Shahrad Taheri

Short Sleep Duration Is Associated with Reduced Leptin, Elevated Ghrelin, and Increased Body Mass Index

Background Sleep duration may be an important regulator of body weight and metabolism. An association between short habitual sleep time and increased body mass index (BMI) has been reported in large population samples. The potential role of metabolic hormones in this association is unknown. Methods and Findings Study participants were 1,024 volunteers from the Wisconsin Sleep Cohort Study, a population-based longitudinal study of sleep disorders. Participants underwent nocturnal polysomnography and reported on their sleep habits through questionnaires and sleep diaries. Following polysomnography, morning, fasted blood samples were evaluated for serum leptin and ghrelin (two key opposing hormones in appetite regulation), adiponectin, insulin, glucose, and lipid profile. Relationships among these measures, BMI, and sleep duration (habitual and immediately prior to blood sampling) were examined using multiple variable regressions with control for confounding factors. A U-shaped curvilinear association between sleep duration and BMI was observed. In persons sleeping less than 8 h (74.4% of the sample), increased BMI was proportional to decreased sleep. Short sleep was associated with low leptin (p for slope = 0.01), with a predicted 15.5% lower leptin for habitual sleep of 5 h versus 8 h, and high ghrelin (p for slope = 0.008), with a predicted 14.9% higher ghrelin for nocturnal (polysomnographic) sleep of 5 h versus 8 h, independent of BMI. Conclusion Participants with short sleep had reduced leptin and elevated ghrelin. These differences in leptin and ghrelin are likely to increase appetite, possibly explaining the increased BMI observed with short sleep duration. In Western societies, where chronic sleep restriction is common and food is widely available, changes in appetite regulatory hormones with sleep curtailment may contribute to obesity.

The link between short sleep duration and obesity: we should recommend more sleep to prevent obesity

Sleep may affect energy balance. Sleep may not be the only answer to the obesity pandemic, but its effect should be considered seriously, as even small changes in the energy balance are beneficial. Good sleep could be part of the obesity prevention approach.

Sleeping with the hypothalamus: emerging therapeutic targets for sleep disorders.

Delineating the basic mechanisms that regulate sleep will likely result in the development of better treatments for sleep disorders. The hypothalamus is now recognized as a key center for sleep regulation, with hypothalamic neurotransmitter systems providing the framework for therapeutic advances. An increased awareness of the close interaction between sleep and homeostatic systems is also emerging. Progress has occurred in the understanding of narcolepsy—molecular techniques have identified the lateral hypothalamic hypocretin (orexin) neuropeptide system as key to the disorder. Other sleep disorders are now being tackled in the same way and are likely to yield to efforts combining basic and clinical research. Here we highlight the role of the hypothalamus in sleep physiology and discuss neurotransmitter systems, such as adenosine, dopamine, GABA, histamine and hypocretin, that may have therapeutic applications for sleep disorders.

Diurnal variation in orexin A immunoreactivity and prepro-orexin mRNA in the rat central nervous system

Orexins are a family of neuropeptides originally believed to be important mediators of food intake. The wide distribution of orexins and their receptors, however, has suggested other regulatory functions for these peptides including involvement in sleep and arousal mechanisms. In this study, we have demonstrated diurnal variation in orexin A immunoreactivity in the pons, from where locus coeruleus noradrenergic neurones innervate other brain areas to stimulate arousal, and in the preoptic/anterior hypothalamic region, an area implicated in the regulation of sleep and circadian rhythms. Orexin A immunoreactivity decreased by 50% in the preoptic/anterior hypothalamus from 09:00 to 21:00 h (P < 0.0001), whilst in the pons, it increased by over 30% from 09:00 to 01:00 h (P = 0.02). Prepro-orexin mRNA also displayed diurnal variation. This further suggests that orexins are involved in the regulation of the sleep/wake cycle.

Distribution and quantification of immunoreactive orexin A in rat tissues

A sensitive and specific radioimmunoassay for orexin A was developed. Orexin A immunoreactivity was found to be confined to the central nervous system (CNS) with the highest concentrations in the hypothalamus, inferior and superior colliculi and brainstem. Within the hypothalamus, the highest levels were found in the lateral and posterior hypothalamus. These regions had a greater orexin A content in females compared to males. The orexin A content of hypothalamic regions did not change with fasting and no difference was noted in hypothalami of rats fed a high fat diet. The hypothalamic orexin A content was not different in obese Zucker rats compared to lean controls. Thus, orexin A has a wide distribution in the CNS, but appetite regulation may not be its main function.

The genetics of sleep disorders

The contribution of genetic components to the pathology of sleep disorders is increasingly recognised as important. Genetic studies have identified genes that may be important in the regulation of circadian rhythms, which in turn determine the time of sleep onset and waking. Recent studies have shown that mutations in hPER2 are associated with autosomal-dominant familial advanced-sleep-phase syndrome. Genetic studies in a canine model of narcolepsy and in knock-out mice have led to the identification of the hypothalamic hypocretin (orexin) neurotransmitter system as a key target for human narcolepsy. The contribution of genetic factors to obstructive sleep apnoea syndrome (OSAS) has led to a better understanding of this complex disorder that may be part of a larger syndrome associated with respiratory, cardiovascular, and metabolic dysfunction. The aim of this review is to discuss the current knowledge on the role of genetic factors in sleep disorders, in particular circadian disorders, narcolepsy, restless-legs syndrome, and OSAS.

Childhood sleep duration and associated demographic characteristics in an English cohort

STUDY OBJECTIVES To provide reference data on sleep duration throughout childhood and explore the demographic characteristics associated with sleep. DESIGN Population-based prospective longitudinal birth-cohort study. SETTING South-West England, children born in 1991-1992 and followed since birth. PARTICIPANTS Eleven thousand five hundred children with repeat measures of sleep from birth based on parent-reported questionnaires. Data on daytime and nighttime sleep duration and timings and night awakenings at 8 timepoints from age 6 months to 11 years. RESULTS Total sleep duration steadily fell from 13 hours and 12 minutes during infancy to 9 hours and 49 minutes at 11 years of age. Compared with earlier studies, the younger children in this cohort slept for a shorter period. The variation in sleep duration was very wide: from 10 to 17 hours in early infancy, narrowing to 8.5 to 11 hours at 11 years. Half of the children at preschool age woke at least once during the night, but frequent waking (> 3 times) peaked in infancy (10% of all infants) and steadily declined in the preschool-aged years. Despite going to bed at the same time, girls slept consistently longer than boys (by 5-10 minutes). Children from low-income families went to bed later and woke up later, but there was little difference in total sleep duration. Children of younger mothers (< 21 years) slept longer, whereas children of older mothers (> 35 years) slept persistently less. Children in larger families tended to go to bed later, as did the minority group of non-White children in the cohort. CONCLUSIONS Given the wide natural variation of sleep in the childhood population, any recommendations on optimal sleep duration at any age must take into account considerable individual variability.

Effectiveness of lifestyle interventions on obstructive sleep apnea (OSA): systematic review and meta-analysis.

BACKGROUND Obstructive sleep apnea (OSA) is a common sleep disorder associated with several adverse health outcomes. Given the close association between OSA and obesity, lifestyle and dietary interventions are commonly recommended to patients, but the evidence for their impact on OSA has not been systematically examined. OBJECTIVES To conduct a systematic review and meta-analysis to assess the impact of weight loss through diet and physical activity on measures of OSA: apnea-hypopnea index (AHI) and oxygen desaturation index of 4% (ODI4). METHODS A systematic search was performed to identify publications using Medline (1948-2011 week 40), EMBASE (from 1988-2011 week 40), and CINAHL (from 1982-2011 week 40). The inverse variance method was used to weight studies and the random effects model was used to analyze data. RESULTS Seven randomized controlled trials (519 participants) showed that weight reduction programs were associated with a decrease in AHI (-6.04 events/h [95% confidence interval -11.18, -0.90]) with substantial heterogeneity between studies (I(2) = 86%). Nine uncontrolled before-after studies (250 participants) showed a significant decrease in AHI (-12.26 events/h [95% confidence interval -18.51, -6.02]). Four uncontrolled before-after studies (97 participants) with ODI4 as outcome also showed a significant decrease in ODI4 (-18.91 episodes/h [95% confidence interval -23.40, -14.43]). CONCLUSIONS Published evidence suggests that weight loss through lifestyle and dietary interventions results in improvements in obstructive sleep apnea parameters, but is insufficient to normalize them. The changes in obstructive sleep apnea parameters could, however, be clinically relevant in some patients by reducing obstructive sleep apnea severity. These promising preliminary results need confirmation through larger randomized studies including more intensive weight loss approaches.

Associations between specific technologies and adolescent sleep quantity, sleep quality, and parasomnias

OBJECTIVE We tested the hypothesis that weekday bedtime use of six technologies would be significantly associated with eight sleep parameters studied relating to sleep quantity, sleep quality, and parasomnias. METHODS In our cross-sectional study, we previously administered validated age-appropriate questionnaires (School Sleep Habits Survey, Technology Use Questionnaire). Participating adolescents (n=738; 54.5% boys) were aged 11-13 years and were from the Midlands region of the United Kingdom in 2010. RESULTS Frequent use of all technology types was significantly inversely associated with weekday sleep duration (hours). Frequent music listeners and video gamers had significantly prolonged sleep onset (β=7.03 [standard error {SE}, 2.66]; P<.01 and β=6.17 [SE, 2.42]; P<.05, respectively). Frequent early awakening was significantly associated with frequent use of all technology types. The greatest effect was observed in frequent television viewers (odds ratio [OR], 4.05 [95% confidence interval {CI}, 2.06-7.98]). Difficulty falling asleep was significantly associated with frequent mobile telephone use, video gaming, and social networking, with music listeners demonstrating the greatest effect (OR, 2.85 [95%CI, 1.58-5.13]). Music listeners were at increased risk for frequent nightmares (OR, 2.02 [95% CI, 1.22-3.45]). Frequent use of all technologies except for music and mobile telephones was significantly associated with greater cognitive difficulty in shutting off. Frequent television viewers were almost four times more likely to report higher sleepwalking frequency (OR, 3.70 [95% CI, 1.89-7.27]). CONCLUSIONS Frequent weekday technology use at bedtime was associated with significant adverse effects on multiple sleep parameters. If confirmed in other samples and longitudinally, improving sleep hygiene through better management of technology could enhance the health and well-being of adolescent populations.

CSF hypocretin levels in Guillain–Barré syndrome and other inflammatory neuropathies

CSF hypocretin-1 was measured in 28 Guillain–Barré syndrome (GBS), 12 Miller–Fisher syndrome, 12 chronic inflammatory demyelinating polyneuropathy (CIDP), and 48 control subjects. Seven GBS subjects had undetectably low hypocretin-1 levels (<100 pg/mL). Hypocretin-1 levels were moderately reduced in an additional 11 GBS, 5 Miller–Fisher syndrome, and 1 CIDP subject. Low levels in GBS occurred early in the disease and were associated with upper CNS level abnormalities.