Light Therapy With Scheduled Rise Times in Young Adults With Delayed Sleep Phase Disorder: Therapeutic Outcomes and Possible Predictors.

Clinical trials with light therapy (LT) for delayed sleep phase disorder (DSPD) are sparse and little is known about factors that are favorable for improvements. In this study, LT with scheduled rise times was conducted at home for 14 days by 44 participants with DSPD aged 16-26 years. Primary outcomes were sleep onset and sleep offset. Potential predictors were demographic characteristics, chronotype, dim light melatonin onset, the number of days the LT lamp was used, the daily duration of LT, daytime sleepiness, anxiety, depression, worry, and rumination. Significant advances were observed in sleep onset and sleep offset from baseline to the end of treatment. The number of days of LT predicted earlier sleep onset and sleep offset.

Learning and sleep-dependent consolidation of spatial and procedural memories are unaltered in young men under a fixed short sleep schedule.

OBJECTIVE: To investigate if a fixed short sleep schedule impairs one of the main functions of sleep, which is to consolidate newly learned memories. METHODS: Sixteen young men participated in two experimental conditions, each of which lasted for 3 consecutive days and nights in our laboratory: a short sleep schedule (4.25-h sleep opportunity per night) versus a normal sleep schedule (8.5h per night). In the evening after two experimental nights, participants learned locations of 15 card pairs (spatial memory task) and a procedural finger tapping sequence task. Post-sleep retrieval of both memory tasks was tested the next morning. RESULTS: The short sleep schedule, compared with the normal sleep schedule, considerably altered sleep characteristics, e.g. the proportion of time in slow-wave sleep increased across the three experimental nights. In contrast, neither learning in the evening of day 2, nor subsequent overnight memory consolidation (i.e. concerning the change in memory performance between pre-sleep learning on day 2 and post-sleep retrieval on day 3) differed between the normal and short sleep schedule conditions. CONCLUSIONS: Our findings suggest that learning in the evening and subsequent sleep-dependent consolidation of procedural and spatial memories are unaltered in young men living under a fixed short sleep schedule. Future studies are warranted to validate our findings in other groups (e.g. adolescents and older subjects) and after more prolonged chronic sleep loss paradigms.

A single night of partial sleep loss impairs fasting insulin sensitivity but does not affect cephalic phase insulin release in young men.

The present study sought to investigate whether a single night of partial sleep deprivation (PSD) would alter fasting insulin sensitivity and cephalic phase insulin release (CPIR) in humans. A rise in circulating insulin in response to food-related sensory stimulation may prepare tissues to break down ingested glucose, e.g. by stimulating rate-limiting glycolytic enzymes. In addition, given insulin's anorexigenic properties once it reaches the brain, the CPIR may serve as an early peripheral satiety signal. Against this background, in the present study 16 men participated in two separate sessions: one night of PSD (4.25 h sleep) versus one night of full sleep (8.5 h sleep). In the morning following each sleep condition, subjects' oral cavities were rinsed with a 1-molar sucrose solution for 45 s, preceded and followed by blood sampling for repeated determination of plasma glucose and serum insulin concentrations (-3, +3, +5, +7, +10 and +20 min). Our main result was that PSD, compared with full sleep, was associated with significantly higher peripheral insulin resistance, as indicated by a higher fasting homeostasis model assessment of insulin resistance index (+16%, P = 0.025). In contrast, no CPIR was observed in any of the two sleep conditions. Our findings indicate that a single night of PSD is already sufficient to impair fasting insulin sensitivity in healthy men. In contrast, brief oral cavity rinsing with sucrose solution did not change serum insulin concentrations, suggesting that a blunted CPIR is an unlikely mechanism through which acute sleep loss causes metabolic perturbations during morning hours in humans.

Cognitive Behavioral Therapy as an Adjunct Treatment to Light Therapy for Delayed Sleep Phase Disorder in Young Adults: A Randomized Controlled Feasibility Study.

Delayed sleep phase disorder (DSPD) is common among young people, but there is still no evidence-based treatment available. In the present study, the feasibility of cognitive behavioral therapy (CBT) was evaluated as an additive treatment to light therapy (LT) in DSPD. A randomized controlled trial with participants aged 16 to 26 years received LT for two weeks followed by either four weeks of CBT or no treatment (NT). LT advanced sleep-wake rhythm in both groups. Comparing LT+CBT with LT+NT, no significant group differences were observed in the primary endpoints. Although anxiety and depression scores were low at pretreatment, they decreased significantly more in LT+CBT compared to LT+NT. The results are discussed and some suggestions are given for further studies.

Initial Sleep Time Predicts Success in Manual-Guided Cognitive Behavioral Therapy for Insomnia.

Cognitive behavioral therapy produces significant and long-lasting improvement for individuals with insomnia, but treatment resources are scarce. A "stepped care" approach has therefore been proposed, but knowledge is limited on how to best allocate patients to different treatment steps. In this study, 66 primary-care patients with insomnia attended a low-end treatment step: manual-guided cognitive behavioral therapy (CBT) for insomnia delivered by ordinary primary-care personnel. Based on clinically significant treatment effects, subjects were grouped into treatment responders or nonresponders. Baseline data were analyzed to identify predictors for treatment success. Long total sleep time at baseline assessment was the only statistically significant predictor for becoming a responder, and sleep time may thus be important to consider before enrolling patients in low-end treatments.

Developing a cognitive behavioral therapy manual for delayed sleep-wake phase disorder.

This article reports the development of a treatment protocol, based on cognitive behavioral therapy (CBT) principles, for delayed sleep-wake phase disorder (DSWPD). The protocol consists of psycho-education, presenting a CBT model for DSWPD, case formulation, motivational interviewing, registering sleep in a diary, strategies to improve the rhythm of sleep and wakefulness, relaxation training, cognitive restructuring, strategies to cope with daytime symptoms, constructing an individualized CBT program, and learning how to deal with relapses. Qualitative data, focusing on how the patients perceived the protocol, were collected within the realm of a trial exploring the efficacy of the protocol. These findings highlighted several advantages but also disadvantages of the therapy. It is our hope that this paper might act as a platform for further clinical work and future research efforts in patients with DSWPD.

Acute sleep deprivation in healthy young men: impact on population diversity and function of circulating neutrophils.

Lack of sleep greatly affects our immune system. The present study investigates the acute effects of total sleep deprivation on blood neutrophils, the most abundant immune cell in our circulation and the first cell type recruited to sites of infection. Thus, the population diversity and function of circulating neutrophils were compared in healthy young men following one night of total sleep deprivation (TSD) or after 8h regular sleep. We found that neutrophil counts were elevated after nocturnal wakefulness (2.0 ± 0.2 × 10(9)/l vs. 2.6 ± 0.2 × 10(9)/l, sleep vs. TSD, respectively) and the population contained more immature CD16(dim)/CD62L(bright) cells (0.11 ± 0.040 × 10(9)/l [5.5 ± 1.1%] vs. 0.26 ± 0.020 × 10(9)/l [9.9 ± 1.4%]). As the rise in numbers of circulating mature CD16(bright)/CD62L(bright) neutrophils was less pronounced, the fraction of this subpopulation showed a significant decrease (1.8 ± 0.15 × 10(9)/l [88 ± 1.8%] vs. 2.1 ± 0.12 × 10(9)/l [82 ± 2.8%]). The surface expression of receptors regulating mobilization of neutrophils from bone marrow was decreased (CXCR4 and CD49d on immature neutrophils; CXCR2 on mature neutrophils). The receptor CXCR2 is also involved in the production of reactive oxygen species (ROS), and in line with this, total neutrophils produced less ROS. In addition, following sleep loss, circulating neutrophils exhibited enhanced surface levels of CD11b, which indicates enhanced granular fusion and concomitant protein translocation to the membrane. Our findings demonstrate that sleep loss exerts significant effects on population diversity and function of circulating neutrophils in healthy men. To which extent these changes could explain as to why people with poor sleep patterns are more susceptible to infections warrants further investigation.

Manual-guided cognitive-behavioural therapy for insomnia delivered by ordinary primary care personnel in general medical practice: a randomized controlled effectiveness trial.

Chronic insomnia is a prevalent problem in primary health care and tends to be more serious than insomnia in the general population. These patients often obtain little benefit from hypnotics, and are frequently open to exploring various options for medical treatment. However, most general practitioners (GPs) are unable to provide such options. Several meta-analyses have shown that cognitive-behavioural therapy (CBT) for insomnia results in solid improvements on sleep parameters, and a few studies have demonstrated promising results for nurse-administered CBT in primary care. The aim of this randomized controlled study was to investigate the clinical effectiveness of manual-guided CBT for insomnia delivered by ordinary primary care personnel in general medical practice with unselected patients. Sixty-six primary care patients with insomnia were randomized to CBT or a waiting-list control group. The CBT group improved significantly more than the control group using the Insomnia Severity Index as the outcome. The effect size was high. Sleep diaries showed a significant, medium-sized treatment effect for sleep onset latency and wake time after sleep onset. However, for all measures there is a marked deterioration at follow-up assessments. Almost half of the treated subjects (47%) reported a clinically relevant treatment effect directly after treatment. It is concluded that this way of delivering treatment may be cost-effective.

Acute sleep deprivation has no lasting effects on the human antibody titer response following a novel influenza A H1N1 virus vaccination.

BACKGROUND: Experimental studies in humans have yielded evidence that adaptive immune function, including the production of antigen-specific antibodies, is distinctly impaired when sleep is deprived at the time of first antigen exposure. Here we examined the effects of a regular 24-hour sleep-wake cycle (including 8 hours of nocturnal sleep) and a 24-hour period of continuous wakefulness on the 7-week antibody production in 11 males and 13 females in response to the H1N1 (swine flu) virus vaccination. The specific antibody titer in serum was assayed by the hemagglutination inhibition test on the days 5, 10, 17, and 52 following vaccination. RESULTS: In comparison to the sleep group, sleep-deprived males but not females had reduced serum concentration of H1N1-specific antibodies five days after vaccination, whereas antibody titers at later time points did not differ between the conditions. CONCLUSIONS: These findings concur with the notion that sleep is a supportive influence in the very early stage of an adaptive immune response to a viral antigen. However, our results do not support the view that acute sleep deprivation has lasting effects on the human antibody titer response to influenza vaccination.

Associations Between Fluctuations in Daytime Sleepiness and Motor and Non-Motor Symptoms in Parkinson's Disease.

BACKGROUND: Non-motor fluctuations are a major concern in Parkinson's disease (PD), and they have been categorized into neuropsychiatric, autonomic and sensory fluctuations. However, this categorization does not include sleep and sleep-related features, and the association between daytime sleepiness and other motor and/or non-motor fluctuations in PD remains to be elucidated. OBJECTIVE: To investigate the relationship between daytime sleepiness and other non-motor and motor fluctuations in people with PD. METHODS: A three-day home diary recording daytime sleepiness, mood, anxiety, and motor symptoms was used along with the Karolinska Sleepiness Scale (KSS) and 6 days of accelerometer (Parkinson's KinetiGraph™; PKG™) registration to detect motor fluctuations among people with a DaTSCAN verified clinical PD diagnosis (32 men; mean PD duration, 8.2 years). Participants were categorized as motor fluctuators or non-fluctuators according to the UPDRS part IV and/or the presence of motor and non-motor fluctuations. RESULTS: Fifty-two people with PD participated. Daytime sleepiness correlated significantly with motor symptoms, mood and anxiety among those classified as motor fluctuators (n = 28). Motor fluctuators showed stronger correlations between the individual mean level of all diary variables (daytime sleepiness, anxiety, mood and motor symptoms) when compared to the non-fluctuators (n = 24). Stronger positive within-individual correlations were found among fluctuators in comparison to non-fluctuators. In general, PKG data did not correlate with diary data. CONCLUSION: Episodes of daytime sleepiness, as reported by home diaries, were associated with other self-reported non-motor and motor fluctuations, but were not supported by PKG data.

Is usage of hypnotics associated with mortality?

OBJECTIVE: To investigate the influence of hypnotic usage on all-cause and cause-specific mortality in a middle-aged population. METHODS: A cohort of 1750 men and 1773 women aged 30-65 years who responded to a postal questionnaire in 1983. The questionnaire included questions about hypnotic usage, sleep duration, sleep complaints, medical conditions, depression, demographic and life style variables. Mortality data for the period 1983-2003 were collected. RESULTS: Regular hypnotic usage was reported by 1.7% of men and 2.2% of women, and was associated with short sleep, sleeping difficulties, several health problems and depression. During the 20-year follow-up period 379 men (21.5%) and 278 women (15.5%) died. After adjustment for potential risk factors in multivariate analyses regular hypnotic usage was associated with significantly increased risk of all-cause mortality in men (Hazard ratios [HR], 4.54; 95% confidence interval [CI], 2.47-8.37) and in women 2.03 (95% CI, 1.07-3.86). With regard to cause-specific mortality, regular hypnotic usage in men was a risk factor for coronary artery disease death, cancer death, suicide and death from "all remaining causes." In women it was a risk factor for suicide. CONCLUSIONS: Our results show an increased risk of all-cause mortality and cause-specific mortality in regular users of hypnotics.

A 10-Year Follow-Up of Excessive Daytime Sleepiness in Parkinson's Disease.

INTRODUCTION: The aim of this prospective study was to investigate excessive daytime sleepiness (EDS) over time and in relation to other PD symptoms among people with Parkinson's disease (PD). METHODS: Thirty participants younger than 65 years with PD were randomly selected. At inclusion, mean (SD) disease duration was 6.2 (4.8) years and median (min-max) severity of PD was classified as stage II (stages I-III) according to Hoehn and Yahr. Participants were followed annually for 10 years with clinical assessments of their PD status, medications, comorbidities, and a standardized interview about their sleep habits and occurrence of daytime sleepiness. EDS was assessed by the self-reported Epworth Sleepiness Scale (ESS). Seventeen participants completed the 10-year longitudinal follow-up. RESULTS: Fifteen of 30 persons were classified to suffer from EDS (ESS > 10) at baseline. At the group level, EDS remained stable over 10 years and did not deteriorate in parallel with worsening of motor symptoms. Furthermore, EDS was associated with sleep quality, fatigue, anxiety, depression, and axial/postural/gait impairments. CONCLUSIONS: EDS did not worsen over 10 years, although other PD aspects did. EDS in PD seems to be a complex nonmotor symptom that is unrelated to deterioration of motor symptoms in PD.

Restless legs symptoms with sleepiness in relation to mortality: 20-year follow-up study of a middle-aged Swedish population.

AIM: The aim of the present study was to investigate restless legs symptoms with concomitant daytime sleepiness as a risk factor for mortality in a middle-aged population. METHODS: A cohort of 5102 subjects aged 30-65 years in mid-Sweden who responded to a postal questionnaire in 1983 was followed up. The questionnaire included questions about restless legs symptoms, daytime sleepiness, demographic and lifestyle variables, sleep habits, medical conditions and depression. Mortality data for the period 1983-2003 were collected and death certificates were available for all the 657 responders who died during the follow-up period. RESULTS: Restless legs symptoms with daytime sleepiness was reported by 10.3% and was associated with shorter night sleep time, several health problems and depression. During the follow-up period 379 men (21.6%) and 278 women (15.5%) died. A multivariate model adjusted for age, short night sleep time, lifestyle factors, medical conditions and depression showed that women reporting restless legs symptoms with daytime sleepiness had an excess mortality compared to women without restless legs symptoms and daytime sleepiness (hazard ratios, 1.85; 95% confidence interval, 1.20-2.85; P = 0.005). No influence on mortality risk was found in men reporting restless legs symptoms with daytime sleepiness. CONCLUSIONS: The occurrence of restless legs symptoms with daytime sleepiness in middle-aged women is associated with increased mortality risk.

Restless legs syndrome and its relationship with insomnia symptoms and daytime distress: epidemiological survey in Sweden.

To investigate prevalence estimates of restless legs syndrome (RLS) in relation to insomnia complaints and daytime distress a questionnaire was sent to a randomly selected sample of 1962 inhabitants of Uppsala, Sweden. The questionnaire included questions about sleep and daytime distress and the standardized four-question set for epidemiological settings recommended by the International RLS Study Group. A positive diagnosis of RLS was established in 18.8% of all responders. When the optional question about frequency was applied 5.8% reported frequent symptoms. Insomnia symptoms and daytime distress were significantly associated with the frequency of RLS symptoms.

Sleep patterns in a randomized controlled trial of auricular acupuncture and cognitive behavioral therapy for insomnia.

The aim of the study was to objectively examine how sleep patterns were affected in a short- and long-term perspective after auricular acupuncture (AA) and cognitive behavioral therapy for insomnia (CBT-i). Sixty participants with insomnia disorders (men/women 9/51; mean age of 60.5 years, (SD 9.4)), were randomized to group treatment with AA or CBT-i. Actigraphy recordings were made at baseline, post-treatment and 6-month follow-up. The CBT-i group reduced their time in bed, their actual sleeping time, their sleep latency and their actual time awake. The AA group slept longer, increased their time in bed and decreased their sleep latency post-treatment. The between-groups results differed in wake-up time, rising, time in bed, actual sleep time and actual wake time. The differences were not maintained six months later. In accordance with previous findings the results support the notion that the objective sleep time does not necessarily affect the subjective perception of insomnia.

Learning performance is linked to procedural memory consolidation across both sleep and wakefulness.

We investigated whether learning performance in a procedural finger tapping task before nocturnal sleep would predict performance gains after sleep in 60 young adults. Gains were defined as change in correctly tapped digit sequences between learning (12 trials administered in the evening) and retesting (3 trials administered in the morning after sleep). The same task was also administered to a separate wake group (N = 54 young adults), which learned in the morning and was retested in the evening. Learning performance was determined by either using the average performance on the last three learning trials or the average performance on the best three learning trials. Our results demonstrated an inverse association between learning performance and gains in procedural skill, i.e., good learners exhibited smaller performance gains across both wakefulness and sleep than poor learners. Regardless of learning performance, gains in finger tapping skills were greater after sleep than daytime wakefulness. Importantly, some of our findings were influenced by how learning performance was estimated. Collectively, these results suggest that learning performance and the method through which it is estimated may influence performance gains in finger tapping skills across both sleep and wakefulness.

Can anatomical and functional features in the upper airways predict sleep apnea? A population-based study in females.

CONCLUSION: The importance of clinical findings in the nose and throat, including fiberoptic endoscopy during the Muller maneuver, in predicting sleep apnea is greater in normal-weight than in overweight women. OBJECTIVES: The aim of this study was to identify clinical features that could predict sleep apnea in women. METHOD: From 6817 women who previously answered a questionnaire concerning snoring habits, 230 women who reported habitual snoring and 170 women from the whole cohort went through a full-night polysomnography. A nose and throat examination including fiber endoscopic evaluation of the upper airways during the Muller maneuver was performed in a random selection of 132 women aged 20-70 years. RESULTS: Sleep apnea was defined as an apnea-hypopnea index of > or = 10. The influence of clinical features on the prevalence of sleep apnea varied between normal-weight and overweight women. A low soft palate, retrognathia, the uvula touching the posterior pharyngeal wall in the supine position, and a 75% or more collapse at the soft palate during the Muller maneuver were all significant predictors of sleep apnea in women with a body mass index (BMI) < 25 kg/m2 but not in overweight women.

High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year follow-up study of a middle-aged population.

OBJECTIVE: The aim of this study was to investigate the possible relationship among sleep complaints, sleep duration, and the development of diabetes prospectively over a 12-year period in a middle-aged Swedish population. RESEARCH DESIGN AND METHODS: A random sample of 2,663 subjects aged 45-65 years living in mid-Sweden were sent a postal questionnaire including questions about sleep complaints, sleep duration, sociodemographic characteristics, behavioral risk factors, medical conditions, and depression (response rate 70.2%). Twelve years later, a new questionnaire with almost identical questions was sent to all the survivors (n = 1,604) in 1995, and the questionnaire was answered by 1,244 subjects (77.6%). RESULTS: Men reporting new diabetes at follow-up more often reported short sleep duration (< or =5 h per night) (16.0 vs. 5.9%, P < 0.01), difficulties initiating sleep (16.0 vs. 3.1%, P < 0.001), and difficulties maintaining sleep (28.0 vs. 6.3%, P < 0.001) at baseline than men who did not develop diabetes. Women reporting new diabetes at follow-up reported long sleep duration (> or =9 h per night) more often at baseline than women not developing diabetes (7.9 vs. 2.4%, P < 0.05). In multiple logistic regression models, the relative risk (95% CI) for development of diabetes was higher in men with short sleep duration (2.8 [1.1-7.3]) or difficulties maintaining sleep (4.8 [1.9-12.5]) after adjustment for age and other relevant risk factors. Short or long sleep duration or sleep complaints did not influence the risk of new diabetes in women. CONCLUSIONS: Difficulties maintaining sleep or short sleep duration (< or =5 h) are associated with an increased incidence of diabetes in men.

Delayed sleep phase disorder in a Swedish cohort of adolescents and young adults: Prevalence and associated factors.

A delayed sleep-wake and circadian rhythm often occurs during puberty. While some individuals only develop a delayed sleep phase (DSP), others will fulfill the criteria for the diagnosis of delayed sleep phase disorder (DSPD). All previous studies have however not separated DSP from DSPD, and, as a result, the prevalence and associated factors are largely unknown for the two conditions individually. We estimated the prevalence of DSP and DSPD in a Swedish cohort of adolescents and young adults. We also investigated associated factors in the two conditions relative to each other and individuals with no DSP. A questionnaire regarding sleep patterns, demographics, substance use/abuse and symptoms of depression, anxiety, worry and rumination was sent to 1000 randomly selected participants (16-26 years of age) in Uppsala, Sweden (response rate = 68%). DSP was defined as a late sleep onset and a preferred late wake-up time. The DSPD diagnosis was further operationalized according to the Diagnostic and Statistical Manual of Mental Disorders, Edition 5 (DSM-5) criteria including insomnia or excessive sleepiness, distress or dysfunction caused by the DSP and that the sleep problem had been evident for 3 months. DSP occurred at a frequency of 4.6% and DSPD at a frequency of 4% in the investigated cohort. DSP was more common in males and was associated with not attending educational activity or work, having shift work, nicotine and alcohol use and less rumination. DSPD was equally common in males and females and was associated with not attending educational activity or work and with elevated levels of anxiety. Both DSP and DSPD appear to be common in adolescents and young adults in this Swedish cohort. No educational activity or work was associated with both DSP and DSPD. However, there were also apparent differences between the two groups in shift work, substance use and mental health, relative to persons with no DSP. Thus, it seems reasonable to assess DSP and DSPD as distinct entities in future studies.

Two hours of evening reading on a self-luminous tablet vs. reading a physical book does not alter sleep after daytime bright light exposure.

BACKGROUND: The use of electronic devices emitting blue light during evening hours has been associated with sleep disturbances in humans, possibly due to the blue light-mediated suppression of the sleep-promoting hormone melatonin. However, experimental results have been mixed. The present study therefore sought to investigate if reading on a self-luminous tablet during evening hours would alter sleepiness, melatonin secretion, nocturnal sleep, as well as electroencephalographic power spectral density during early slow-wave sleep. METHODS: Following a constant bright light exposure over 6.5 hours (~569 lux), 14 participants (six females) read a novel either on a tablet or as physical book for two hours (21:00-23:00). Evening concentrations of saliva melatonin were repeatedly measured. Sleep (23:15-07:15) was recorded by polysomnography. Sleepiness was assessed before and after nocturnal sleep. About one week later, experiments were repeated; participants who had read the novel on a tablet in the first experimental session continued reading the same novel in the physical book, and vice versa. RESULTS: There were no differences in sleep parameters and pre-sleep saliva melatonin levels between the tablet reading and physical book reading conditions. CONCLUSIONS: Bright light exposure during daytime has previously been shown to abolish the inhibitory effects of evening light stimulus on melatonin secretion. Our results could therefore suggest that exposure to bright light during the day - as in the present study - may help combat sleep disturbances associated with the evening use of electronic devices emitting blue light. However, this needs to be validated by future studies with larger sample populations.