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1.  Efficacy and hypnotic effects of melatonin in shift-work nurses: double-blind, placebo-controlled crossover trial 
Background
Night work is associated with disturbed sleep and wakefulness, particularly in relation to the night shift. Circadian rhythm sleep disorders are characterized by complaints of insomnia and excessive daytime sleepiness that are primarily due to alterations in the internal circadian timing system or a misalignment between the timing of sleep and the 24-h social and physical environment.
Methods
We evaluated the effect of oral intake of 5 mg melatonin taken 30 minutes before night time sleep on insomnia parameters as well as subjective sleep onset latency, number of awakenings, and duration of sleep. A double-blind, randomized, placebo-controlled crossover study with periods of 1 night and washouts of 4 days comparing melatonin with placebo tablets was conducted. We tried to improve night-time sleep during recovery from night work. Participants were 86 shift-worker nurses aged 24 to 46 years. Each participant completed a questionnaire immediately after awakening.
Results
Sleep onset latency was significantly reduced while subjects were taking melatonin as compared with both placebo and baseline. There was no evidence that melatonin altered total sleep time (as compared with baseline total sleep time). No adverse effects of melatonin were noted during the treatment period.
Conclusion
Melatonin may be an effective treatment for shift workers with difficulty falling asleep.
doi:10.1186/1740-3391-6-10
PMCID: PMC2584099  PMID: 18957133
2.  Sleep Disturbances and Frailty Status in Older Community-Dwelling Men 
Objectives
Test the hypothesis that sleep disturbances are independently associated with greater evidence of frailty in older men.
Design
Cross-sectional analysis of prospective cohort study
Setting
Six U.S. centers
Participants
3133 men ≥67 years
Measurements
Self reported sleep parameters (questionnaire); objective parameters of sleep wake patterns (actigraphy data collected for an average of 5.2 nights); and objective parameters of sleep disordered breathing, nocturnal hypoxemia, and periodic leg movements with arousals (PLMA) (in-home overnight polysomnography). Frailty status classified as robust, intermediate stage or frail using criteria similar to those used in the Cardiovascular Health Study frailty index.
Results
The prevalence of sleep disturbances including poor sleep quality, excessive daytime sleepiness, short sleep duration, reduced sleep efficiency, prolonged sleep latency, sleep fragmentation (greater nighttime wakefulness and frequent long wake episodes), sleep disordered breathing, nocturnal hypoxemia and frequent PLMA was lowest among robust men, intermediate among men in the intermediate stage group, and highest among frail men (p-for-trend ≤0.002 for all sleep parameters). After adjusting for multiple potential confounders, self-reported poor sleep quality (Pittsburgh Sleep Quality Index <5, multivariable odds ratio (MOR) 1.28, 95%CI 1.09–1.50), sleep efficiency <70% (MOR 1.37, 95% CI 1.12–1.67), sleep latency ≥60 minutes (MOR 1.42, 95% CI 1.10–1.82), and sleep disordered breathing (respiratory disturbance index ≥15, MOR 1.38, 95% CI 1.15–1.65) were each independently associated with an increased odds of greater frailty status.
Conclusion
Sleep disturbances including poor self-reported sleep quality, reduced sleep efficiency, prolonged sleep latency and sleep disordered breathing are independently associated with greater evidence of frailty.
doi:10.1111/j.1532-5415.2009.02490.x
PMCID: PMC3024909  PMID: 19793160
sleep disturbances; frailty; aging
3.  A comparison of idiopathic hypersomnia and narcolepsy-cataplexy using self report measures and sleep diary data. 
Eighteen patients with idiopathic hypersomnia (IH) were compared with 50 patients with the narcoleptic syndrome of cataplexy and daytime sleepiness (NLS) using self report questionnaires and a diary of sleep/wake patterns. The IH group reported more consolidated nocturnal sleep, a lower propensity to nap, greater refreshment after naps, and a greater improvement in excessive daytime sleepiness since onset than the NLS group. In IH, the onset of excessive daytime sleepiness was predominantly associated with familial inheritance or a viral illness. Two variable--number of reported awakenings during nocturnal sleep and the reported change in sleepiness since onset--provided maximum discrimination between the IH and NLS groups. Confusional arousals, extended naps or nocturnal sleep, autonomic nervous system dysfunction, low ratings of medication effectiveness, or side effects of medication were not associated differentially with either IH or NLS.
PMCID: PMC486375  PMID: 8778267
4.  Actual and Perceived Sleep: Associations with Daytime Functioning among Postpartum Women 
Physiology & behavior  2010;102(2):234-238.
Sleep and wake have a homeostatic relation that influences most aspects of physiology and waking behavior. Sleep disturbance has a detrimental effect on sleepiness and psychomotor vigilance. The purpose of this study was to identify which actual or perceived sleep characteristics accounted for the most variance in daytime functioning among postpartum mothers. Seventy first-time postpartum mothers' actual sleep (actigraphically estimated: total sleep time, number of wake bouts, length of nocturnal wake, and sleep efficiency) and perceived sleep (self-reported: number of awakenings, wake time, and sleep quality) was measured along with their daytime functioning (Stanford Sleepiness Scale [SSS], Epworth Sleepiness Scale [ESS], Visual Analogue of Fatigue Scale [VAFS], and morning Psychomotor Vigilance Test [PVT]). Data were repeatedly collected from the same sample during postpartum weeks 2, 7, and 13. Four stepwise linear regressions were calculated for each postpartum week to examine which objective and/or subjective variable(s) accounted for the most variance in daytime functioning. The SSS and VAFS were both most consistently associated with perceived sleep quality. The ESS was most consistently associated with actual total sleep time. PVT performance was most consistently associated with estimates of actual and perceived sleep efficiency. Actual and perceived sleep profiles were differentially associated with specific daytime functions. These results from postpartum mothers may indicate that populations who experience specific forms of sleep disturbance (e.g. fragmentation, deprivation) may also experience specific daytime conditions.
doi:10.1016/j.physbeh.2010.11.017
PMCID: PMC3010463  PMID: 21095200
Actual; actigraphy; subjective; objective; perceived; sleep; sleepiness; fatigue; performance; behavior; postpartum; maternal
5.  Sleep architecture and sleep-related mentation in securely and insecurely attached people 
Attachment & human development  2011;13(2):141-154.
Based on REM sleep’s brain activation patterns and its participation in consolidation of emotional memories, we tested the hypothesis that measures of REM sleep architecture and REM sleep-related mentation would be associated with attachment orientation. After a habituation night in a sleep lab, a convenience sample of 64 healthy volunteers were awakened 10 minutes into a REM sleep episode and 10 minutes into a control NREM sleep episode in counterbalanced order, then asked to report a dream and to rate themselves and a significant other on a list of trait adjectives. Relative to participants classified as having secure attachment orientations, participants classified as anxious took less time to enter REM sleep and had a higher frequency of REM dreams with aggression and self-denigrating themes. There were no significant differences across attachment groups in other measures of sleep architecture or in post REM-sleep awakening ratings on PANAS subscales reflecting mood and alertness. Selected aspects of REM sleep architecture and mentation appeared to be associated with attachment orientation. We suggest that REM sleep plays a role in processing experiences and emotions related to attachment, and that certain features of sleep and dreaming reflect attachment orientations.
doi:10.1080/14616734.2011.553999
PMCID: PMC3060050  PMID: 21390907
REM sleep; NREM sleep; REM latency; attachment status; dreams; mood
6.  DQB1*0602 predicts interindividual differences in physiologic sleep, sleepiness, and fatigue 
Neurology  2010;75(17):1509-1519.
Objective:
The human leukocyte antigen (HLA) DQB1*0602 allele is closely associated with narcolepsy, a neurologic disorder characterized by excessive daytime sleepiness, fragmented sleep, and shortened REM sleep latency. We evaluated whether DQB1*0602 was a novel marker of interindividual differences by determining its relationship to sleep homeostatic, sleepiness, and cognitive responses to baseline and chronic partial sleep deprivation (PSD) conditions.
Methods:
Ninety-two DQB1*0602-negative and 37 DQB1*0602-positive healthy adults participated in a protocol of 2 baseline 10 hours time in bed (TIB) nights followed by 5 consecutive 4 hours TIB nights. DQB1*0602 allelic frequencies did not differ significantly between Caucasians and African Americans.
Results:
During baseline, although DQB1*0602-positive subjects were subjectively sleepier and more fatigued, they showed greater sleep fragmentation, and decreased sleep homeostatic pressure and differentially sharper declines during the night (measured by non-REM EEG slow-wave energy [SWE]). During PSD, DQB1*0602-positive subjects were sleepier and showed more fragmented sleep, despite SWE elevation comparable to negative subjects. Moreover, they showed differentially greater REM sleep latency reductions and smaller stage 2 reductions, along with differentially greater increases in fatigue. Both groups demonstrated comparable cumulative decreases in cognitive performance.
Conclusions:
DQB1*0602 positivity in a healthy population may represent a continuum of some sleep–wake features of narcolepsy. DQB1*0602 was associated with interindividual differences in sleep homeostasis, physiologic sleep, sleepiness, and fatigue—but not in cognitive measures—during baseline and chronic PSD. Thus, DQB1*0602 may represent a genetic biomarker for predicting such individual differences in basal and sleep loss conditions.
GLOSSARY
= analysis of variance;
= Controlled Oral Word Association Test;
= Digit Span;
= Digit Symbol Substitution Task;
= human leukocyte antigen;
= Karolinska Sleepiness Scale;
= Maintenance of Wakefulness Test;
= Profile of Mood States;
= partial sleep deprivation;
= polysomnography;
= Psychomotor Vigilance Task;
= sleep onset latency;
= sleep deprivation/restriction;
= slow-wave activity;
= slow-wave energy;
= time in bed;
= Tower of London;
= total sleep deprivation;
= visual analog scale;
= wake after sleep onset.
doi:10.1212/WNL.0b013e3181f9615d
PMCID: PMC2974463  PMID: 20975052
7.  Gender difference in the effect of daytime sleep on declarative memory for pictures*  
Objective: To investigate gender difference in the effects of daytime sleep on item and source memories, which are dissociable elements of declarative memory, and the effects of sleep on recollection and familiarity, which are two processes underlying recognition. Methods: Participants saw a series of pictures with either blue or red background, and were then given a pretest for item and source memories. Then males and females respectively were randomly assigned either to a wake or a sleep condition. In the wake condition, participants remained awake until the posttest; in the sleep condition, participants slept for 1 h until awakened and asked to remain awake until the posttest. Results: Daytime sleep contributed to retention of source memory rather than item memory in females, whereas males undergoing daytime sleep had a trend towards increased familiarity. For females, however, neither recollection nor familiarity appeared to be influenced by daytime sleep. Conclusion: The mechanism underlying gender difference may be linked with different memory traces resulting from different encoding strategies, as well as with different electrophysiological changes during daytime sleep.
doi:10.1631/jzus.B0820384
PMCID: PMC2704972  PMID: 19585672
Gender difference; Declarative memory; Recollection; Familiarity; Daytime sleep
8.  A Longitudinal Study of Depression, Pain, and Stress as Predictors of Sleep Disturbance among Women with Metastatic Breast Cancer 
Biological psychology  2006;75(1):37-44.
Objective
Sleep disturbances are common among women with breast cancer and can have serious consequences. The present study examined depression, pain, life stress, and participation in group therapy in relation to sleep disturbances in a sample of women with metastatic breast cancer.
Methods
Ninety-three women with metastatic breast cancer participated in a large intervention trial examining the effect of the group therapy on their symptoms. They completed measures of depression, pain, life stress, and sleep disturbance at baseline, 4, 8 and 12 months.
Results
The results showed that higher initial levels of depression at baseline predicted problems associated with getting up in the morning, waking up during the night, and daytime sleepiness. Increases in depression over the course of 12 months were associated with fewer hours of sleep, more problems with waking up during the night and more daytime sleepiness. Higher levels of pain at baseline predicted more problems getting to sleep. Increases in pain predicted more difficulty getting to sleep and more problems waking up during the night. Greater life stress at baseline predicted more problems getting to sleep and more daytime sleepiness.
Conclusions
Depression, pain, and life stress scores were each associated with different types of negative change in self-reported sleep disturbances. Depression, especially worsening depression, was associated with the greatest number of types of negative change. The relationships found between sleep disturbance and depression, pain, and life stress suggest specific ways to address the problem of sleep disturbance for women with metastatic breast cancer and show how different types of disturbed sleep may be clinical markers for depression, pain, or life stress in this population.
doi:10.1016/j.biopsycho.2006.11.002
PMCID: PMC1894689  PMID: 17166646
sleep disturbance; metastatic breast cancer; pain; depression; stressful life events
9.  Disease and Degeneration of Aging Neural Systems that Integrate Sleep Drive and Circadian Oscillations 
Sleep/wake and circadian rest-activity rhythms become irregular with age. Typical outcomes include fragmented sleep during the night, advanced sleep phase syndrome and increased daytime sleepiness. These changes lead to a reduction in the quality of life due to cognitive impairments and emotional stress. More importantly, severely disrupted sleep and circadian rhythms have been associated with an increase in disease susceptibility. Additionally, many of the same brain areas affected by neurodegenerative diseases include the sleep and wake promoting systems. Any advances in our knowledge of these sleep/wake and circadian networks are necessary to target neural areas or connections for therapy. This review will discuss research that uses molecular, behavioral, genetic and anatomical methods to further our understanding of the interaction of these systems.
doi:10.3389/fneur.2011.00066
PMCID: PMC3199684  PMID: 22028699
aging; neurodegenerative; sleep; wake; circadian; disease
10.  The impact of a week of simulated night work on sleep, circadian phase, and performance 
Methods: Fifteen healthy subjects participated in an adaptation and baseline night sleep, directly followed by seven simulated eight-hour night shifts (2300 to 0700 hours). At the end of each shift they were taken outside and exposed to natural light for 20 minutes. They then slept from approximately 0800 hours until they naturally awoke.
Results: There was a significant increase in mean performance on a visual psychomotor vigilance task across the week. Daytime sleep quality and quantity were not negatively affected. Total sleep time (TST) for each of the daytime sleeps was reduced, resulting in an average cumulative sleep debt of 3.53 hours prior to the final night shift. TST for each of the daytime sleep periods did not significantly differ from the baseline night, nor did TST significantly vary across the week. There was a significant decrease in wake time after sleep onset and sleep onset latency across the week; sleep efficiency showed a trend towards greater efficiency across the consecutive daytime sleeps. Hours of wakefulness prior to each simulated night shift significantly varied across the week. The melatonin profile significantly shifted across the week.
Conclusions: Results suggest that under optimal conditions, the sleep debt that accumulates during consecutive night shifts is relatively small and does not exacerbate decrements in night-time performance resulting from other factors. When sleep loss is minimised, adaptation of performance during consecutive night shifts can occur in conjunction with circadian adaptation.
doi:10.1136/oem.60.11.e13
PMCID: PMC1740426  PMID: 14573724
11.  The Impact of Moderate Sleep Loss on Neurophysiologic Signals during Working-Memory Task Performance 
Sleep  2002;25(7):784-794.
Study Objectives
This study examined how sleep loss affects neurophysiologic signals related to attention and working memory.
Design
Subjective sleepiness, resting-state electroencephalogram, and behavior and electroencephalogram during performance of working-memory tasks were recorded in a within-subject, repeated-measures design.
Setting
Data collection occurred in a computerized laboratory setting.
Participants
Sixteen healthy adults (mean age, 26 years; 8 female)
Interventions
Data from alert daytime baseline tests were compared with data from tests during a late-night, extended-wakefulness session that spanned up to 21 hours of sleep deprivation.
Measurements and Results
Alertness measured both subjectively and electrophysiologically decreased monotonically with increasing sleep deprivation. A lack of alertness-related changes in electroencephalographic measures of the overall mental effort exerted during task execution indicated that participants attempted to maintain high levels of performance throughout the late-night tests. Despite such continued effort, responses became slower, more variable, and more error prone within 1 hour after participants' normal time of sleep onset. This behavior failure was accompanied by significant degradation of event-related brain potentials related to the transient focusing of attention.
Conclusions
Moderate sleep loss compromises the function of neural circuits critical to subsecond attention allocation during working-memory tasks, even when an effort is made to maintain wakefulness and performance. Multivariate analyses indicate that combinations of working-memory-related behavior and neurophysiologic measures can be sensitive enough to permit reliable detection of such effects of sleep loss in individuals. Similar methods might prove useful for assessment of functional alertness in patients with sleep disorders.
PMCID: PMC1626388  PMID: 12405615
Fatigue; alertness; cognition; attention; working memory; electroencephalogram; event-related potentials
12.  Sleep and Daytime Functioning: A Short-term Longitudinal Study of Three Preschool-age Comparison Groups 
This study examined sleep, sleepiness, and daytime performance in 68 children with autism, 57 children with intellectual disability (ID), and 69 typically developing preschool children. Children in the autism and ID groups had poorer daytime performance and behaviors than the typically developing children. Children in the ID group also were significantly sleepier than children in both the autism and typically developing groups. These significant differences persisted over 6 months. Actigraph-defined sleep behaviors and problems did not relate to daytime sleepiness or daytime performance and behaviors for the children with autism or the typically developing group. For the ID group, longer night awakenings and lower sleep efficiency predicted more daytime sleepiness. For each group, parent-report sleep problems were associated with more daytime sleepiness and more behavior problems.
doi:10.1352/1944-7558-117.4.275
PMCID: PMC3500838  PMID: 22809074
autism; intellectual disability; behavior; sleep
13.  Prevalence, Patterns, and Persistence of Sleep Problems in the First 3 Years of Life 
Pediatrics  2012;129(2):e276-e284.
OBJECTIVE:
Examine the prevalence, patterns, and persistence of parent-reported sleep problems during the first 3 years of life.
METHODS:
Three hundred fifty-nine mother/child pairs participated in a prospective birth cohort study. Sleep questionnaires were administered to mothers when children were 6, 12, 24, and 36 months old. Sleep variables included parent response to a nonspecific query about the presence/absence of a sleep problem and 8 specific sleep outcome domains: sleep onset latency, sleep maintenance, 24-hour sleep duration, daytime sleep/naps, sleep location, restlessness/vocalization, nightmares/night terrors, and snoring.
RESULTS:
Prevalence of a parent-reported sleep problem was 10% at all assessment intervals. Night wakings and shorter sleep duration were associated with a parent-reported sleep problem during infancy and early toddlerhood (6–24 months), whereas nightmares and restless sleep emerged as associations with report of a sleep problem in later developmental periods (24–36 months). Prolonged sleep latency was associated with parent report of a sleep problem throughout the study period. In contrast, napping, sleep location, and snoring were not associated with parent-reported sleep problems. Twenty-one percent of children with sleep problems in infancy (compared with 6% of those without) had sleep problems in the third year of life.
CONCLUSIONS:
Ten percent of children are reported to have a sleep problem at any given point during early childhood, and these problems persist in a significant minority of children throughout early development. Parent response to a single-item nonspecific sleep query may overlook relevant sleep behaviors and symptoms associated with clinical morbidity.
doi:10.1542/peds.2011-0372
PMCID: PMC3357046  PMID: 22218837
sleep problems; infants; toddlers; prevalence; persistence
14.  Unfair Treatment is associated with Poor Sleep in African American and Caucasian Adults: Pittsburgh SleepSCORE Project 
Objective
To test the association between self-reported unfair treatment and objective and self-reported sleep characteristics in African American and Caucasian adults.
Design
Cross-sectional study of 97 African American and 113 Caucasian middle-aged adults.
Main Outcome Measures
Participants completed: a) two night in-home, polysomnography (PSG) sleep study, b) sleep diaries and actigraph assessments across nine days and nights, and c) self-report measures of sleep quality in the past month, and daytime sleepiness in the past two weeks.
Results
Greater unfair treatment was associated with reports of poorer self-reported sleep quality and greater daytime sleepiness, shorter sleep duration and lower sleep efficiency as measured by actigraphy and PSG, and a smaller proportion of rapid eye movement (REM) sleep. Racial/ethnic differences were few. Exploratory analyses showed that nightly worry partially mediated the associations of unfair treatment with sleep quality, daytime sleepiness, sleep efficiency (actigraphy), and proportion of REM sleep.
Conclusion
Perceptions of unfair treatment are associated with sleep disturbances in both African American and Caucasian adults. Future studies are needed to identify the pathways that account for the association between unfair treatment and sleep.
doi:10.1037/a0022976
PMCID: PMC3131074  PMID: 21553979
unfair treatment; discrimination; sleep disturbance; worry; race/ethnicity
15.  Sleep Insufficiency, Sleep Health Problems and Performance in High School Students 
A survey on sleep schedule, sleep health, school performance and school start times was conducted in 1,941 adolescents. A high level of early and circadian-disadvantaged sleep/wake schedules during weekdays was observed. Shorter sleep duration on weekdays was reported, especially in upper classmen. Complaints of inadequate sleep and sleepiness during weekdays, alarm clock use, and napping were prevalent. Night awakening and prolonged sleep onset were common and associated with poor school performance. Students with a sleep length of less than 7 hours on both weekdays and weekends exhibited poorer performance, while those who made up this sleep loss on weekends did not. The total number of poor sleep factors in an individual also correlated with poor school performance. Earlier school start times were associated with a perception of poor sleep quality, shorter sleep duration and more sleep health problems. We conclude that sleep inadequacies and sleep health problems were prevalent in this population, especially in those who started school earlier in the morning, and that these poor sleep factors were associated with school performance.
doi:10.4137/CCRPM.S7955
PMCID: PMC3212860  PMID: 22084618
sleep deprivation; sleep health problem; adolescents; performance; school start time
16.  How Aging Affects Sleep-Dependent Memory Consolidation? 
Memories are not stored as they were initially encoded but rather undergo a gradual reorganization process, termed memory consolidation. Numerous data indicate that sleep plays a major role in this process, notably due to the specific neurochemical environment and the electrophysiological activity observed during the night. Two putative, probably not exclusive, models (“hippocampo-neocortical dialogue” and “synaptic homeostasis hypothesis”) have been proposed to explain the beneficial effect of sleep on memory processes. However, all data gathered until now emerged from studies conducted in young subjects. The investigation of the relationships between sleep and memory in older adults has sparked off little interest until recently. Though, aging is characterized by memory impairment, changes in sleep architecture, as well as brain and neurochemical alterations. All these elements suggest that sleep-dependent memory consolidation may be impaired or occurs differently in older adults. This review outlines the mechanisms governing sleep-dependent memory consolidation, and the crucial points of this complex process that may dysfunction and result in impaired memory consolidation in aging.
doi:10.3389/fneur.2012.00008
PMCID: PMC3270392  PMID: 22347209
sleep; memory consolidation; aging; episodic memory; procedural memory; slow wave sleep, hippocampus
17.  Increased cerebral blood flow in the right frontal lobe area during sleep precedes self-awakening in humans 
BMC Neuroscience  2012;13:153.
Background
Some people can subconsciously wake up naturally (self-awakening) at a desired/planned time without external time stimuli. However, the underlying mechanism regulating this ability remains to be elucidated. This study sought to examine the relationship between hemodynamic changes in oxyhemoglobin (oxy-Hb) level in the prefrontal cortex and sleep structures during sleep in subjects instructed to self-awaken.
Results
Fifteen healthy right-handed male volunteers with regular sleep habits participated in a consecutive two-night crossover study. The subjects were instructed to wake up at a specified time (“request” condition) or instructed to sleep until the morning but forced to wake up at 03:00 without prior notice (“surprise” condition). Those who awoke within ± 30 min of the planned waking time were defined as those who succeeded in self-awakening (“success” group). Seven subjects succeeded in self-awakening and eight failed.
No significant differences were observed in the amounts of sleep in each stage between conditions or between groups. On the “request” night, an increase in oxy-Hb level in the right prefrontal cortex and a decrease in δ power were observed in the “success” group around 30 min before self-awakening, whereas no such changes were observed in the “failure” group. On the “surprise” night, no significant changes were observed in oxy-Hb level or δ power in either group.
Conclusions
These findings demonstrate a correlation between self-awakening and a pre-awakening increase in hemodynamic activation in the right prefrontal cortex, suggesting the structure’s contribution to time estimation ability.
doi:10.1186/1471-2202-13-153
PMCID: PMC3538054  PMID: 23256572
Time estimation ability; Self-awakening; Sleep; Cognitive science; Prefrontal cortex; Insomnia
18.  The relationship between sleep and wake habits and academic performance in medical students: a cross-sectional study 
BMC Medical Education  2012;12:61.
Background
The relationship between the sleep/wake habits and the academic performance of medical students is insufficiently addressed in the literature. This study aimed to assess the relationship between sleep habits and sleep duration with academic performance in medical students.
Methods
This study was conducted between December 2009 and January 2010 at the College of Medicine, King Saud University, and included a systematic random sample of healthy medical students in the first (L1), second (L2) and third (L3) academic levels. A self-administered questionnaire was distributed to assess demographics, sleep/wake schedule, sleep habits, and sleep duration. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). School performance was stratified as “excellent” (GPA ≥3.75/5) or “average” (GPA <3.75/5).
Results
The final analysis included 410 students (males: 67%). One hundred fifteen students (28%) had “excellent” performance, and 295 students (72%) had “average” performance. The “average” group had a higher ESS score and a higher percentage of students who felt sleepy during class. In contrast, the “excellent” group had an earlier bedtime and increased TST during weekdays. Subjective feeling of obtaining sufficient sleep and non-smoking were the only independent predictors of “excellent” performance.
Conclusion
Decreased nocturnal sleep time, late bedtimes during weekdays and weekends and increased daytime sleepiness are negatively associated with academic performance in medical students.
doi:10.1186/1472-6920-12-61
PMCID: PMC3419622  PMID: 22853649
Sleep; Sleep duration; Medical students; Academic performance; School
19.  Overnight Changes of Immune Parameters and Catecholamines Are Associated With Mood and Stress 
Psychosomatic Medicine  2010;72(8):755-762.
Objectives
To test the hypothesis that a nocturnal decrease of secretion of inflammation markers and catecholamines would be associated with mood and stress variables even after controlling for objective sleep variables.
Methods
A total of 130 healthy volunteers participated in this study, spending 2 nights in the Gillin Laboratory of Sleep and Chronobiology at the University of California, San Diego, General Clinical Research Center. Blood samples were obtained before sleep (10:30 PM) and after awakening (6:30 AM) on the first day, and these samples were assayed for inflammatory biomarkers and catecholamines. On the second night, polysomnographic records were scored for objective sleep variables, e.g., total sleep time and wake after sleep onset. Self-rating scales for mood, stress, depression, and daily hassles were administered the second day.
Results
The nocturnal decrease in interleukin-6 was smaller in people who reported more negative mood or fatigue and greater in those who reported more uplift events (e.g., with Profile of Mood States fatigue rp = −.25 to −.30). People with high stress or high depression levels had smaller nocturnal decreases of epinephrine. That relationship was even stronger when partial correlations were used to control for morning level and sleep variables. The associations between nocturnal changes of C-reactive protein, soluble tumor necrosis factor-receptor I, and norepinephrine with psychological states were nonremarkable.
Conclusions
The analyses of nocturnal change scores (difference scores) add substantial information compared with the traditional analyses of morning levels of immune variables and catecholamines alone. Subjective well-being is significantly associated with a greater nocturnal decrease of interleukin-6 and epinephrine. More research on nocturnal adaptation processes is warranted.
doi:10.1097/PSY.0b013e3181f367e2
PMCID: PMC3162345  PMID: 20841563
sleep; stress; mood; cytokines; sympathetic nervous system; chronobiology
20.  APPROACHES TO THE ASSESSMENT OF AROUSALS AND SLEEP DISTURBANCE IN CHILDREN 
Sleep medicine  2010;11(7):622-627.
Childhood arousals, awakenings, and sleep disturbances during the night are common problems for both patients and their families. Additionally, inadequate sleep may contribute to daytime sleepiness, behavioral problems, and other important consequences of pediatric sleep disorders. Arousals, awakenings, and sleep disturbances can be quantified by routine polysomnography, and arousal scoring is generally performed as part of the standard polysomnogram. Here we review current approaches to quantification of arousals and sleep disturbances and examine outcomes that have been associated with these measures. Initial data suggest that computer-assisted identification of nonvisible arousals, cyclic alternating patterns, or respiratory cycle-related EEG changes may complement what can be accomplished by human scorers. Focus on contiguous bouts of sleep or specific sleep stages may prove similarly useful. Incorporation of autonomic arousal measures—such as heart rate variability, pulse transit time, or peripheral arterial tone—into standard reports may additionally capture subtle sleep fragmentation.
doi:10.1016/j.sleep.2009.11.018
PMCID: PMC2966941  PMID: 20620104
child; pediatric; sleep; arousals; sleep disturbance; spectral analysis; respiratory cycle related EEG changes; RCREC; heart rate variability; pulse transit time; peripheral arterial tonometry; movements
21.  The Role of Sleep in False Memory Formation 
Memories are not stored as exact copies of our experiences. As a result, remembering is subject not only to memory failure, but to inaccuracies and distortions as well. Although such distortions are often retained or even enhanced over time, sleep’s contribution to the development of false memories is unknown. Here, we report that a night of sleep increases both veridical and false recall in the Deese-Roediger-McDermott (DRM) paradigm, compared to an equivalent period of daytime wakefulness. But while veridical memory deteriorates across both wake and sleep, false memories are preferentially preserved by sleep, actually showing a non-significant improvement. The same selectivity of false over veridical memories was observed in a follow-up nap study. Unlike previous studies implicating deep, slow-wave sleep (SWS) in declarative memory consolidation, here veridical recall correlated with decreased SWS, a finding that was observed in both the overnight and nap studies. These findings lead to two counterintuitive conclusions – that under certain circumstances sleep can promote false memories over veridical ones, and SWS can be associated with impairment rather than facilitation of declarative memory consolidation. While these effects produce memories that are less accurate after sleep, these memories may, in the end, be more useful.
doi:10.1016/j.nlm.2009.03.007
PMCID: PMC2789473  PMID: 19348959
22.  Motor sequence consolidation: constrained by critical time windows or competing components 
Skill improvements may develop between practice sessions during memory consolidation. Skill enhancement within an egocentric coordinate frame develops over wake, whereas skill enhancement in an allocentric coordinate frame develops over a night of sleep. We tested whether both types of improvement could develop over two different 24-hr intervals: 8am to 8am or from 8pm to 8pm. We found that for each 24 hour interval, only one type of skill improvement was seen. Despite passing through wake and a night of sleep participants only showed skill improvements commensurate with either a night of sleep or a day awake. The nature of the off-line skill enhancement was determined by when consolidation occurred within the normal sleep-wake cycle. We conclude that motor sequence consolidation is constrained either by having critical time windows or by a competitive interaction in which improvements within one coordinate frame actively block improvements from developing in the alternative coordinate frame.
doi:10.1007/s00221-006-0701-6
PMCID: PMC1805458  PMID: 17021894
23.  Armodafinil for Treatment of Excessive Sleepiness Associated With Shift Work Disorder: A Randomized Controlled Study 
Mayo Clinic Proceedings  2009;84(11):958-972.
OBJECTIVE: To assess the effect of armodafinil, 150 mg, on the physiologic propensity for sleep and cognitive performance during usual night shift hours in patients with excessive sleepiness associated with chronic (≥3 months) shift work disorder (SWD) of moderate or greater severity.
PATIENTS AND METHODS: This 12-week, randomized controlled study was conducted at 42 sleep research facilities in North America from April 2 through December 23, 2004, and enrolled 254 permanent or rotating night shift workers with SWD. Entry criteria included excessive sleepiness during usual night shifts for 3 months or longer (corroborated by mean sleep latency of ≤6 minutes on a Multiple Sleep Latency Test), insomnia (sleep efficiency ≤87.5% during daytime sleep), and SWD that was judged clinically to be of moderate or greater severity. Patients received armodafinil, 150 mg, or placebo 30 to 60 minutes before each night shift. Physiologic sleep propensity during night shift hours, clinical impression of severity, patient-reported sleepiness, and cognitive function were assessed during laboratory night shifts at weeks 4, 8, and 12.
RESULTS: Armodafinil significantly improved mean (SD) sleep latency from 2.3 (1.6) minutes at baseline to 5.3 (5.0) minutes at final visit, compared with a change from 2.4 (1.6) minutes to 2.8 (2.9) minutes in the placebo group (P<.001). Clinical condition ratings improved in more patients receiving armodafinil (79%) vs placebo (59%) (P=.001). As reported by patients' diaries, armodafinil significantly reduced sleepiness during laboratory nights (P<.001), night shifts at work (P<.001), and the commute home (P=.003). Armodafinil improved performance on standardized memory (P<.001) and attention (power, P=.001; continuity, P<.001) tests compared with placebo. Armodafinil was well tolerated and did not affect daytime sleep, as measured by polysomnography.
CONCLUSION: In patients with excessive sleepiness associated with chronic SWD of moderate or greater severity, armodafinil significantly improved wakefulness during scheduled night work, raising mean nighttime sleep latency above the level considered to indicate severe sleepiness during the daytime. Armodafinil also significantly improved measures of overall clinical condition, long-term memory, and attention.
Trial Registration: clinicaltrials.gov Identifier: NCT00080288
In patients with excessive sleepiness associated with chronic shift work disorder of moderate or greater severity, armodafinil significantly improved wakefulness during scheduled night work, raising mean nighttime sleep latency above the level considered to indicate severe sleepiness during the daytime. Armodafinil also significantly improved measures of overall clinical condition, long-term memory, and attention.
PMCID: PMC2770907  PMID: 19880686
24.  Effects on subjective and objective alertness and sleep in response to evening light exposure in older subjects 
Behavioural brain research  2011;224(2):272-278.
Evening bright light exposure is reported to ameliorate daytime sleepiness and age-related sleep complaints, and also delays the timing of circadian rhythms. We tested whether evening light exposure given to older adults with sleep-wake complaints would delay the timing of their circadian rhythms with respect to their sleep timing, thereby reducing evening sleepiness and improving subsequent sleep quality. We examined the impact of evening light exposure from two different light sources on subjective alertness, EEG activity during wakefulness, and sleep stages.
Ten healthy older adults with sleep complaints (mean age=63.3 yrs; 6F) participated in a 13-day study. After three baseline days, circadian phase was assessed. On the evening of days 5–8 the subjects were exposed for 2 h to either polychromatic blue-enriched white light or standard white fluorescent light, and on the following day circadian phase was re-assessed. Subjects were allowed to leave the laboratory during all but the two days when the circadian phase assessment took place. Evening assessments of subjective alertness, and wake and sleep EEG data were analyzed.
Subjective alertness and wake EEG activity in the alpha range (9.75–11.25 Hz) were significantly higher during light exposures when compared to the pre-light exposure evening (p<0.05). The light exposures produced circadian phase shifts and significantly prolonged latency to rapid eye-movement (REM) sleep for both light groups (p<0.05). The increase in wake EEG alpha activity during the light exposures was negatively correlated with REM sleep duration (p<0.05).
Evening light exposure could benefit older adults with early evening sleepiness, without negatively impacting the subsequent sleep episode.
doi:10.1016/j.bbr.2011.05.029
PMCID: PMC3169848  PMID: 21664380
sleep; circadian; aging; light exposure
25.  Effects of submental stimulation for several consecutive nights in patients with obstructive sleep apnoea. 
Thorax  1994;49(5):446-452.
BACKGROUND--It has previously been reported that short term submental stimulation can reduce the frequency of apnoea and improve sleep architecture in patients with obstructive sleep apnoea. The effects of submental stimulation during consecutive nights on apnoea or on daytime sleepiness have not, however, been studied. METHODS--Patients with obstructive sleep apnoea were studied by polysomnography on a control night, for five consecutive nights of submental stimulation, and on three following nights (n = 8). A multiple sleep latency test (MSLT) (n = 8) and measurement of the upper airway resistance (n = 5) were performed during the day after the polysomnographic study, on the control night, and on the fifth stimulation night. In an additional five patients with obstructive sleep apnoea, matched for age, sex, and weight, the effects of two nights of stimulation were examined for comparison. Submental stimulation began when an apnoea lasted for five seconds and stopped with the resumption of breathing as detected by oronasal flow. RESULTS--The apnoea index, the number of times per hour that SaO2 dropped below 85% (SaO2 < 85%/hour), and the total apnoea duration expressed as a percentage of total sleep time during stimulation nights decreased to approximately 50% of the corresponding values on the control night. This improvement persisted for at least two nights after the five consecutive stimulation nights, but not after the two consecutive stimulation nights. Sleep architecture and MSLT following the stimulation nights improved but upper airway resistance did not change. CONCLUSIONS--Submental stimulation for five consecutive nights in patients with obstructive sleep apnoea improved the breathing disturbance, sleep quality, and daytime sleepiness. The effect lasted for the following two nights, but did not completely abolish the sleep disordered breathing.
PMCID: PMC474864  PMID: 8016764

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