Journal SLEEP Articles

Towards an Improved Neuropsychology of Poor Sleep?
Commentary on Edinger JD, Means MK, Carney CE, Krystal AD. Psychomotor Performance Deficits and Their Relation to Prior Nights’ Sleep Among Individuals with Primary Insomnia. Sleep 2008;31:599-607.

COMMENTARY - Towards an Improved Neuropsychology of Poor Sleep?

Increasing Sleep Duration for a Healthier (and Less Obese?) Population Tomorrow
Commentary on Cappuccio FP, Taggart FM, Kandala N-B, et al. Meta-analysis of short sleep duration and obesity in
children and adults. Sleep 2008;31:619-626.

COMMENTARY - Increasing Sleep Duration for a Healthier (and Less Obese?) Population Tomorrow

Too Weighty a Link Between Short Sleep and Obesity?

LETTER TO THE EDITOR - Too Weighty a Link Between Short Sleep and Obesity?

Psychomotor Performance Deficits and Their Relation to Prior Nights’ Sleep Among Individuals with Primary Insomnia

Objective:

To examine psychomotor (reaction time) performance deficits and their relation to subjective and objective sleep measures among individuals with primary insomnia (PI).

Design and Setting:

This study was conducted at affiliated VA and academic medical centers using a matched-groups, cross-sectional research design.
Participants: Seventy-nine (43 women) individuals with PI (MAge = 50.0 ± 17.1 y) and 84 (41 women) well-screened normal sleepers (MAge = 48.6 ± 16.8 y).

Methods and Measures:

Participants underwent 3 nights of polysomnography (PSG) followed by daytime testing with a 4-trial multiple sleep latency test (MSLT). Before each MSLT nap, they rated their sleepiness and completed a performance battery that included simple reaction time (SRT), continuous performance (CPT), and 4 switching attention (SAT) tests. Performance measures included the mean response latency and the standard deviation of each subject’s within-test response latencies.

Results:

PI sufferers reported greater (P = 0.001) daytime sleepiness, but were significantly (P = 0.02), more alert than normal sleepers on the MSLT. Multivariate analyses showed the PI group had significantly longer response latencies and greater response variability across many of the subtests than did the controls. Regression analyses showed that both PSG- and diary-based sleep measures contributed to the prediction of daytime performance indices, although objective wake time after sleep onset appeared the best single predictor of the daytime measures.

Conclusions:

Results confirm that PI sufferers do show relative psychomotor performance deficits when responding to challenging reaction time tasks, and these deficits appear related to both objective and subjective sleep deficits. Findings support PI patients’ diurnal complaints and suggest the usefulness of complex reaction time tasks for assessing them.

Inter-Individual Differences In Habitual Sleep Timing and Entrained Phase of Endogenous Circadian Rhythms of BMAL1, PER2 and PER3 mRNA in Human Leukocytes

Study Objectives:

Individual sleep timing differs and is governed partly by circadian oscillators, which may be assessed by hormonal markers, or by clock gene expression. Clock gene expression oscillates in peripheral tissues, including leukocytes. The study objective was to determine whether the endogenous phase of these rhythms, assessed in the absence of the sleep-wake and light-dark cycle, correlates with habitual sleep-wake timing.

Design:

Observational, cross-sectional.

Setting:

Home environment and Clinical Research Center.

Participants:

24 healthy subjects aged 25.0 ± 3.5 (SD) years.

Measurements:

Actigraphy and sleep diaries were used to characterize sleep timing. Circadian rhythm phase and amplitude of plasma melatonin, cortisol, and BMAL1, PER2, and PER3 expression were assessed during a constant routine.

Results:

Circadian oscillations were more robust for PER3 than for BMAL1 or PER2. Average peak timings were 6:05 for PER3, 8:06 for PER2, 15:06 for BMAL1, 4:20 for melatonin, and 10:49 for cortisol. Individual sleep-wake timing correlated with the phases of melatonin and cortisol. Individual PER3 rhythms correlated significantly with sleepwake timing and the timing of melatonin and cortisol, but those of PER2 and BMAL1 did not reach significance. The correlation between sleep timing and PER3 expression was stronger in individuals homozygous for the variant of the PER3 polymorphism that is associated with morningness.

Conclusions:

Individual phase differences in PER3 expression during a constant routine correlate with sleep timing during entrainment. PER3 expression in leukocytes represents a useful molecular marker of the circadian processes governing sleep-wake timing.

Meta-Analysis of Short Sleep Duration and Obesity in Children and Adults

Background:

Recent epidemiological studies suggest that short sleep duration may be associated with the development of obesity from childhood to adulthood.

Objectives:

To assess whether the evidence supports the presence of a relationship between short sleep duration and obesity at different ages, and to obtain an estimate of the risk.

Methods:

We performed a systematic search of publications using MEDLINE (1996-2007 wk 40), EMBASE (from 1988), AMED (from 1985), CINHAL (from 1982) and PsycINFO (from 1985) and manual searches without language restrictions. When necessary, authors were contacted. Criteria for inclusion were: report of duration of sleep as exposure, BMI as continuous outcome and prevalence of obesity as categorical outcome, number of participants, age, and gender. Results were pooled using a random effect model. Sensitivity analysis was performed, heterogeneity and publication bias were also checked. Results are expressed as pooled odds ratios (OR [95% confidence intervals, CIs]) and as pooled regression coefficients (β; 95% CIs).

Results:

Of 696 studies identified, 45 met the inclusion criteria (19 in children and 26 in adults) and 30 (12 and 18, respectively) were pooled in the meta-analysis for a total of 36 population samples. They included 634,511 participants (30,002 children and 604,509 adults) from around the world. Age ranged from 2 to 102 years and included boys, girls, men and women. In children the pooled OR for short duration of sleep and obesity was 1.89 (1.46 to 2.43; P < 0.0001). In adults the pooled OR was 1.55 (1.43 to 1.68; P < 0.0001). There was no evidence of publication bias. In adults, the pooled β for short sleep duration was -0.35 (-0.57 to -0.12) unit change in BMI per hour of sleep change.

Conclusions:

Cross-sectional studies from around the world show a consistent increased risk of obesity amongst short sleepers in children and adults. Causal inference is difficult due to lack of control for important confounders and inconsistent evidence of temporal sequence in prospective studies.

Sleep Is Increased By Weight Gain and Decreased By Weight Loss in Mice

Objective:

To determine whether weight loss could reverse excessive sleep in high-fat diet-induced obesity.

Design:

Three groups of mice participated in the study. A weight gain/loss group was fed with high-fat food for 6 weeks (weight gain), and regular food again for 4 weeks (weight loss). A control group and a weight gain only group were fed with regular food and high-fat food, respectively, for 10 weeks after the baseline.

Participants:

Adult male C57BL/6 mice.

Measurements:

The amounts of wake, rapid eye movement sleep (REMS) and non-REM sleep (NREMS) were determined at week 0 (baseline), week 6, and week 10.

Results:

The weight gain/loss group displayed a significant decrease in wakefulness and increases in NREMS and episodes of NREMS during 6 weeks of weight gain, which were reversed during subsequent 4 weeks of weight loss. The weight gain only group displayed significant decrease in wakefulness and increase of NREMS and REMS at both week 6 and week 10. The control group did not show significant sleep alterations during the experiment.

Conclusion:

These observations indicate that sleep alterations induced by weight gain are reversed by weight loss in obese animals. These data may shed light on the mechanisms underlying the well established association between obesity and sleepiness in humans
and may lead to new therapeutic strategies for these 2 increasingly prevalent problems in the modern societies.

Self-Reported Sleep Duration is Associated with the Metabolic Syndrome in Midlife Adults

Study objective:

Short and long sleep duration have been linked to various risk factors for cardiovascular disease. In the present study, we evaluated the relationship between sleep duration and presence of the metabolic syndrome, which is a cluster of physiologically interrelated risk factors for cardiometabolic disease.

Design/Setting:

Cross-sectional community-based cohort study.

Participants:

One thousand two hundred fourteen participants from the Adult Health and Behavior Project registry (aged 30 to 54 years).

Measurements:

Participants were divided into 4 groups based upon their reported sleep duration. The metabolic syndrome was defined according to the American Heart Association/National Heart Lung and Blood Institute’s criteria. Logistic regression was used to test the hypothesis that sleep duration is a significant correlate of the metabolic syndrome and its components.

Results:

The observed metabolic syndrome rate (22%) was similar to that of published health statistics for American adults. After covariate adjustment, the odds for having the metabolic syndrome increased by more than 45% in both short and long sleepers, compared with those sleeping 7 to 8 hours per night. Sleep duration was also associated individually with abdominal obesity, elevated fasting glucose, and hypertriglyceridemia. After further adjustment for use of antihypertensive medication, prevalence of the metabolic syndrome and its components remained elevated in short sleepers only.

Conclusion:

These data suggest that sleep duration is a significant correlate of the metabolic syndrome. Additional studies are needed to evaluate temporal relationships among these measures, the behavioral and physiologic mechanisms that link the two, and their impact on subsequent cardiometabolic disease.

Associations of Usual Sleep Duration with Serum Lipid and Lipoprotein Levels

Study Objectives:

We examined the individual association between sleep duration and a high serum triglyceride, low HDL cholesterol, or high LDL cholesterol level.

Design and Setting:

The present study analyzed data from the National Health and Nutrition Survey that was conducted in November 2003 by the Japanese Ministry of Health, Labour and Welfare. This survey was conducted on residents in the districts selected randomly from all over Japan.

Participants:

The subjects included in the statistical analysis were 1,666 men and 2,329 women aged 20 years or older.

Intervention: N/A

Measurements and Results:

Among women, both short and long sleep durations are associated with a high serum triglyceride level or a low HDL cholesterol level. Compared with women sleeping 6 to 7 h, the relative risk of a high triglyceride level among women sleeping <5 h was 1.51 (95% CI, 0.96-2.35), and among women sleeping ≥8 h was 1.45 (95% CI, 1.00-2.11); the relative risk of a low HDL cholesterol level among women sleeping <5 h was 5.85 (95% CI, 2.29-14.94), and among women sleeping ≥8 h was 4.27 (95% CI, 1.88-9.72). On the other hand, it was observed that the risk of a high LDL cholesterol level was lower among men sleeping ≥8 h. These analyses were adjusted for the following items: age, blood pressure, body mass index, plasma glucose level, smoking habit, alcohol consumption, dietary habits, psychological stress, and taking cholesterol-lowering medications.

Slow Wave Sleep Enhancement with Gaboxadol Reduces Daytime Sleepiness During Sleep Restriction

Study Objectives:

To evaluate the impact of enhanced slow wave sleep (SWS) on behavioral, psychological, and physiological changes resulting from sleep restriction.

Design:

A double-blind, parallel group, placebo-controlled design was used to compare gaboxadol (GBX) 15 mg, a SWS-enhancing drug, to placebo during 4 nights of sleep restriction (5 h/night). Behavioral, psychological, and physiological measures of the impact of sleep restriction were assessed in both groups at baseline, during sleep restriction and following recovery sleep.

Setting:

Sleep research laboratory.

Participants:

Forty-one healthy adults; 9 males and 12 females (mean age: 32.0 ± 9.9 y) in the placebo group and 10 males and 10 females (mean age: 31.9 ± 10.2 y) in the GBX group.

Interventions:

Both experimental groups underwent 4 nights of sleep restriction. Each group received either GBX 15 mg or placebo on all sleep restriction nights, and both groups received placebo on baseline and recovery nights.

Measurements and Results:

Polysomnography documented a SWS enhancing effect of GBX with no group difference in total sleep time during sleep restriction. The placebo group displayed the predicted deficits due to sleep restriction on the multiple sleep latency test (MSLT) and on introspective measures of sleepiness and fatigue. Compared to placebo, the GBX group showed significantly less physiological sleepiness on the MSLT and lower levels of introspective sleepiness and fatigue during sleep restriction. There were no differences between groups on the psychomotor vigilance task (PVT) and a cognitive test battery, but these measures were minimally affected by sleep restriction in this study. The correlation between change from baseline in MSLT on Day 6 and change from baseline in SWS on Night 6 was significant in the GBX group and in both groups combined.

Conclusions:

The results of this study are consistent with the hypothesis that enhanced SWS, in this study produced by GBX, reduces physiological sleep tendency and introspective sleepiness and fatigue which typically result from sleep restriction.

The Developmental Decrease in REM Sleep: The Role of Transmitters and Electrical Coupling

Study Objectives:

This mini-review considers certain factors related to the developmental decrease in rapid eye movement (REM) sleep, which occurs in favor of additional waking time, and its relationship to developmental factors that may influence its potential role in brain development.

Design:

Specifically, we discuss some of the theories proposed for the occurrence of REM sleep and agree with the classic notion that REM sleep is, at the least, a mechanism that may play a role in the maturation of thalamocortical pathways. The developmental decrease in REM sleep occurs gradually from birth until close to puberty in the human, and in other mammals it is brief and coincides with eye and ear opening and the beginning of massive exogenous activation. Therefore, the purported role for REM sleep may change to involve a number of other functions with age.

Measurements and Results:

We describe recent findings showing that morphologic and physiologic properties as well as cholinergic, gamma amino-butyric acid, kainic acid, n-methyl-d-aspartic acid, noradrenergic, and serotonergic synaptic inputs to mesopontine cholinergic neurons, as well as the degree of electrical coupling between mostly noncholinergic mesopontine neurons and levels of the neuronal gap-junction protein connexin 36, change dramatically during this critical period in development. A novel mechanism for sleep-wake control based on well-known transmitter interactions, as well as electrical coupling, is described.

Conclusion:

We hypothesize that a dysregulation of this process could result in life-long disturbances in arousal and REM sleep drive, leading to hypervigilance or hypovigilance such as that observed in a number of disorders that have a mostly postpubertal age of onset.

The Microstructure of Active and Quiet Sleep as Cortical Delta Activity Emerges in Infant Rats

Study objectives:

Previous investigators have suggested that quiet sleep (QS) in rats develops rapidly upon the emergence of cortical delta activity around postnatal day (P)11 and that the presence of half activated” active sleep (AS) suggests that infant sleep is initially disorganized. To address these issues, we examined the temporal organization of sleep states during the second postnatal week in rats as delta activity emerges.

Design:

Subjects were P9, P11, and P13 Sprague-Dawley rats. Electroencephalogram and nuchal electromyogram electrodes were implanted, and data were recorded at thermoneutrality for 2 hours.

Results:

At all ages, using electromyogram and behavioral criteria, QS (defined as nuchal atonia and behavioral quiescence) dominated the first third of each sleep period, whereas AS (defined as nuchal atonia accompanied by myoclonic twitching) dominated the last third. When delta activity, which was first detected at P11, could be added to the definition of QS, gross assessments of sleep-state organization were not altered, although it was now possible to identify brief periods of QS interposed between periods of AS. No evidence of “half-activated” AS was found. Finally, “slow activity transients” were detected and were primarily associated with QS; their rate of occurrence declined as delta activity emerged.

Conclusions:

When delta activity emerges at P11, it integrates smoothly with periods of QS, as defined using electromyogram and behavioral criteria alone. Delta activity helps to refine estimates of QS duration but does not reflect a significant alteration of sleep-state organization. Rather, this organization is expressed much earlier in ontogeny as fluctuations in muscle tone and associated phasic motor activity.

Carotid Blood Flow During REM Sleep

Objective:

The present study was aimed at directly appraising, in the rabbit, the decrease in common carotid blood flow, the occurrence of which during REM sleep was indirectly suggested by previous studies of preoptic-hypothalamic temperature changes during sleep.

Methods:

In 5 unrestrained male rabbits, polygraphic recordings of electroencephalography, electromyography, ear pinna temperature (°C), common carotid mean and peak blood flow (mL/min), and heart rate (beats/min) were carried out across ultradian wake-sleep cycles. In each cycle, epochs of 60 seconds were selected for analysis at the end of nonrapid eye movement (NREM) sleep, at the beginning and end of rapid eye movement (REM) sleep, and at the beginning of the subsequent period of wakefulness. The time basis of measurements within each epoch was a 5-second period (5×12 = 60 seconds). The mean values of the cardiovascular variables in such epochs of 5 animals underwent nonparametric statistical analysis of their changes across epochs.

Conclusion:

A conspicuous decrease in common carotid blood flow is a constant feature of REM sleep in rabbits during several months of recording. This decrease is the result of a marked depression of both peak flow and heart rate. In spite of the unstable systemic hemodynamic conditions revealed by this study, several independent functional and morphologic factors concur to increase the vertebral blood supply to the brain during REM sleep. This increase raises preoptic-hypothalamic temperature, since vertebral artery blood is warmer than carotid artery blood.

Cold Exposure and Sleep in the Rat: REM Sleep Homeostasis and Body Size

Study Objectives:

Exposure to low ambient temperature (Ta) depresses REM sleep (REMS) occurrence. In this study, both short and long term homeostatic aspects of REMS regulation were analyzed during cold exposure and during subsequent recovery at Ta 24°C.

Design:

EEG activity, hypothalamic temperature, and motor activity were studied during a 24-h exposure to Tas ranging from 10°C to —10°C and for 4 days during recovery.

Setting:

Laboratory of Physiological Regulation during the Wake-Sleep Cycle, Department of Human and General Physiology, Alma Mater Studiorum-University of Bologna.

Subjects:

24 male albino rats.

Interventions:

Animals were implanted with electrodes for EEG recording and a thermistor to measure hypothalamic temperature.

Measurements and Results:

REMS occurrence decreased proportionally with cold exposure, but a fast compensatory REMS rebound occurred during the first day of recovery when the previous loss went beyond a “fast rebound” threshold corresponding to 22% of the daily REMS need. A slow REMS rebound apparently allowed the animals to fully restore the previous REMS loss during the following 3 days of recovery.

Conclusion:

Comparing the present data on rats with data from earlier studies on cats and humans, it appears that small mammals have less tolerance for REMS loss than large ones. In small mammals, this low tolerance may be responsible on a short-term basis for the shorter wake-sleep cycle, and on long-term basis, for the higher percentage of REMS that is quickly recovered following REMS deprivation.

¹²³I-MIBG Cardiac Scintigraphy Provides Clues to the Underlying Neurodegenerative Disorder in Idiopathic REM Sleep Behavior Disorder

Objective:

RBD is considered to be a manifestation of an evolving synucleinopathy, such as Parkinson disease (PD), dementia of Lewy bodies (DLB), and multiple system atrophy (MSA). We tested whether the degree of accumulation of cardiac ¹²³I-MIBG scintigraphy can distinguish the clinical syndromes associated with Lewy body-related disease from the syndrome of PSP (a tauopathy) and MSA.

Design:

Cross-sectional.

Setting:

University-based sleep disorders laboratory.

Patients:

Subjects comprised 95 patients (31, idiopathic RBD; 26, PD; 10, MSA; 6, DLB; 13, progressive supranuclear palsy [PSP]) and 9 control subjects.

Intervention:

To compare tracer uptake of cardiac ¹²³I-MIBG between idiopathic RBD, PD, MSA, DLB, and PSP and control subjects.

Measurements and Results:

Cardiac ¹²³I-MIBG accumulation was evaluated by the heart/mediastinum (H/M) ratio. Mean value of the H/M ratio (early, delayed) was significantly reduced in patients with idiopathic RBD compared to MSA patients, PSP patients, control subjects (P < 0.001 in each group) and PD patients in early images (P < 0.05). There was a correlation between the H/M ratio and disease duration in the idiopathic RBD group. ROC analysis revealed that an H/M cut-off value of 1.9 was useful for differentiating RBD from MSA and PSP as well as distinguishing control subjects from those with RBD in both early and delayed images.

Conclusion:

Cardiac ¹²³I-MIBG findings are similar among idiopathic RBD and the syndromes of PD and DLB, but differ from those of PSP and MSA.

Quantification of Electromyographic Activity During REM Sleep in Multiple Muscles in REM Sleep Behavior Disorder

Study Objectives:

The aim of our study was to determine which muscle or combination of muscles (either axial or limb muscles, lower or upper limb muscles, or proximal or distal limb muscles) provides the highest rates of rapid eye movement (REM) sleep phasic electromyographic (EMG) activity seen in patients with REM sleep behavior disorder (RBD).

Setting:

Two university hospital sleep disorders centers.

Participants:

Seventeen patients with idiopathic RBD (n = 8) and RBD secondary to Parkinson disease (n = 9).

Interventions: Not applicable.

Measurements and Results:

Patients underwent polysomnography, including EMG recording of 13 different muscles. Phasic EMG activity in REM sleep was quantified for each muscle separately. A mean of 1459.6 ± 613.8 three-second REM sleep mini-epochs were scored per patient. Mean percentages f phasic EMG activity were mentalis (42 ± 19), flexor digitorum superficialis (29 ± 13), extensor digitorum brevis (23 ± 12), abductor pollicis brevis (22 ± 11), sternocleidomastoid (22 ± 12), deltoid (19 ± 11), biceps brachii (19 ± 11), gastrocnemius (18 ± 9), tibialis anterior (right, 17 ± 12; left, 16 ± 10), rectus femoris (left, 11 ± 6; right, 9 ± 6), and thoraco-lumbar paraspinal muscles (6 ± 5). The mentalis muscle provided significantly higher rates of excessive phasic EMG activity than all other muscles but only detected 55% of all the mini-epochs with phasic EMG activity. Simultaneous recording of the mentalis, flexor digitorum superficialis, and extensor digitorum brevis muscles detected 82% of all mini-epochs containing phasic EMG activity. This combination provided higher rates of EMG activity than any other 3-muscle combination. Excessive phasic EMG activity was more frequent in distal than in proximal muscles, both in upper and lower limbs.

Conclusion:

Simultaneous recording of the mentalis, flexor digitorum superficialis, and extensor digitorum brevis muscles provided the highest rates of REM sleep phasic EMG activity in subjects with RBD.

Association between Nighttime Sleep and Napping in Older Adults

Study Objectives:

Napping might indicate deficiencies in nighttime sleep, but the relationship is not well defined. We assessed the association of nighttime sleep duration and fragmentation with subsequent daytime sleep.

Design:

Cross-sectional study.

Participants:

235 individuals (47.5% men, 29.7% black), age 80.1 (2.9) years.

Measurements and Results:

Nighttime and daytime sleep were measured with wrist actigraphy and sleep diaries for an average of 6.8 (SD 0.7) nights. Sleep parameters included total nighttime sleep (h), movement and fragmentation index (fragmentation), and total daytime sleep (h). The relationship of total nighttime sleep and fragmentation to napping (yes/no) was assessed using logistic regression. In individuals who napped, mixed random effects models were used to determine the association between the previous night sleep duration and fragmentation and nap duration, and nap duration and subsequent night sleep duration. All models were adjusted for age, race, gender, BMI, cognitive status, depression, cardiovascular disease, respiratory symptoms, diabetes, pain, fatigue, and sleep medication use. Naps were recorded in sleep diaries by 178 (75.7%) participants. The odds ratios (95% CI) for napping were higher for individuals with higher levels of nighttime fragmentation (2.1 [0.8, 5.7]), respiratory symptoms (2.4 [1.1, 5.4]), diabetes (6.1 [1.2, 30.7]), and pain (2.2 [1.0, 4.7]). Among nappers, neither sleep duration nor fragmentation the preceding night was associated with nap duration the next day.

Conclusion:

More sleep fragmentation was associated with higher odds of napping although not with nap duration. Further research is needed to determine the causal association between sleep fragmentation
and daytime napping.

Factors Associated with Concordance and Variability of Sleep Quality in Persons with Alzheimer’s Disease and their Caregivers

Study Objectives:

To describe the day-to-day variation in sleep characteristics and the concordance between nighttime sleep of persons with Alzheimer’s disease (AD) and their family caregivers.

Participants:

N = 44 community-dwelling older adults with probable or possible AD and their co-residing family caregivers.

Design:

Participants wore an Actillume (Ambulatory Monitoring, Inc) for one week and completed an assessment battery to evaluate patient and caregiver mood, physical function, medication use, caregiver behavior management style, and patient cognitive status.

Measurements and Results:

Actigraphically derived sleep measures included bedtime, rising time, total time in bed, total sleep time, number of awakenings, total wake time, and sleep percent (efficiency). For each sleep parameter, total variance was determined for between-subject variance and within-subject variance from day-to-day. Sleep concordance was examined using multinomial logistic regression to compare trichotomous patient-caregiver combinations of good and bad sleepers. For both patients and caregivers, between-subject daily variability accounted for more of the variance in sleep than within-subject variability. Patient depression and caregiver management style were significant predictors both for concordant poor sleep (both patient and caregiver with sleep efficiency <85%) and patient-caregiver sleep discordance.

Conclusions:

This study provides data that sleep disturbances for persons with AD and their family caregivers vary considerably night to night, and that poor sleep in one member of the caregiving dyad is not necessarily linked to disturbed sleep in the other. Understanding the complex interrelationship of sleep in AD patients and caregivers is an important first step towards the development of individualized and effective treatment strategies.

MX2 Gene Expression Tends to be Downregulated in Subjects with
HLA-DQB1*0602

Objective:

There is a close association between narcolepsy and the human leukocyte antigen (HLA)-DQB1*0602. The detailed influence and function of this specific HLA allele with regard to narcolepsy have not yet been elucidated. Our previous report identified the myxovirus resistance 2 (MX2) gene as a narcolepsy-specific dysregulated gene; however, the report had a limitation–the control groups were not HLA matched. In this study, we examined the possibility of an association between MX2 expression and HLA haplotypes.

Designs:

The expression levels of the MX2 gene in 3 groups (24 narcolepsy with cataplexy patients; 24 age-, sex-, and HLA-DQB1 genotypematched controls; and 24 age- and sex-matched controls without the HLA-DQB1*0602 allele) were measured by quantitative real-time RTPCR.

Results:

The expression level of the MX2 gene tended to be downregulated in subjects carrying HLA-DQB1*0602, compared with that of the control subjects without this allele. There was no difference in the MX2 expression level between the narcolepsy subjects and the HLA-DQB1 genotype-matched control subjects.

Conclusion:

Our previous finding–the narcolepsy-specific reduction of MX2 gene expression–was not replicated in this follow-up study. The expression level of the MX2 gene in white blood cells was found to be lower in subjects with the HLA-DQB1*0602 than in subjects without this allele, suggesting that there exists a relationship between the HLADQB1* 0602 allele and MX2 gene expression. This might be a possible explanation for the strong HLA association observed in narcolepsy.

BOOK REVIEW - Sleep and Pain
Edited by Giles Lavigne, Barry J. Sessle, Manon Choiniere, and Peter J. Soja
International Association for the Study of Pain (IASP) Press, (Seattle); ISBN 0-031092-62-0

BOOK REVIEW - Sleep and Pain

Thank You SLEEP Reviewers for 2007