at a sleep center. The following groups were included: 34 patients with primary insomnia (PI), 30 patients with sleep apnea syndrome (SAS), 31 patients with restless legs syndrome (RLS), 26 patients with SAS comorbid with RLS (SAS + RLS), and 24 patients with idiopathic hypersomnia or narcolepsy. Eighty-four healthy subjects served as a control group. The DBAS scores were compared across the different sleep disorders and correlated with polysomnographic (PSG) variables, subjective sleep parameters, scores of the Beck Depression Inventory (BDI), and the Regensburg Insomnia Scale (RIS; measuring psychological symptoms of insomnia). RESULTS: Compared to healthy controls, DBAS scores were increased in PI, RLS and RLS + SAS. There was a low correlation between DBAS scores and PSG variables, moderate correlations between DBAS and subjective sleep parameters and BDI scores (r = 0.528), and a high correlation between DBAS and the RIS score (r = 0.603). CONCLUSION: The observation of increased DBAS scores in other sleep disorders besides primary insomnia underscores the usefulness of a broadened diagnostic procedure and suggests that CBT-I modules may be a complementary treatment tool for these disorders.

Regensburg Insomnia Scale (RIS): a new short rating scale for the assessment of psychological symptoms and sleep in insomnia; study design: development and validation of a new short self-rating scale in a sample of 218 patients suffering from insomnia and 94 healthy controls.

BACKGROUND: The Regensburg Insomnia Scale (RIS) is a new self-rating scale to assess cognitive, emotional and behavioural aspects of psychophysiological insomnia (PI) with only ten items. A specific purpose of the new scale is the evaluation of the outcome of insomnia- specific cognitive behaviour therapy (CBT-I). METHODS: Internal consistency of the RIS has been validated in 218 patients with PI. For determining sensitivity and specificity, this sample has been compared to 94 healthy controls. Sensitivity to change and pre-post cross-validation with the Pittsburgh Sleep Quality Index (PSQI) has been tested in a separate sample of 38 patients with PI undergoing CBT-I. RESULTS: RIS distinguishes well between controls and patients with PI. Internal consistency was within a good range (Cronbach alpha = .890). RIS was sensitive for detecting improvements after CBT-I in sleep parameters and target symptoms such as sleep-related thinking. CONCLUSION: The RIS is a valid and feasible instrument for assessing psychological PI-symptoms and sleep parameters.

Insomnia symptoms influence CPAP compliance.

PURPOSE: The aim of this study is to determine parameters which influence 6-month compliance of continuous positive airway pressure therapy (CPAP) in patients with obstructive sleep apnea syndrome (OSAS). METHODS: This prospective study investigated 73 patients (24 females) with OSAS and medical indication for CPAP therapy: age 55.1 ± 11.5 years, body mass index (BMI) 30.8 ± 5.0 kg/m2, Apnea-Hypopnea Index (AHI) 39.2 ± 26.7/h, Oxygen Desaturation Index (ODI) 33.2 ± 25.4/h, minimum O(2) saturation 78.9 ± 7.6%. The influence of baseline parameters (demographic and polysomnographic data, sleeping medication intakes, BMI, psychometrics [Epworth Sleepiness Scale, Regensburg Insomnia Scale, Vigilance test and Beck Depression Inventory]) on 6-month compliance was evaluated with a correlation and a linear regression analysis. RESULTS: The baseline value of the Regensburg Insomnia Scale (RIS) predicts 6-month CPAP compliance (r = -0.376, R (2) = 0.14, p < 0.001), although no other baseline parameter correlates. Patients with a compliance of <4 h/night show higher RIS scores, i.e., more insomnia symptoms (17.6 ± 8.8) compared to those with ≥4 h/night (12.6 ± 6.9; p < 0.05). CONCLUSIONS: Insomnia symptoms prior to the beginning of CPAP treatment show a negative influence on CPAP compliance. Further studies should clarify, if a treatment of insomnia symptoms leads to a benefit in compliance.

Polysomnography reveals unexpectedly high rates of organic sleep disorders in patients with prediagnosed primary insomnia.

OBJECTIVE: It is a matter of debate whether patients with primary insomnia require a polysomnographic examination in order to exclude specific sleep disorders such as sleep apnea syndrome (SAS) or periodic limb movements (PLM). Using a prospective design, we investigated the prevalence of organic sleep disorders by means of polysomnography (PSG) in a series of patients who were previously diagnosed with primary insomnia. This diagnosis was based on a clinical exam and an ambulatory monitoring device or previous PSG. METHODS: Seventy-seven women and 16 men (mean age 55.12 ± 13.21 years) who were admitted for cognitive behavioral therapy for insomnia were evaluated by PSG including cardiorespiratory parameters and tibialis EMG. Among them, 50 patients had undergone a clinical exam by a sleep specialist; in 18 patients, actigraphy or portable monitoring had been performed to exclude SAS or PLM; 25 patients had undergone PSG in another sleep lab previously. RESULTS: In 32 patients (34% of the sample), a PSG revealed a specific sleep disorder (SAS 16; PLMD 11; both 5), resulting in therapeutic consequences for 21 patients (SAS 10; PLMD 9; both 2). SAS and PLM patients were older and SAS patients had a higher body mass index than insomnia patients without additional findings. CONCLUSION: Indications for a PSG should be handled less restrictively in the diagnostic workup of older insomnia patients since they have a higher risk of comorbid sleep disorders even in the absence of the clinical signs of SAS or PLM.

Sleep deprivation in chronic somatoform pain-effects on mood and pain regulation.

Sleep deprivation was found to exert complex effects on affective dimensions and modalities of pain perception both in healthy volunteers and patients with major depression. Considering multifaceted links between mood and pain regulation in patients with chronic somatoform pain, it is intriguing to study sleep deprivation effects for the first time in this group of patients. Twenty patients with a somatoform pain disorder according to ICD-10 diagnostic criteria were sleep-deprived for one night, followed by one recovery night. Clinical pain complaints (visual analog scale), detection- and pain thresholds (temperature and pressure) as well as mood states (Profile of Mood States) were assessed on the day prior to the experiment, on the day after sleep deprivation and on the day after recovery sleep. We found a discrepancy between significantly increased clinical pain complaints and unaltered experimental pain perception after sleep deprivation. Only the clinical pain complaints, but not the experimental pain thresholds were correlated with tiredness-associated symptoms. Total mood disturbances decreased and feelings of depression and anger improved significantly after sleep deprivation. However, these changes were not correlated with a change in clinical pain perception. We conclude that sleep deprivation may generally change the reagibility of the limbic system, but mood processing and pain processing may be affected in an opposite way reflecting neurobiological differences between emotional regulation and interoceptive pain processing.

The options available in cognitive behavioral therapy to prevent chronification of insomnia.

Insomnia is a very frequent problem among the general population, and it has a high socio-economic impact on health care management. It produces high costs because of absenteeism and accidents, and it is considered to be a risk factor for the development of psychiatric diseases and other medical disorders. However, only a low proportion of insomniacs ever seek professional help. The reasons are still unknown, but most insomniacs probably consider their problem untreatable unless they undergo a therapy with hypnotics. Knowledge about alternative therapy methods beyond sleep medication is scarce, and specialized psychotherapy is not always available. Since dysfunctional behavior and beliefs are considered to be the central perpetuating factors for primary insomnia, the role of educational programs in terms of prevention and treating mild forms of insomnia is discussed. These workshops could be a part of a step-by-step treatment of insomnia as has been proposed recently by Espie.

Tinnitus and insomnia.

Sleep problems are common in individuals with tinnitus but it is not known if they can be seen as a reaction to the acoustic percept of tinnitus disturbing normal sleep, or if there are common causes. Sleep problems further impair the quality of life of individuals with tinnitus and the impairment correlates with the severity of the tinnitus. However the nature of the relationship between tinnitus and disturbed sleep in individuals with tinnitus is not clearly understood. Preliminary studies suggest that chronically disturbed sleep (insomnia) in individuals with tinnitus that is not caused by organic disorders exists unrelated to the tinnitus. We studied the relationship between tinnitus and insomnia in a retrospective sleep study of 13 hospitalized patients with insomnia and tinnitus. Patients with sleep apnea, periodic leg movements, or a severe psychiatric disorder were excluded. We collected physiologic sleep measures (EEG, EOG, EMG, and respiration) and subjective sleep information from a morning protocol during two nights. We also obtained information about performance in sustained attention tasks and the scores of self-rated depression scale and self-rated daytime-tiredness scale. Thirteen age- and sex-matched inpatients with primary insomnia who did not have tinnitus served as controls. There were no significant differences between the physiologic data obtained in patients with tinnitus and in the controls. Both groups had low sleep efficiency but the patients with both insomnia and tinnitus had longer subjective sleep latencies than insomnia patients without tinnitus (controls). No differences were found in sustained attention tasks, subjective daytime tiredness, and depression rating scores between the two groups. Similarities between the results from these two groups suggest that sleep specific psychotherapeutic methods, which are established for treating insomnia, should be further developed for the use in patients with insomnia and tinnitus.

The influence of age and sex on sleep latency in the MSLT-30--a normative study.

STUDY OBJECTIVES: The Multiple Sleep Latency Test-30 (MSLT-30) is a variation of the Multiple Sleep Latency Test with a fixed duration of 30 minutes for each of 5 test sessions. It requires less effort for reliable recording and is not susceptible to on-line scoring errors. The aim of the study was to provide normative data for the clinical use of the MSLT-30 and to evaluate the influence of age, sex, and other sociodemographic variables. DESIGN: An MSLT-30, along with measures of mood, objective, and subjective sleepiness was performed in a sample of healthy subjects in a balanced quota design. SETTING: Sleep laboratory in a sleep disorders center. PARTICIPANTS: One hundred subjects with no complaint of sleep disturbance or daytime sleepiness, 10 men and 10 women each from 5 age decades from 20 to 69 years. INTERVENTIONS: None. RESULTS: Mean latency to sleep stage 1 or any other sleep stage was 13.9 +/- 6.9 minutes. The SL-30 showed a clear quadratic association with age, with the shortest latencies in the middle age groups. No correlation was found between the mean latency to sleep stage 1 or any other sleep stage and sociodemographic variables or other measures of daytime sleepiness (Epworth Sleepiness Scale, vigilance test), mood scales, sleep quality (Pittsburgh Sleep Quality Index), and amount of prior sleep. CONCLUSIONS: Sleep latencies in normal subjects are age dependent in a quadratic fashion, with a minimum in middle-aged subjects. This reconciles the findings of a long mean sleep latency in the MSLT of adolescents and of an increase on the mean sleep latency with age in adults.