Category: Sleep Disorders

Researchers at the Allen Institute for Brain Science and SRI International have published the most systematic study to date of the effects of sleep deprivation on gene expression in the brain. The findings have implications for improving the understanding and management of the adverse effects of sleep deprivation on brain function.

The study, available in Frontiers in Neuroscience, has created an extensive and detailed map of gene activity, known as gene expression, in the mouse brain across five behavioral conditions including sleeping, waking and sleep deprivation. Activity of approximately 220 genes responding to these conditions was examined in detail, down to the cellular level, throughout the brain. Additionally, seven brain areas were examined by DNA microarray analysis, which reports the expression levels of tens of thousands of genes and allows a genome-wide analysis of the consequences of sleep deprivation.

"Although most people experience occasional sleep deprivation and recognize its impact on their mood and behavior, there is little scientific understanding of how sleep loss actually affects brain function," said Thomas Kilduff, Ph.D., senior director of the Center for Neuroscience at SRI International. "This pioneering study documents how extending wakefulness affects gene expression in specific brain regions and describes a 'molecular anatomical signature' of sleep deprivation. Our findings may contribute to treatments that will help improve sleep quality and reduce problems arising from sleep deprivation."

By comparing which genes were turned on and where in the brain across the different conditions, the researchers discovered that the majority of the neurons in the forebrain were affected in diverse ways by sleep deprivation, painting a dynamic picture of the molecular consequences of sleep deprivation on higher cognitive functions. Affected forebrain regions include the neocortex, amygdala and hippocampus, which mediate cognitive, emotional and memory functions that are impaired by sleep deprivation.

Detailed analysis of 209 brain areas revealed a novel set of genes not previously associated with sleep deprivation, including genes associated with the stress response, cell-cell signaling, and the regulation of other genes. One gene, neurotensin, has been implicated in schizophrenia and is similarly induced by antipsychotic drugs. These genes may provide potential targets for therapeutic intervention to alleviate the effects of sleep deprivation.

"These data illustrate the complex and dynamic relationship between sleep and sleep deprivation, neuroanatomical pathways and gene expression," said Ed Lein, Ph.D., senior director of neuroscience at the Allen Institute for Brain Science and senior author of the study. "The breadth and level of detail provided by these data will be a unique resource for the scientific community, and to that end we have made the data set publicly available online in its entirety."

The resulting open data resource is one of a growing collection of public online resources provided by the Allen Institute, which was founded by philanthropist Paul G. Allen to advance brain research.

Sleep deprivation leads to a range of cognitive, attention and emotional deficits, including irritability and impaired memory, coordination, and concentration. These effects, which can compromise health, performance and safety, are common among those who work extended hours, including military and medical personnel, and others suffering from chronic sleep loss. Sleep deficits have also been linked to the development of some chronic diseases and disorders, including diabetes, depression, obesity and cardiovascular disease.

The control of sleeping and waking and the consequences of sleep deprivation are believed to be associated with gene activity changes in brain regions involved in sleep regulation and higher level functions. Understanding these changes in gene activity is a critical step toward advances in the treatment of sleep disorders and mitigation of the effects of sleep deprivation.

The data in this study are publicly available via the ALLEN Brain Atlas data portal (www.brain-map.org) as the "Sleep Study." This online dataset comprises a substantial collection of data detailing where specific genes are expressed, or "turned on," throughout the mouse brain for five conditions of sleeping and waking. Specifically, it includes searchable image-based gene expression data for approximately 220 sleep-related genes, genome-wide microarray data for seven sleep-associated brain areas, and a 3D viewing tool for visualizing changes in gene expression across different conditions.

This public resource is a unique resource for sleep researchers worldwide and holds promise for accelerating progress toward understanding and effective treatment of sleep disorders.

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Journal Reference:

1. C.L. Thompson et al. Molecular and anatomical signatures of sleep deprivation in the mouse brain. Frontiers in Neuroscience, 2010; DOI: 10.3389/fnins.2010.00165

It is one thing to learn a new piece of information, such as a new phone number or a new word, but quite another to get your brain to file it away so it is available when you need it.

A new study published in the Journal of Neuroscience by researchers at the University of York and Harvard Medical School suggests that sleep may help to do both.

The scientists found that sleep helps people to remember a newly learned word and incorporate new vocabulary into their "mental lexicon."

During the study, which was funded by the Economic and Social Research Council, researchers taught volunteers new words in the evening, followed by an immediate test. The volunteers slept overnight in the laboratory while their brain activity was recorded using an electroencephalogram, or EEG. A test the following morning revealed that they could remember more words than they did immediately after learning them, and they could recognise them faster demonstrating that sleep had strengthened the new memories.

This did not occur in a control group of volunteers who were trained in the morning and re-tested in the evening, with no sleep in between. An examination of the sleep volunteers' brainwaves showed that deep sleep (slow-wave sleep) rather than rapid eye movement (REM) sleep or light sleep helped in strengthening the new memories.

When the researchers examined whether the new words had been integrated with existing knowledge in the mental lexicon, they discovered the involvement of a different type of activity in the sleeping brain. Sleep spindles are brief but intense bursts of brain activity that reflect information transfer between different memory stores in the brain — the hippocampus deep in the brain and the neocortex, the surface of the brain.

Memories in the hippocampus are stored separately from other memories, while memories in the neocortex are connected to other knowledge. Volunteers who experienced more sleep spindles overnight were more successful in connecting the new words to the rest of the words in their mental lexicon, suggesting that the new words were communicated from the hippocampus to the neocortex during sleep.

Co-author of the paper, Professor Gareth Gaskell, of the University of York's Department of Psychology, said: "We suspected from previous work that sleep had a role to play in the reorganisation of new memories, but this is the first time we've really been able to observe it in action, and understand the importance of spindle activity in the process."

These results highlight the importance of sleep and the underlying brain processes for expanding vocabulary. But the same principles are likely to apply to other types of learning.

Lead author, Dr Jakke Tamminen, said: "New memories are only really useful if you can connect them to information you already know. Imagine a game of chess, and being told that the rule governing the movement of a specific piece has just changed. That new information is only useful to you once you can modify your game strategy, the knowledge of how the other pieces move, and how to respond to your opponent's moves. Our study identifies the brain activity during sleep that organises new memories and makes those vital connections with existing knowledge."

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Journal Reference:

1. J. Tamminen, J. D. Payne, R. Stickgold, E. J. Wamsley, M. G. Gaskell. Sleep Spindle Activity is Associated with the Integration of New Memories and Existing Knowledge. Journal of Neuroscience, 2010; 30 (43): 14356 DOI: 10.1523/JNEUROSCI.3028-10.2010

A study in the Nov. 1 issue of the journal Sleep found that vulnerability to sleep deprivation is influenced by the interaction between waking social activity and individual personality traits.

Results show that extroverts who were exposed to 12 hours of social interaction were more vulnerable to subsequent sleep deprivation than those who were exposed to an identical period of isolated activity. Speed on the Psychomotor Vigilance Task (PVT) for extroverts in the socially enriched group was significantly slower at 4 a.m., 6 a.m. and noon compared with speed for extroverts in the socially impoverished condition. Introverts' speed on the PVT was relatively unaffected by prior social exposure.

"Extroverts exposed to socially enriched environments showed greater vulnerability to subsequent sleep deprivation than did extroverts exposed to an identical but socially impoverished environment," said principal investigator and lead author Tracy L. Rupp, PhD, research psychologist in the Behavioral Biology Branch of the Center for Military Psychiatry and Neuroscience at Walter Reed Army Institute of Research in Silver Spring, Md. "The ability of introverts to resist sleep loss was relatively unaffected by the social environment. Overall, the present results might also be interpreted more generally to suggest that waking experiences, along with their interaction with individual characteristics, influence vulnerability to subsequent sleep loss."

The study involved 48 healthy adults between 18 and 39 years of age. Participants were prescreened using the NEO Personality Inventory Revised, and on the day of arrival for the study they were classified as extroverted (n=23) or introverted (n=25) using the Eysenck Personality Questionnaire-Revised.

After a night of baseline sleep that was measured by polysomnography, participants remained awake for a total of 36 hours, which included a 12-hour social-exposure condition followed by 22 hours of sleep deprivation. Twenty-four participants were randomly assigned to the "socially enriched group," participating in controlled and structured group activities from 10 a.m. to 10 p.m. and interacting socially with four research technicians. Activities included interactive card and board games, puzzles, group discussions and movies. The 24 participants who were assigned to the "socially impoverished group" completed similar activities in relative isolation in their private rooms. Objective alertness was measured by hourly testing, alternating the PVT with the Maintenance of Wakefulness Test (MWT).

Results show that there were no significant differences in measured sleep parameters between extroverts and introverts on the baseline night. Although differences in PVT performance were not evident during the social-exposure condition, introverts were more alert than extroverts on the MWT.

According to the authors, social interactions are cognitively complex experiences that may lead to rapid fatigue in brain regions that regulate attention and alertness. Therefore, high levels of social stimulation may be associated with an increase in the need for sleep. However, some individuals have a trait-like resistance to sleep loss that appears to be rooted in genetic differences. In particular, introverts may have higher levels of cortical arousal, giving them greater resistance to sleep deprivation.

Rupp noted that the results may have implications for industries that require workers to maintain alertness during periods of sustained wakefulness. Potential performance consequences resulting from team assignments or independent work may vary depending on an individual's personality traits.

"These data have practical relevance for occupational shift work and military operational assignments, and theoretical implications for understanding individual-difference factors influencing vulnerability or resiliency to sleep loss."

The study was supported by the U.S. Army Medical Research and Materiel Command.

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Journal Reference:

1. Tracy L. Rupp, William D.S. Killgore, Thomas J. Balkin. Socializing by day may affect performance by night: vulnerability to sleep deprivation is differentially mediated by social exposure in extraverts vs introverts. Sleep, 2010; 33 (11): 1475-1485 [link]

Experts at the University of Surrey discovered that many older people felt that they may be branded lazy for taking afternoon naps so they tried hard to avoid nodding off.

But the occasional nap can make older people more able to lead a fully active life by giving them enough energy to take part in recreational and social activities.

Susan Venn, of the Department of Sociology said: "Sleep is central to health and well-being, but as people get older, the quality of their sleep can deteriorate. They shouldn't feel guilty or think themselves lazy for having a nap."

The new research also found that as older people often have more disturbed sleep patterns at night they try to avoid taking a nap during the day only to fall asleep watching television during the early evening. As a result they may end up feeling exhausted..

Another finding was that older men and women lose sleep because of having to get up several times a night to go to the toilet, so they may cut down on drinking fluids during the day believing this will help, even though they may become dehydrated.

One interviewee, called Anne, aged 71, from Berkshire, said "My main sleep problem is waking up in the early hours of the morning and not being able to get back to sleep.

"I sometimes find on a particularly bad night that I'm awake for three or four hours. I don't want to disturb my husband by tossing and turning, and trying to get back to sleep, so I tend to get up and do the housework, watch DVDs or use the computer.

"Sleep at the moment is a disappointment I suppose, because I feel I've improved my life style by doing all the things, diet, exercise and all this, and I'd hoped that the sleep would improve more than it has."

Susan Venn, of the Department of Sociology, a researcher on the project, explained: "Many of the older people we talked to described how disturbed their sleep was, especially in terms of waking up a lot in the night.

"Anne was like many of the older people we spoke to in that being active during the day was very important to them, and if they slept badly, it impacted on how much could be achieved.

"Many older people are prescribed medications to help them sleep, but research has shown that sleeping medication may impact on the lives of older people, such as increasing the risk of falls."

The new research called "Understanding poor sleep in the community" is linked to an academic conference on sleep issues among older people, based on the SomnIA (Sleep in Ageing) project (www.somnia.surrey.ac.uk).

The research by academics at the University of Surrey, along with colleagues at other institutions, tried to find ways of improving the sleep patterns of older people.

Researchers talked to 62 older men and women who are living in their own homes about their poor sleep patterns and three key findings emerged:

• Whilst many older people do not sleep well and feel tired during the day, they often do not want to take a nap because they believe daytime sleeping is a sign of laziness.
• Older people often get up in the night to go to the toilet, sometimes even several times a night. So, counter to current advice to drink plenty of fluids during the day, they may often severely restrict how much they drink.

• Older men and women would rather not visit their doctor for problems with their sleep, largely because of a concern they will be prescribed some form of sleeping medication. Keeping busy and active is important to many older people and they are concerned that sleeping medication may take away that control. Women, more than men, tended to explore alternative treatments and remedies for poor sleep, such as over the counter remedies and herbal medicines.

The research is linked to a conference called 'Sleep, Well-Being and Active Ageing: New Evidence for Policy and Practice' to be held on Thursday 28th October 2010, Church House Conference Centre, Westminster, London.

Ever wonder why some people breeze along on four hours of sleep when others can barely function? It may be in our genes, according to new research and an accompanying editorial published in the October 26, 2010, print issue of Neurology®, the medical journal of the American Academy of Neurology.

The study looked at people who have a gene variant that is closely associated with narcolepsy, a sleep disorder that causes excessive daytime sleepiness. However, having the gene variant, called DQB1*0602, does not mean that a person will develop narcolepsy; depending on the population, 12 to 38 percent of those with the variant do not have the sleep disorder and are considered healthy sleepers. Also, people without the gene variant can develop narcolepsy, though this is less common.

For the study, 92 healthy adults without the gene variant were compared to 37 healthy adults who had the gene variant but did not have any sleep disorders. All of the participants came to a sleep laboratory. For the first two nights, they spent 10 hours in bed and were fully rested. The next five nights they underwent chronic partial sleep deprivation, also known as sleep restriction, where they were allowed four hours in bed per night. During the remaining time, lights were kept on and participants could read, play games, or watch movies to help them stay awake.

Researchers measured their sleep quality and self-rated sleepiness and tested their memory, attention and ability to resist sleep during the daytime.

The people with the DQB1*0602 gene variant were sleepier and more fatigued while both fully rested and sleep deprived. Their sleep was more fragmented. For example, those with the gene variant woke up on average almost four times during the fifth night of sleep deprivation, compared to those without the gene variant, who woke up on average twice. Those with the gene variant also had a lower sleep drive, or desire to sleep, during the fully rested nights.

Those with the gene variant also spent less time in deep sleep than those without the variant, during both the fully rested and sleep deprivation nights. During the second fully rested night, those with the variant had an average of 34 minutes in stage three sleep, compared to 43 minutes for those without the variant. During the fifth night of sleep deprivation, those with the variant spent an average of 29 minutes in stage three sleep, compared to 35 minutes for those without the variant.

The two groups performed the same on the tests of memory and attention. There was also no difference in their ability to resist sleep during the daytime.

"This gene may be a biomarker for predicting how people will respond to sleep deprivation, which has significant health consequences and affects millions of people around the world. It may be particularly important to those who work on the night shift, travel frequently across multiple time zones, or just lose sleep due to their multiple work and family obligations. However, more research and replication of our findings are needed," said lead study author Namni Goel, PhD, of the University of Pennsylvania School of Medicine in Philadelphia.

The study was supported by the National Space Biomedical Research Institute, the National Institutes of Health, the Institute for Translational Medicine and Therapeutics and the National Center for Research Resources.

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Journal References:

1. Namni Goel, Siobhan Banks, Emmanuel Mignot, David F. Dinges. DQB1*0602 predicts interindividual differences in physiologic sleep, sleepiness, and fatigue. Neurology, 2010; 75: 1509-1519 [link]
2. Amit Verma and Aparajitha K. Verma. Why do we respond differently to sleep deprivation?: It's in our genes!. Neurology, 2010; 75: 1492-1493 [link]

Sleep disturbances increase the risk of work disability and may slow the return to work process. This is especially true in cases where work disability is due to mental disorders or musculoskeletal diseases. These results come from a recent study conducted by the Finnish Institute of Occupational Health in collaboration with the universities of Turku and London.

The research is being conducted as part of two major research projects on social capital in the workplace (Kunta10) and on well-being in the hospital workplace. The follow-up study is part of the Academy of Finland Research Programme on The Future of Work and Well-being (WORK) and the Responding to Public Health Challenges Research Programme (SALVE).

Sleep disturbances include difficulties initiating sleep, intermittent and non-restorative sleep, and waking up too early. The occurrence of these disturbances was studied in 56,732 public sector employees in Finland. During the three-year follow-up, 7 per cent of them were incapacitated for work. Data on work disability and sickness absences lasting 90 days or longer, disability pensions and deaths were obtained from national registers. The associations of sleep disturbances with returning to work were studied in employees who were on long-term sickness leave or retired on disability pension.

Just over one-fifth or 22 per cent of the employees studied reported sleep disturbances on at least five nights a week. A further 26 per cent reported sleep disturbances on 2-4 nights a week. In the former group, the risk of work disability for any reason was one and a half times greater than in employees who reported sleep disturbances once a week or less often.

The risk of work disability due to mental health problems or musculoskeletal disorders was elevated both in employees reporting mild and in those with severe sleep disturbances. Severe sleep disturbances were also associated with work disability due to cardiovascular diseases, neurological diseases and external reasons such as accidents.

Sixty per cent of the employees who were incapacitated returned to work within two years. The risk of a delayed return to work was higher among those whose work disability was due to musculoskeletal disorders. Among men whose incapacity was due to mental health diseases, both mild and severe sleep disturbances predicted a slower return to work.

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Journal Reference:

1. Salo P; Oksanen T; Sivertsen B; Hall M; Pentti J; Virtanen M; Vahtera J; Kivimäki M. Sleep disturbances as a predictor of cause-specific work disability and delayed return to work. Sleep, 2010;33(10):1323-1331 [link]

The impact of upper GI conditions, like gastroesophageal reflux disease (GERD) and functional dyspepsia, on sleep — and treatments aimed at providing relief to heartburn/acid reflux patients who suffer from disordered sleep — were explored in three new studies related to sleep dysfunction presented at the American College of Gastroenterology's (ACG) 75th Annual Scientific meeting in San Antonio, Texas.

Functional dyspepsia is a common, but poorly understood, upper GI condition affecting approximately 10 percent of U.S. adults. The condition is described as chronic abdominal pain and a sensation of fullness, pressure or discomfort in the upper abdomen. This sensation is associated with eating as symptoms usually worsen after meals.

While the prevalence of disordered sleep in patients with functional dyspepsia is unknown, a new study found that disordered sleep is significantly more common in functional dyspepsia patients than in healthy controls.

Patients with functional dyspepsia were 3.25 times more likely to have disordered sleep compared to healthy controls, according to the study, "Functional Dyspepsia: A Risk Factor for Disordered Sleep," which also found that women with functional dyspepsia were 2.3 times more likely to have disordered sleep than men with this same condition. While gender tended to be associated with disordered sleep, age, tobacco and alcohol use was not a factor. The study also found that mental and physical factors were related to disordered sleep in patients with functional dyspepsia.

Routine exercise, for instance, appeared to decrease the likelihood of a patient suffering from sleep disorders. Functional dyspepsia patients also had higher scores for anxiety and depression, according to the study, suggesting that depression may be a contributing factor to functional dyspepsia symptom generation.

"Fatigue changes the sensation for pain, said Brian Lacy, M.D., Ph.D., associate professor of medicine, Dartmouth Medical School who presented the results of the study. "The key finding here is that disordered sleep may affect nerve function in upper GI tract which could lead to worsening dyspepsia, creating a vicious cycle leading to more pain and more insomnia," said Dr. Lacy. He added that, "future clinical trials for functional dyspepsia should include validated measures of sleep, as improvements in functional dyspepsia symptoms may be mirrored by improvements in sleep."

Esomeprazole Reverses Driving Impairment in GERD Induced Sleep Disorders

GERD‐induced sleep dysfunction has a previously unrecognized and significantly adverse affect on simulated driving performance, which improved with esomeprazole, according to the results of another study, "GERD‐Induced Sleep Disorders and a Reversible Driving Impairment with Esomeprazole‐A Prospective Pilot Study."

Dr. David A. Johnson, Chief of Gastroenterology and Professor of Medicine at Eastern Virginia Medical School in Norfolk, Va., presented the findings from this prospective‐pilot study that evaluated 11 healthy patients with well‐established GERD with nocturnal symptoms.

Testing was done in a validated commercial driving simulator that responds to driver inputs (steering, throttle, brake) and generates realistic roadway images. Driving performance (standard deviation of lane variation SDLP) was compared across six consecutive 10‐minute driving periods while subjects were on and off the drug.

According to the study, SDLP increased over time (p=0.0002) and improved with esomeprazole. Patients on esomeprazole had an overall average 62.5 percent decrease in the number of sleep disordered nights vs. a 9.5 percent decrease without the drug. The Epworth Sleepiness Scale, used to determine the level of daytime sleepiness, decreased to 5.9 and 3.5 from 7.9 and 2.5 and GERD symptom score decreased from 2.10 to 0.33.

"The improved ESS score suggests that reduced sleepiness contributed to improved performance," said Dr. Johnson. "We know that GERD impairs sleep quality and next day function as measured by quality of life and work productivity assessments. Furthermore, sleep dysfunction (such as sleep apnea) has been linked to impaired psychomotor function including worsening driving simulator performance.

Therefore, appropriate treatment for patients with GERD and nocturnal symptoms may have potentially new and life‐saving implications."

Dr. Johnson also noted that further prospective blinded controlled trials are warranted to validate these findings.

Baclofen Decreases Reflux, Improving Sleep Quality for Nighttime Heartburn Sufferers

Nighttime heartburn sufferers also may get relief — and better sleep quality, from the muscle‐relaxant and antispastic drug, baclofen, according to results of another new study, "Baclofen Decreases Reflux and Improves Sleep Quality in Individuals with Nighttime Heartburn."

While baclofen has been shown to reduce episodes of GERD, this new study found that in addition to reducing the number of reflux events during sleep, baclofen significantly improved several measures of sleep in patients with documented GERD and sleep disturbances.

"About 70 percent of individuals who have GERD also suffer from nighttime heartburn, and 40 percent of those people say they experience disturbed sleep at night," said study co‐author Dr. William Orr, president and CEO of the Lynn Health Science Institute and a clinical professor of medicine at the University of Oklahoma Health Sciences Center. "They don't feel good the next day and they don't perform as well."

Approved by the FDA in 1977, bacolfen is typically used by neurologists to treat uncontrolled movements, such as shakes and tremors. The drug inhibits nerve activity within the part of the brain that controls the contraction and relaxation of skeletal muscles.

"In this study, we found that bacolfen significantly reduces the amount of waking which occurs after the onset of sleep," said Dr. Orr. "Baclofen addresses the physiological causes of reflux, by preventing the relaxation of the lower esophageal sphincter and preventing the stomach acid from entering the esophagus. Few drugs inhibit the occurrence of reflux and 40 to 50 percent of those taking PPIs don't get satisfactory relief, especially at nighttime,"

Baclofen reduced the number of reflux events compared to a placebo (4 events vs. 1.3). Patients on baclofen also had more sleep time (434 minutes vs. 379 minutes) and greater sleep efficiency (91 percent vs. 79 percent), according to the study. "The results of this study suggest that baclofen could be a useful adjunct therapy to proton pump inhibitors in patients with nighttime heartburn and sleep disturbance," said Dr. Orr.

A study in the Oct. 15 issue of the Journal of Clinical Sleep Medicine found that adults with fibromyalgia had a much higher prevalence and risk of restless legs syndrome than healthy controls. The study suggests that treating RLS may improve sleep and quality of life in people with fibromyalgia.

Results show that the prevalence of restless legs syndrome was about 10 times higher in the fibromyalgia group (33 percent) than among controls (3.1 percent). After statistical adjustments for potential confounders such as age, gender and ethnicity, participants with fibromyalgia were 11 times more likely than controls to have RLS (odds ratio = 11.2). As expected, considerable sleep disruption was reported by participants with fibromyalgia using the Pittsburgh Sleep Quality Index, Insomnia Severity Index and Epworth Sleepiness Scale. In the fibromyalgia group these sleep problems were more severe among people who also had RLS.

"Sleep disruption is common in fibromyalgia, and often difficult to treat," said contributing author Dr. Nathaniel F. Watson, associate professor of neurology at the University of Washington in Seattle, Wash. "It is apparent from our study that a substantial portion of sleep disruption in fibromyalgia is due to restless legs syndrome."

The research team led by Dr. Watson and lead author Dr. Mari Viola-Saltzman of Loyola University Medical Center in Maywood, Ill., studied 172 people with fibromyalgia who had a mean age of 50 years; 93 percent were female. They were compared with 63 healthy controls who had a mean age of 41 years.

Fibromyalgia was identified by self-report or review of the medical records, and it was confirmed on examination according to published guidelines regarding the presence of pain that is chronic and widespread. Pain was assessed by subjective report and by objective measurement with a dolorimeter, a spring-loaded gauge that is used to apply standardized rates of pressure to tender points on the arms and legs.

According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, fibromyalgia can cause significant pain and fatigue. It is estimated to affect 5 million Americans age 18 or older, and between 80 and 90 percent of those diagnosed with fibromyalgia are women. The causes of fibromyalgia remain unknown.

Restless legs syndrome was diagnosed using a self-administered, validated questionnaire. RLS is a sleep-related movement disorder that involves an urge to move the legs that is usually accompanied or caused by uncomfortable and unpleasant sensations in the legs. This urge begins or worsens during periods of rest or inactivity, is partially or totally resolved by movement, and worsens or only occurs at night. RLS occurs 1.5 to two times more commonly in women than in men.

Watson noted that treating restless legs syndrome may be one of the keys to reducing fatigue and improving quality of life in people with fibromyalgia. RLS often can be successfully treated with a medication such as pramipexole or ropinirole.

"Since restless legs syndrome is a treatable condition, diagnosing and treating RLS in fibromyalgia patients has the potential to improve their sleep," Watson said.

According to the authors, the cross-sectional nature of the study did not allow for an examination of causality. However, several aspects of the two syndromes suggest a logical overlap. Both disorders involve sensory abnormalities, and a similar pathophysiology of the system that regulates the neurotransmitter dopamine has been proposed for both syndromes. Furthermore, restless legs syndrome may be induced by antidepressants, which are a common treatment for pain and depression in fibromyalgia. Also, exercise has been shown to improve the symptoms of both syndromes.

The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and by the National Fibromyalgia Research Association.

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Journal Reference:

1. Mari Viola-Saltzman, Nathaniel F. Watson, Andy Bogart, Jack Goldberg, Dedra Buchwald. High prevalence of restless legs syndrome among patients with fibromyalgia: a controlled cross-sectional study. Journal of Clinical Sleep Medicine, 2010; 6 (5): 423-427 [link]

With the help of tiny, see-through fish, Stanford University School of Medicine researchers are homing in on what happens in the brain while you sleep. In a new study, they show how the circadian clock and sleep affect the scope of neuron-to-neuron connections in a particular region of the brain, and they identified a gene that appears to regulate the number of these connections, called synapses.

"This is the first time differences in the number of synapses between day and night and between wake and sleep have been shown in a living animal," said Lior Appelbaum, PhD, co-first author of the study, which will appear in the Oct. 6 issue of Neuron. He said further studies using the imaging method he and his colleagues developed could shed more light on how our brain activities vary according to time of day.

Appelbaum, who is now a principal investigator in a lab at Bar-Ilan University in Israel, spent five years conducting the work while in the lab of Emmanuel Mignot, MD, PhD, professor of psychiatry and behavioral sciences. Mignot, who also directs the Stanford Center for Sleep Sciences and Medicine, is senior author of the paper; the other first author is Gordon Wang, PhD, a postdoctoral scholar in molecular and cellular physiology.

Why we need to sleep and how, exactly, sleep is restorative are two big, unanswered questions in biology. Knowing that brain performance changes throughout the day, researchers believe that daily cycles and sleep regulate "synaptic plasticity" — the ability of synapses to change strength and even form and erase. And they theorize that nighttime changes in the number and strength of synapses help recharge the brain which, in turn, benefits memory, learning and other functions.

As the researchers note in their paper, daily cycle-related changes in the number of neuron-to-neuron connections hadn't previously been shown in a living vertebrate, and the "molecular mechanisms of this type of synaptic plasticity are poorly understood." So they turned to the zebrafish, a small aquarium pet, for help.

Like humans, zebrafish are active during the day and sleep at night — something that researchers in Mignot's lab discovered in previous research. Larvae of the handy little fish also happen to be transparent, enabling researchers to look directly at the animal's neuronal network. "This can't be done in any other vertebrate animal," said Mignot, who is also the Craig Reynolds Professor of Sleep Medicine, adding that his group was aided by the imaging expertise of co-author Stephen Smith, PhD, professor of molecular and cellular physiology, and his lab.

For this study, the researchers used a fluorescence-imaging technique to monitor neural activity in the specific region of the brain that regulates sleeping and waking. With their technique, they were able to watch synapses within individual hypocretin neurons, and they showed that the number of these connections fluctuated between day and night.

Appelbaum noted this is the first time rhythmic changes in synapse numbers have been observed in the brain of a living vertebrate. The work also, Mignot said, further demonstrates the brain's ability to reorganize and adapt to changes. "It gets ready for new activity by telling the neurons they have to shut down synapses during this time of day but increase them at other times of the day," he said.

The researchers determined that the differing number of synapses between day and night was primarily regulated by the body's internal clock but was also affected by behavior — for instance, how much sleep the fish got. They also identified a gene, NPTX2b, that appears to be involved in regulating the rhythmic changes in synapses. "It's one actor in an unknown mechanism," said Appelbaum, explaining it's unlikely that only one gene is involved, but its identification gets researchers that much closer to understanding the process.

Appelbaum said he considers the imaging method itself one of the strongest points of the paper, and by using the technique developed in this study, investigators can image synaptic plasticity in other neuronal systems — circuits — of the zebrafish to expand on these findings. "With these techniques, we can look at other areas of the brain, such as the one in charge of memory, to see how sleep cycles affect synapses," he said, adding that he doesn't expect to see the same results in every part of the brain.

"Those changes are likely circuit-dependent," he explained, saying that synaptic plasticity in memory circuits might prove to be more affected by behavior, such as sleep, than by the circadian clock (the opposite of what was found in hypocretin neurons). Knowing this, he said, could help identify which regions of brain are most affected by waking and sleeping and further uncover what happens when we slumber.

Other study authors are Tohei Yokogawa, PhD, then a graduate student in Mignot's lab; research assistant Gemini Skariah; and Philippe Mourrain, PhD, a senior research scientist in psychiatry and behavioral sciences, who co-directed the work.

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Journal Reference:

1. Lior Appelbaum, Gordon Wang, Tohei Yokogawa, Gemini M. Skariah, Stephen J. Smith, Philippe Mourrain, Emmanuel Mignot. Circadian and Homeostatic Regulation of Structural Synaptic Plasticity in Hypocretin Neurons. Neuron, 2010; 68 (1): 87-98 DOI: 10.1016/j.neuron.2010.09.006

A study in the Oct. 1 issue of the journal Sleep found that getting too little or too much sleep in early pregnancy is associated with elevated blood pressure in the third trimester. The study suggests that improving prenatal sleep hygiene may provide important health benefits.

Results show that the mean systolic blood pressure in the third trimester was 114 mm Hg in women with a normal self-reported nightly sleep duration of nine hours in early pregnancy, 118.05 mm Hg in women who reported sleeping six hours or less per night, and 118.90 mm Hg in women with a nightly sleep duration of 10 hours or more in early pregnancy. After adjustments for potential confounders such as age, race and pre-pregnancy body mass index, mean systolic blood pressure was 3.72 mm Hg higher in short sleepers and 4.21 mm Hg higher in long sleepers. Similar results also were found for diastolic blood pressure.

"Both short and long sleep duration in early pregnancy were associated with increased mean third trimester systolic and diastolic blood pressure values," said principal investigator and lead author Dr. Michelle A. Williams, professor of epidemiology in the School of Public Health at the University of Washington and co-director of the Center for Perinatal Studies at Swedish Medical Center in Seattle, Wash.

The study also found an association between sleep duration and preeclampsia, a condition that involves pregnancy-induced hypertension along with excess protein in the urine. The risk of developing preeclampsia was almost 10 times higher (adjusted odds ratio = 9.52) in very short sleepers who had a nightly sleep duration of less than five hours during early pregnancy. Overall, about 6.3 percent of participants were diagnosed with either preeclampsia or pregnancy-induced hypertension without proteinuria.

"If our results are confirmed by other studies, the findings may motivate increased efforts aimed at exploring lifestyle approaches, particularly improved sleep habits, to lower preeclampsia risk," said Williams.

According to the National Heart, Lung, and Blood Institute, systolic blood pressure — the top number in a blood pressure reading — is the force of blood in the arteries as the heart beats. A systolic blood pressure reading is considered to be "high" if it is 140 or more millimeters of mercury.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development reports that preeclampsia is a syndrome that occurs after the 20th week of pregnancy. It should be monitored closely by a medical professional because it can have a severe impact on the health of the mother and her baby.

The study involved 1,272 healthy, pregnant women who completed a structured interview at 14 weeks gestation, on average. Sleep duration in early pregnancy was evaluated by the question, "Since becoming pregnant, how many hours per night do you sleep?" Only about 20.5 percent of women reported a sleep duration of nine hours per night, which was used as the "normal" reference category because prior research indicates that pregnant women tend to have longer sleep duration patterns. About 55.2 percent of women reported sleeping seven to eight hours per night, 13.7 percent slept six hours or less and about 10.6 percent slept 10 hours or more.

After delivery, data on maternal blood pressures at routine prenatal care visits were abstracted from participants' medical records, providing an average of 12 blood pressure values for each participant. Women with pre-gestational chronic hypertension were excluded from the study. Mean systolic blood pressures were 111.8 mm Hg and 111.4 mm Hg in the first and second trimesters, and 114.1 mm Hg in the third trimester.

According to the authors, a number of mechanisms by which habitual short sleep duration may lead to increased blood pressure have been proposed. Because blood pressure is known to dip by an average of 10 to 20 percent during sleep, short sleep durations may raise the average 24-hour blood pressure and heart rate. This may lead to structural changes that gradually raise the pressure equilibrium of the entire cardiovascular system. Sleep restriction also may produce abnormalities in the levels of hormones such as endothelin and vasopressin, which play an important role in the cardiovascular system. The authors suspect that the association between long sleep duration and elevated blood pressures may be related to unmeasured confounders such as obstructive sleep apnea, depression or insulin resistance.

Williams noted that this study is the first step at filling an important gap in the scientific literature. Because most sleep studies exclude pregnant women, little is known about how insufficient sleep during gestation contributes to increased risks of medical complications of pregnancy.

"Moving forward, large-scale sleep studies should include pregnancy cohorts so that health care providers and mothers-to-be can more fully appreciate the health risks of insufficient sleep," she said.

Williams advises pregnant women and women who are planning to become pregnant to develop healthy habits that promote sufficient sleep. The tips she suggested include:

• Establishing a consistent sleep schedule
• Following a relaxing bedtime routine
• Creating a comfortable sleep environment
• Keeping technological distractions such as the TV and computer out of the bedroom
• Eating at least two to three hours before bedtime
• Exercising regularly during the day
• Avoiding caffeine and alcohol before bedtime and giving up smoking

The study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health.

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Journal Reference:

1. Michelle A. Williams et al. Associations of early pregnancy sleep duration with trimester-specific blood pressures and hypertensive disorders in pregnancy. Sleep,