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Transcript: NICHD Research Perspectives—November 30, 2012

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Announcer: From the Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health, welcome to another installment of NICHD Research Perspectives. Your host is the Director of the NICHD, Dr. Alan Guttmacher.

Dr. Alan Guttmacher: Hello, I’m Alan Guttmacher. Thanks for joining us for another in our monthly series of podcasts from the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health.

Our guests today are Drs. David Klein, Caroline Signore, Lynne Haverkos, and Paul Albert. We’ll be talking with them about their recent presentations during one of our periodic programs for NICHD staff at which our scientists summarize what they know about a field of research as well as outline opportunities for new related research and health advances. The topic of this recent discussion, which we will be reprising briefly here, was “Sleep: the ABCs of Zs.”

Sleep is a critical determinant of health and well-being and is a basic requirement for infant, child, and adolescent development as well as for healthy aging. Pregnant women struggle to get restful sleep, and new parents are notoriously sleep-deprived. Poor sleep negatively affects productivity and interpersonal relationships and can increase errors and mishaps daily. More than 25 percent of U.S. adults report insufficient sleep or rest at least 15 out of every 30 days.

We don’t fully understand sleep, but after many years of research, we’ve been able to learn a lot about it. We do know that it’s not just a simple phenomenon of the brain shutting down. Rather, it appears to be a complex condition encompassing five distinct stages, each associated with a distinct pattern of electrical activity in the brain.

In stage 1, your eyes close, breathing becomes more regular, and eye movements slow. Although you’re less aware of what’s going on around you than when you’re awake, you can be easily awoken. This stage may come on unexpectedly while watching television, for example, or as many of us know, while trying to follow a technical lecture. This stage lasts for only about 5 or 10 minutes at a time—about 5 percent of the total amount of sleep time for a healthy adult.

In Stage 2, heart rate slows, breathing becomes even more regular, body temperature drops slightly, and muscles relax. The sleeping person is even less aware of his or her surroundings than in stage 1, but can still be easily awakened.

Stages 3 and 4 are sometimes referred to as “slow wave” sleep because brain waves are slower and more regular during these stages than in the first two stages. It’s much more difficult to wake someone up during stages 3 and 4. Persons who are awakened during these stages—by a ringing telephone perhaps—are likely to be disoriented and not fully comprehend what’s going on. The next day they may not even remember having had the telephone conversation.

The fifth stage is known as REM sleep. REM stands for “rapid eye movements.” In contrast to the first four stages, the brain is very active during REM sleep with brain activity patterns resembling those seen when awake. But although the brain is very active, the sleeping person is unaware of their surroundings. This is the stage when most dreaming occurs. Brief, dream-like images may flicker through the brain during the other sleep stages, but it is in REM sleep that complicated, activity-driven sequences that we think of as dreams occur. Although the brain becomes more active during REM sleep, the body becomes much less active. A person may twitch slightly, but for the most part, movement stops. In fact, the sleeping patient is often unable to move and enters a stage resembling paralysis.

These stages repeat themselves throughout the course of the night (assuming that is when you’re sleeping, an issue we may return to), for a total of 4 to 6 complete cycles each night.

Our first guest today is Dr. David Klein, Chief of the Section on Neuroendocrinology, in our intramural program here at NICHD. His research focuses on understanding the pineal gland, a brain structure that performs a number of functions, including regulating the body’s cycles of sleep and waking. Dr. Klein, could you tell us please, what is known about the genes regulating sleep?

Dr. David Klein: Well, we view sleep as being composed of two operative organizations. One has a job of telling us when we have to sleep, and the other one has a job of telling us how much sleep we need. There’s been incredible advances made in understanding the genes involved in determining when we want to sleep, when we should be sleeping, and this body of work has resulted in the identification of a group of genes, which are referred to as the clock genes. And these genes work together to give our bodies a 24-hour rhythm. Whereas there’s been fabulous advances made in understanding this mechanism, our advances in understanding what controls the amount of sleep we need have not been as impressive. And there is significant amount of progress left to be done in that area. However, going back to the clock, our intimate knowledge of the genes that regulate the biological clock and our biological timing are well identified. In fact, now human biologists are searching for mutations in the genes associated with a disease, mental disease, and timing and dysfunction of the sleep system. So, whereas one part of the system, this two-part when and how much system, the when part is really well understood on a genetic basis, the how much, well, that’s still a work in progress.

Dr. Guttmacher: Thanks, David. I know the pineal gland is very important to sleep and part of that’s because it produces melatonin. Can you tell us what role that hormone plays in the sleep process?

Dr. Klein: Yeah, it goes back to the—the answer goes back to both areas of this system that regulates sleep, to the best of our knowledge. Both are targets for melatonin. The best studied and the most sensitive system is the clock; and in our brains, the clock is located in a small part of the hypothalamus, a small part of the brain. And that part of the brain is scientifically called the suprachiasmatic nucleus, but more popularly we refer to it as the mind’s clock, the mind’s clock. That mind’s clock is really fabulous because it controls timing of all biological processes that go on in our bodies—quite impressive. And melatonin’s receptors, those molecules that are able to pick up and sense the presence of melatonin, those receptors are abundant in that area of the brain, and it is generally accepted that those receptors mediate one of the powerful effects of melatonin, which is to help reset the clock so melatonin acts something like that little part of your watch that allows you to advance and reset the hands of the clock. So that’s one part of the actions of melatonin, resetting the clock. The second part is that melatonin does have some sleep-inducing effects: they’re very subtle, but in some people the effects are clear. And it’s because of this combined effect, we think—of both controlling when we sleep and how much we sleep—melatonin’s used popularly by individuals who don’t receive strong cues to reset the clock. There are blind people—now blind people lack the ability to detect when it’s light and dark outside, but melatonin is almost as good as light, and melatonin can help reset the clock. So with blind people it’s been found that although their rhythms without melatonin could be what we’d call sloppy—not entirely integrated and coordinated with environmental lighting—if they take melatonin on a regular basis, they can entrain themselves to a 24-hour day. More interestingly, this has been picked up and used in a, I’d say, nonmedical way by families who have blind children and also children whose sleep patterns are disturbed in association with diseases. And in many cases it’s been found that the parents have been successful in regularizing the sleep patterns of the individual children. This is not only important to this one individual, the child, but if a family can coordinate the sleep of the child with the rest of the family, then that child will not disturb family schedules, which can have devastating effects on family structure and family function. So, melatonin, certainly, can be used to improve sleep patterns.

Dr. Guttmacher: Thanks very much, David. I think we should stress obviously that any family wants to think about possibly using melatonin for themselves and particularly for their children, they should definitely talk to pediatrician or family physician before thinking about doing that, just as you would with the use of any medication, whether by prescription on nonprescription with your children. That’s certainly something you’d want to talk over with your physician before you went ahead and did it. Our next guest is Dr. Caroline Signore, of NICHD’s extramural Pregnancy and Perinatology Branch. In her recent presentation to our staff, which she called, “Snooze for Twos,” Caroline described how the physiological changes that occur during pregnancy can affect breathing and, by doing so, affect sleeping patterns. Caroline, I know there’s a lot of ground to cover, but can you tell us what pregnant women should know about sleep-disordered breathing?

Dr. Caroline Signore: Sure. Well, it’s very common for pregnant women to have trouble getting a good night’s rest, and as many as 9 in 10 women will describe trouble sleeping at some point during their pregnancy. There are many bodily changes that occur during pregnancy and most of them can affect sleep amount and quality. So, for example, high hormone levels that begin early in pregnancy can disrupt the stages of sleep, Dr. Guttmacher, that you were describing earlier. Especially in late pregnancy, common discomforts can make it quite difficult for women to fall asleep or stay asleep and remain comfortable, and these include heartburn, backache, leg cramps, even fetal movements in the night can keep women awake. A very common problem is that pressure from the growing fetus compresses the urinary bladder, and women will find themselves having to get up one or more times per night to use the bathroom. And this can be very disruptive to a night’s sleep. But importantly, pregnancy also changes breathing, and this is an issue that’s getting a lot of attention these days. So pregnancy hormones cause tissues in the throat and the nasal passages to swell or become edematous, and it makes it a little more difficult for air to move in if the passageway is narrowed just a bit. Also the growing fetus compresses the bases of the lungs and decreases the amount of air the lungs can actually hold. Pregnancy hormones also stimulate women to try and take deeper breaths in a regular basis. If you put all this together, we see that pregnant women are a little bit more likely to develop what we call sleep-disordered breathing. This is a term describing certain types of breathing disturbances that occur during sleep. So, snoring—that we’re all familiar with—is a very common form of sleep-disordered breathing and studies show that indeed up to 40 percent of women will start snoring during their pregnancies. Another form of sleep-disordered breathing is called obstructive sleep apnea. This is a condition in which during sleep the tissues of the throat and airway collapse and temporarily block the flow of air into the lungs. Breathing essentially stops for a few moments but the body senses that this has occurred, senses that oxygen levels may be getting low, and alerts the person to wake up; the brain sends out a signal to cause an arousal and a person will wake up and perhaps cough or gasp and resume normal breathing. Now this cycle of obstruction and arousal and obstruction and arousal can occur dozens or even hundreds of times per night, causing quite a lot of disruption in the night’s sleep. We know that obstructed sleep apnea occurs in about 5 percent of women during their childbearing years. We don’t know quite as much about how often it occurs in pregnant women, but one study showed that as many as 15 percent of pregnant women are affected with obstructive sleep apnea. How would you know if you had obstructive sleep apnea? Well, snoring is the most prominent feature, and typically people with apnea will snore heavily and loudly and very frequently at least three to four times per night. People with sleep apnea will also wake feeling tired and feel that they’ve had nonrestful sleep and struggle with excessive sleepiness during the day. This is a cardinal sign of sleep apnea, which is also more common in people who are overweight or obese. The good news is that there is treatment for sleep apnea. This is through something called continuous positive airway pressure, or CPAP for short, and this is a treatment with an apparatus worn on the face that gently holds the airway open with a positive flow of air. This is safe to use in pregnancy, so there are treatments available.

Dr. Guttmacher: Caroline, I’ve heard you mention before a possible connection between sleep disorders during pregnancy and blood pressure. Can you tell us about that?

Dr. Signore: Sure. This is a fairly new area of investigation for pregnancy and sleep researchers. It’s been known for some time that sleep-disordered breathing among nonpregnant adults is associated with increased risk of high blood pressure, diabetes, and other health problems. What we also know is that if you treat the breathing problem with CPAP, blood pressure improves, diabetes improves, and there are quite dramatic turnarounds possible. Well, we know that similar problems of hypertension and diabetes occur in pregnancy, and those are conditions that we call preeclampsia or gestational diabetes. So researchers are quite interested to learn whether there is a link between sleep-disordered breathing during pregnancy and these complications, and some studies are showing that this may indeed be the case. One study, for example, showed that women who started snoring heavily during their pregnancies were twice as likely to develop preeclampsia. We don’t know yet if this will be confirmed in other studies, and we don’t yet know if treatment with CPAP in pregnancy could prevent or decrease the severity of these complications.

Dr. Guttmacher: Thank you, Dr. Signore. Our next guest is Dr. Lynne Haverkos, of NICHD’s extramural Child Development and Behavior Branch. Her presentation to staff, titled “You Snooze, You Win,” detailed the many changes in sleep patterns that occur throughout childhood and adolescence. Lynne is out of the office today, so she’s joining us by phone. Lynne, you described a lot of studies showing benefits to learning when children sleep well and problems that occur when they don’t sleep so well. Can you tell us about some of this research and how parents and caregivers can assure that children are getting the most out of each night’s sleep?

Dr. Lynne Haverkos: Certainly, I’ll be glad to. Sleep is especially important to children’s learning. For example, research on infants has shown that even as infants sleep, they are processing information and forming memories—essentially learning. In one study, researchers paired a sound or tone with a puff of air to the eyelids of sleeping infants. The sleeping infants squeezed their eyelids in response to the puff of air. After a few trials, they squeezed their eyelids just in response to the sound without the air puff. This study was funded by our institute, by the way. Another study found that the kind of stimulus made a difference. Sleeping infants made the connection faster when they heard a voice rather than a musical tone. Newborns sleep about 16 to 18 hours per day with roughly equal amounts during the day and night. As they mature, they learn to consolidate sleep by gradually decreasing the sleep during the day and increasing the nighttime sleep. Researchers found that the day-to-night sleep ratio captures developmental change better and is more strongly correlated with cognitive outcomes than total sleep duration. For example, a study of twins found that children who were successfully consolidating sleep at 6 and 18 months had better language skills up to 3½ years later. This suggests that sleep consolidation may influence the language learning process. In the past decade, research has shown that sleep plays an important role in learning. Sleep deprivation can impair learning and memory for both procedural memory, which involves skills and problem-solving, and declarative memory, which involves recalling facts. A study of second- and third-graders showed that children with increased daytime sleeping over a 3-year period had little growth in verbal comprehension when they were compared to classmates who were less sleepy. This is important because children who are sleepy during the day are more likely to have long-term impairments during those critical stages of learning. Each year of sleepiness adversely interferes with the development of cognitive abilities because learning builds upon fundamental knowledge of children who miss out on the fundamentals can fall behind and maybe later face learning disabilities. Research has shown that both sleep quality and quantity influence daytime sleepiness, which can affect learning and behavior. Children and adolescents need about 9 hours of sleep each night, but routinely get less than 8 hours. About 20 to 50 percent of children and adolescents report daytime sleepiness, which can result in reduced alertness and can compromise daytime functioning. Neural imaging studies have shown that even short-term sleep loss can impair functions such as attention, divergent thinking, language, decision-making, memory, and response inhibition. It’s well known that adolescence is the time when many individuals don’t get enough sleep. This may be because of the biological changes that occur as they mature. Their circadian rhythm-- their internal clock, that we’ve heard about before-- may delay their falling asleep. And social pressures—like talking on the phone,  watching TV or playing video games—and academic pressures—like homework—can keep kids from getting to sleep on time. When adolescents go to bed late but have to get up early for school, many get insufficient sleep and have to sleep late on weekends to catch up. A number of negative consequences can result from this long-term sleep loss, including poor academic achievement, mood difficulties, and an increase in risky behaviors. Caroline mentioned the obstructive sleep apnea, and that can occur in children as well as adults. And it’s been associated with deficits of memory, learning, and executive function in children. And in one animal model of obstructive sleep apnea, marked effects on the brain and on learning were observed in a period that was equivalent to early childhood. Sleep-disordered breathing is another condition that has been associated with impairments in cognitive function. In a study by Ron Chervin, supported by the NICHD, children scheduled to have tonsils removed to correct sleep-disordered breathing were compared to kids the same age but who were scheduled for other types of surgery. The children scheduled for tonsillectomy were found to be more hyperactive, inattentive, sleepy, and more likely to be diagnosed with ADHD than those kids in the control group. But 1 year after the surgery children whose sleep-disordered breathing was corrected by tonsillectomy had no significant differences in measures of attention, hyperactivity, sleepiness, and diagnoses of ADHD when compared to the control group. And it’s studies like these that indicate that sleep is essential for optimizing cognition, memory, learning, and behavior regulation. So in response to your question about what can parents do to help their children get adequate sleep, I have several suggestions. Parents can start early when their kids are young by establishing enjoyable bedtime routines, and these could include things like brushing teeth, taking a bath, reading a book or a story, and having regular bedtime hours. It’s helpful also to have a quiet, cool, dark bedroom for comfortable sleeping. Parents can establish a lights-off policy and avoid having a TV in the bedroom because that causes bedtime distractions. No caffeinated drinks at bedtime, and this includes soda and soft drinks as well as coffee and tea. So if parents do all these things, they could potentially improve their children’s sleep and, therefore, their learning.

Dr. Signore: Lynne, could you describe the benefits of napping for small children in addition to giving parents a chance to recover their energy for when the children wake up?

Dr. Haverkos: Sure, Caroline. There are several reasons why naps are important. First, newborns and infants need a great deal of sleep in the early years. Naps throughout the day add to that total daily sleep time that they need. Second, napping allows memories to be processed, sorted, and stored for easy retrieval and therefore aids learning. It’s interesting to note that some college students and adults take what we would call power naps, and that seems to help refresh them during the day. And according to the National Sleep Foundation, a short nap of 20 to 30 minutes can help to improve mood, alertness, and performance. Thanks for asking.

Dr. Guttmacher: And, Lynne, thank you for that description about sleep in children and adolescents. For any of us who have children and adolescents or have had them even were ourselves children and adolescents, that was very interesting and useful information. Our next guest is Dr. Paul Albert of NICHD’s Division of Epidemiology, Statistics and Prevention Research. Our first three guests reviewed the scientific literature and told us about what the research has informed us about sleep. Dr. Albert is among those breaking new ground in understanding sleep. His field is statistics, and he and his colleagues are planning a 7-year longitudinal study of about 3,000 youth, beginning in 10th grade, called the NEXT Study. This study seeks to identify the health risks associated with adolescence and early adulthood and find ways to remediate them. One component of the study is examining sleeping patterns in adolescents. Paul has looked at the challenges of trying to track sleep patterns in an age group famous, if not infamous, for irregular sleeping habits, as Dr. Haverkos already mentioned to us. But Paul, before you tell us about those challenges, can you tell us first why do we need to study sleep in adolescents to begin with?

Dr. Paul Albert: Thank you, Dr. Guttmacher. Increasingly many adolescents go to sleep very late and have irregular sleeping patterns. I have a 20-year-old who in the summer goes to bed very late, wakes up relatively early, but then takes many naps during the day. And of interest to me as a parent but also, in general, is to examine whether sleeping patterns are predictive of subsequent health risks in adolescents early adulthood. For example, maybe those adolescents or individuals with certain sleeping patterns in the tenth grade, are more likely be substance abusers in later adolescence or early adulthood. Measuring sleep in this population of teenagers is difficult since often one uses self-reports, which, if anyone’s had adolescents they know would probably be not very reliable. A component of the NEXT study, called the NEXT Plus study, is a substudy with 550 participants, half being obese and half having normal weight, which were followed extensively on longitudinal assessments over each of the 7 years—will be followed—of biomarkers, blood pressure, dietary recalls, driving performance, and assessments of sleep. In terms of sleep, both self-reports are measured at yearly intervals over 2-week periods. And also an ActiWatch® is worn, and the idea is the ActiWatch® is worn on their hand for 7 days on and each of the follow-up years, and the watch measures activity counts in 30-second epochs during the day. So what’s of interest now is to see if we can come up with good measures of sleep. We know that self-reports are unreliable, and what we want to come up with is good measures. Maybe what we can do is combine different sources together such of the activity watch and self-reports and maybe the light in the room, the ActiWatch® also measures the light in the room. And what we’ve been doing from a statistical point of view is trying to combine these measurements. We use an approach called hidden Markov model, and the idea is what’s hidden is the actual sleep pattern. We don’t really see the true sleep pattern. What we see are noisy measures of it, meaning the self-report, the activity measured during the day and night, and maybe the light in the room throughout the day. So what these hidden Markov models do is try to reconstruct the true process from these noisy measurements. And they’ve been used in lots of different areas, not in sleep, but they’ve been used in genetics, copy number variation, and also even in seizure frequency and trying to model seizure frequency in patients with epilepsy. So that’s the kind of work we’re doing to try to really come up with good measures of sleep so we can look—in the future be able to summarize those sleep patterns in a reliable way to look at the effect of sleep on subsequent behavioral and other outcomes in early adulthood.

Dr. Guttmacher: Talking about sleep patterns and outcomes in early adulthood, can you tell us anything about sleeping patterns in obesity?

Dr. Albert: So that’s a good question. We had a summer student, a biostatistics Ph.D. student, last summer who came, and what their interest was, was on comparing the sleep and activity patterns basically between obese and nonobese teenagers. And to answer this question, we’ll need a new statistical methodology, and the idea is we wanted to compare the circadian patterns in the frequency of these counts and before I measured the ActiWatch®, they measured these counts in 30-second epochs, 30-second periods, all through the day. And we want to see how those patterns change over a 7-day period for the two weight groups. And what we did is we developed a method where we can actually compare the two curves, if you think of the circadian patterns in terms of three features, which I think made important biological sense. One of them is the overall level of activity, one of them is the amplitude, which is the lowest point of the highest point in the curve, and the other is a shift, a phase shift, where you see the circadian pattern just moving over one way or the other. And what we’ve found is after adjusting for a different demographic effect—our model allows us to do that—different demographic and other education and other factors, what we found is the difference between obese and nonobese teenagers was not so much the overall level of activity, but it was much more the phase shift. Adolescents who were obese seem to go to sleep later and wake up later than their nonobese counterparts. Now, we’re currently really interested in other factors, and in statistics we often focus on the mean, the average curve, but what we think may be going on is it may be an individual variation, or a variation across for the same person. So individuals who are very activity patterns that are actually changing over the days may be at more risk for certain kinds of outcome, and we are now looking at that. And we’ll be looking at patterns and how these activity patterns in obese and nonobese teenagers, how they change over time and in each of the groups—whether they predict future poor outcomes in early adulthood.

Dr. Guttmacher: Thank you, Paul, I’d like to thank Drs. Klein, Signore, Haverkos, and Albert for joining us today and for sharing with us some of research on this truly fascinating topic. I found it particularly fascinating either in spite of or because of the fact that I woke up at 3 a.m. this morning and wasn’t able to go back to sleep. So I suspect I’m not alone in our listening audience to deal with it that way. So thanks, it’s been quite interesting. I’d also like to thank all of our listeners for joining us and for your interest in our work here at NICHD.

For more information on any of today’s topics and many related topics, visit www.nichd.nih.gov. And while I’m mentioning that website, a special note about sleep for all of you with newborns or infants in your families, please visit that website, www.nichd.nih.gov, and enter “safe to sleep”—safe to sleep—in the search engine to find out how you can make sure that your baby is sleeping as safely as possible. That’s www.nichd.nih.gov and safe to sleep in the search engine.

I’m Alan Guttmacher, and I hope you will join us for more NICHD podcasts as we post them on our website each month.

Announcer: This has been NICHD Research Perspectives, a monthly podcast series hosted by Dr. Alan Guttmacher. To listen to previous installments, visit nichd.nih.gov/researchperspectives. If you have any questions or comments, please email NICHDInformationResourceCenter@mail.nih.gov.

Back to Research Perspectives.

Last Updated Date: 12/12/2012
Last Reviewed Date: 12/12/2012
Vision National Institutes of Health Home BOND National Institues of Health Home Home Storz Lab: Section on Environmental Gene Regulation Home Machner Lab: Unit on Microbial Pathogenesis Home Division of Intramural Population Health Research Home Bonifacino Lab: Section on Intracellular Protein Trafficking Home Lilly Lab: Section on Gamete Development Home Lippincott-Schwartz Lab: Section on Organelle Biology