Insomnia not purely psychological condition: Insomnia genes found

An international team of researchers has found, for the first time, seven risk genes for insomnia. With this finding the researchers have taken an important step towards the unravelling of the biological mechanisms that cause insomnia. In addition, the finding proves that insomnia is not, as is often claimed, a purely psychological condition. Today, Nature Genetics publishes the results of this research.

Insomnia is probably the most common health complaint. Even after treatment, poor sleep remains a persistent vulnerability for many people. By having determined the risk genes, professors Danielle Posthuma (VU and VUmc) and Eus Van Someren (Netherlands Institute for Neuroscience, VU and VUmc), the lead researchers of this international project, have come closer to unravelling the biological mechanisms that cause the predisposition for insomnia.

Hope and recognition for insomniacs

Professor Van Someren, specialized in sleep and insomnia, believes that the findings are the start of a path towards an understanding of insomnia at the level of communication within and between neurons, and thus towards finding new ways of treatment.

He also hopes that the findings will help with the recognition of insomnia. “As compared to the severity, prevalence and risks of insomnia, only few studies targeted its causes. Insomnia is all too often dismissed as being ‘all in your head’. Our research brings a new perspective. Insomnia is also in the genes.”

In a sample of 113,006 individuals, the researchers found 7 genes for insomnia. These genes play a role in the regulation of transcription, the process where DNA is read in order to make an RNA copy of it, and exocytosis, the release of molecules by cells in order to communicate with their environment. One of the identified genes, MEIS1, has previously been related to two other sleep disorders: Periodic Limb Movements of Sleep (PLMS) and Restless Legs Syndrome (RLS). By collaborating with Konrad Oexle and colleagues from the Institute of Neurogenomics at the Helmholtz Zentrum, München, Germany, the researchers could conclude that the genetic variants in the gene seem to contribute to all three disorders. Strikingly, PLMS and RLS are characterized by restless movement and sensation, respectively, whereas insomnia is characterized mainly by a restless stream of consciousness.

Genetic overlap with other characteristics

The researchers also found a strong genetic overlap with other traits, such as anxiety disorders, depression and neuroticism, and low subjective wellbeing. “This is an interesting finding, because these characteristics tend to go hand in hand with insomnia. We now know that this is partly due to the shared genetic basis,” says neuroscientist Anke Hammerschlag (VU), PhD student and first author of the study.

Different genes for men and women

The researchers also studied whether the same genetic variants were important for men and women. “Part of the genetic variants turned out to be different. This suggests that, for some part, different biological mechanisms may lead to insomnia in men and women,” says professor Posthuma. “We also found a difference between men and women in terms of prevalence: in the sample we studied, including mainly people older than fifty years, 33% of the women reported to suffer from insomnia. For men this was 24%.”

The risk genes could be tracked down in cohorts with the DNA and diagnoses of many thousands of people. The UK Biobank — a large cohort from England that has DNA available — did not have information as such about the diagnosis of insomnia, but they had asked their participants whether they found it difficult to fall asleep or to have an uninterrupted sleep. By making good use of information from slaapregister.nl (the Dutch Sleep Registry), the UK Biobank was able, for the first time, to determine which of them met the insomnia profile. Linking the knowledge from these two cohorts is what made the difference.

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Irregular sleeping patterns linked to poorer academic performance in college students

Previous research has analyzed variations in sleep patterns including number of hours slept, quality of sleep, and sleep-wake times, and found an association with cognitive impairments, health and performance; however, few studies have considered or accurately quantified the effects of regular sleep patterns. In a new study at Brigham and Women’s Hospital, researchers objectively measured sleep and circadian rhythms, and the association to academic performance in college students, finding that irregular patterns of sleep and wakefulness correlated with lower grade point average, delayed sleep/wake timing, and delayed release of the sleep-promoting hormone melatonin. The results are published in Scientific Reports on June 12, 2017.

Researchers studied 61 full-time undergraduates from Harvard College for 30 days using sleep diaries. They quantified sleep regularity using the sleep regularity index (SRI), a newly devised metric. Researchers examined the relationship between the SRI, sleep duration, distribution of sleep across the day, and academic performance during one semester.

“Our results indicate that going to sleep and waking up at approximately the same time is as important as the number of hours one sleeps,” stated Andrew J. K. Phillips, PhD, biophysicist at the Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital and lead author on the paper. “Sleep regularity is a potentially important and modifiable factor independent from sleep duration,” Phillips said.

Students with more regular sleep patterns had better school grades on average. Researchers found no significant difference in average sleep duration between most students with irregular sleep patterns and most regular sleepers.

“We found that the body clock was shifted nearly three hours later in students with irregular schedules as compared to those who slept at more consistent times each night, stated Charles A. Czeisler, PhD, MD, Director of the Sleep Health Institute at Brigham and Women’s Hospital, and senior author on the paper. “For the students whose sleep and wake times were inconsistent, classes and exams that were scheduled for 9 a.m. were therefore occurring at 6am according to their body clock, at a time when performance is impaired. Ironically, they didn’t save any time because in the end they slept just as much as those on a more regular schedule.”

By measuring the timing of melatonin release at sleep onset, the researchers were able to assess the timing of circadian rhythms. On average, melatonin was released 2.6 hours later in students with the most irregular sleep patterns, compared to students with more regular sleep patterns.

“Using a mathematical model of the circadian clock, we were able to demonstrate that the difference in circadian timing between students with the most irregular sleep patterns and students with regular sleep patterns was consistent with their different patterns of daily light exposure,” stated Phillips. “In particular, regular sleepers got significantly higher light levels during the daytime, and significantly lower light levels at night than irregular sleepers who slept more during daytime hours and less during nighttime hours.”

Researchers note that the circadian clock takes time to adjust to schedule changes, and is highly sensitive to patterns of light exposure. Irregular sleepers, who frequently changed the pattern of when they slept and consequently their pattern of light-dark exposure, experienced misalignment between the circadian system and the sleep-wake cycle.

Researchers conclude that light based interventions, including increased exposure to daytime light and less exposure to electronic light-emitting devices before bedtime, may be effective in improving sleep regularity.

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Sequential options prompt future thinking, boost patience

When faced with a tempting choice, it can be hard to stop and think through the potential consequences, but new research suggests that framing the choice as a sequence of events can help us exercise patience by prompting us to imagine the future. The findings are published in Psychological Science, a journal of the Association for Psychological Science.

“People often have difficulty forgoing immediate temptations, like hitting the snooze button on the alarm, for the sake of later benefits. One possible reason is that people tend to consider the immediate consequences of a particular action, like getting a few more minutes of sleep, more than the later ones, like not having time for breakfast,” explains Adrianna Jenkins of the Helen Wills Neuroscience Institute and Haas School of Business at the University of California, Berkeley.

“Past work has shown that a subtle change in how choices are framed can increase people’s patience. We found evidence that this change affects patience by increasing imagination and its role in decision-making,” she adds.

A considerable amount of research has shown that people who are able to forego immediate temptations in lieu of future rewards experience all sorts of benefits later on, including greater physical, psychological, and financial well-being. But the typical explanation for this ability — using willpower to tamp down our immediate desires — does not always seem to underlie increases in patience. For example, research on framing effects indicates that people’s ability to exercise patience can differ based on small differences on how current and future choices are presented, even without changes in willpower.

Jenkins and UC Berkeley colleague Ming Hsu wondered whether reframing decisions might increase people’s reliance on a second possible route to patience: imagination.

In one experiment, Jenkins and Hsu presented 122 participants with a series of binary choices and the participants had to choose which option they preferred. In some cases, the options were framed as independent — for example, they could choose between receiving $15 tomorrow or $20 in 30 days. In other cases, however, the options were framed as sequential — that is, receive $15 tomorrow and $0 in 30 days versus receive $0 tomorrow and $20 in 30 days.

Replicating past research, people were more likely to exercise patience when the options were framed as a sequence relative to when they were framed as independent. Importantly, the options were financially equivalent regardless of how they were framed.

In a second online experiment, 203 participants were randomly assigned to receive either an independently framed choice or a sequentially framed choice with higher stakes: $100 tomorrow or $120 in 30 days. This time, Jenkins and Hsu also measured participants’ imagination.

In the second experiment, people were more likely to imagine the potential outcomes of the options when choices were framed as sequences. This increased reliance on imagination was apparent in both participants’ self-reports and also in the notes they took about what they were thinking while making their decision.

In a third experiment, the researchers looked at brain imaging data from another group of participants making the same kinds of decisions. They found that when options were framed as a sequence, choosing the patient option was linked to activity in brain regions associated with imagination. When the options were framed as independent, choosing the patient option was more strongly linked with activity in brain areas associated with willpower.

These findings, the researchers say, provide evidence that reframing options as a sequence influenced the route by which participants exercised patience.

“Our findings suggest that imagination and willpower represent dissociable routes to patience,” says Jenkins. “Willpower might enable people to override impatient impulses after they’re formed, whereas imagining future consequences might affect the formation of the impulses themselves.”

Imagining future consequences may be a particularly useful strategy, the researchers note, when circumstances are less than ideal — say, when you’re multitasking, distracted, stressed, or just tired — since is it possible for willpower to be compromised in these situations.

So when your alarm clock rings tomorrow and you don’t feel like getting out of bed, try reframing your options. Instead of choosing between “get out of bed now” and “sleep 20 more minutes,” try thinking of your options more in terms of “get out of bed now and have time for breakfast” or “sleep 20 more minutes and have no time for breakfast.” It may just help you throw off the covers and get ahead on your day.

 

Mom and baby sleeping in same room associated with less sleep, unsafe sleep habits

The American Academy of Pediatrics (AAP) recommends parents keep babies in the same room with them to sleep for the first year to prevent sudden infant death syndrome (SIDS). But room sharing between babies and mothers beyond the first four months is associated with less sleep for babies and unsafe sleeping practices the AAP is hoping to prevent, according to Penn State College of Medicine researchers.

While room sharing can be justified for the first six months based on the fact that 90 percent of SIDS cases happen in this timeframe, Dr. Ian Paul, professor of pediatrics, said evidence was lacking for the 6 to 12 month recommendation made by the AAP, which also conflicts with infant sleep expert guidance. This lack of evidence led the researchers to address the question of the effects of parent-baby room sharing on sleep habits and quality for infants 6 to 12 months old.

“Inadequate infant sleep can lead to obesity, poor sleep later in life and can negatively affect parents,” Paul said. “Many pediatricians and sleep experts question the room-sharing recommendation until one year because infants begin to experience separation anxiety in the second half of the first year, making it problematic to change sleep locations at that stage. Waiting too long can have negative effects on sleep quality for both parents and infants in both the short and long term.”

To study the association between room-sharing and sleep outcomes, researchers used data they had already collected from the INSIGHT study, which included 279 mothers who delivered at Penn State Health Milton S. Hershey Medical Center, and their babies. A questionnaire was completed by mothers when their babies were 4 and 9 months old and assessed sleep duration, location, night waking, night feedings, bedtime routines and sleep behaviors. Sleep duration, location and patterns were also assessed at 12 and 30 months. Paul and colleagues report their findings in Pediatrics.

At 4 months, children who already slept independently in their own room averaged 45 minutes longer stretches of continuous sleep than those who shared a room with a parent. At nine months, the gap widened: those who learned to sleep independently by 4 months had sleep stretches that averaged 1 hour and 40 minutes longer than babies who were still sleeping in their parent’s room, 542 minutes vs. 442 minutes respectively. Total sleep over the night was also greater for the babies who were in their own room.

These early decisions by parents had lasting effects. At 30 months, babies who had room shared at 9 months slept, on average, 45 minutes less per night than those who were independent sleepers at 4 and 9 months.

Room sharing also affected sleep safety. Babies who shared a room at 4 months were more likely to have a blanket, pillow or other unapproved object that could increase chances of SIDS in their crib than those who slept in their own room. Additionally, babies who shared a room were more likely to be moved into their parent’s bed overnight at both 4 and 9 months old.

“Perhaps our most troubling finding was that room-sharing was associated with overnight transitions to bed-sharing, which is strongly discouraged by the American Academy of Pediatrics,” Paul said. “Bed-sharing overnight was more common in our sample among 4- and 9-month-olds who began the night on a separate surface in their parents’ room.”

Paul said the study questions the American Academy of Pediatrics’ recommendation to room-share for the entire first year.

“Our findings showing poorer sleep-related outcomes and more unsafe sleep practices for babies who room-share beyond early infancy suggest that the American Academy of Pediatrics should reconsider and revise the recommendation pending evidence to support it.”

Paul said that parents should discuss this study and safe sleep guidance with their pediatrician and noted that breastfeeding outcomes were not different between groups at age 4 months and beyond.

Limitations of this study include the study population being mostly white with a lower number of low-income participants. The recommendations may not translate into lower income homes that may not have a separate bedroom for baby.

Other researchers on the study are Patricia Carper, clinical trial coordinator, Penn State College of Medicine; Emily Hohman, research associate, Jennifer Savage, associate director and Michele Marini, research technologist, Center for Childhood Obesity Research, Penn State; Eric Loken, University of Connecticut, Storrs; Stephanie Anzman-Frasca, University at Buffalo, and Leann Birch, University of Georgia.

National Institutes of Health, Children’s Miracle Network, USDA and Ashley Nicole Shellenberger SIDS Research Fund funded this study. (R01DK088244, R01DK099364, 2011-67001-30117)

 

Sleep regularity is important for the happiness and well-being of college students

Preliminary results from the “SNAPSHOT study,” an NIH-funded collaborative research project between the Division of Sleep and Circadian Disorders at Brigham and Women’s Hospital, and MIT Media Lab Affective Computing Group, suggest that keeping a regular sleep pattern contributes to the happiness and well-being of college students.

Results show that higher sleep regularity was significantly related to higher morning and evening happiness, healthiness and calmness during the week. Transitioning from an irregular weekly sleep pattern to a regular pattern also was associated with improved well-being, both during the week of regular sleep and on the day following it.

“We found that week-long irregular sleep schedules are significantly associated with lower self-reported morning and evening happiness, healthiness, and calmness during the week even after controlling for weekly average sleep duration,” said lead author Akane Sano, PhD, research scientist in the Media Lab Affective Computing Group at the Massachusetts Institute of Technology in Cambridge.

The analysis involved 204 college students between the ages of 18 and 25 years who participated in a 30-day field study. Sleep timing and duration were monitored using actigraphy, along with daily morning and evening Internet-based diaries. Self-reports of well-being (happiness, healthiness, and calmness) were collected using daily diaries.

“Irregular sleep-wake schedules are common in our modern society,” said Sano. “Our results indicate the importance of sleep regularity, in addition to sleep duration, and that regular sleep is associated with improved well-being.”

According to the authors, this study underlines the necessity of considering sleep regularity as an important factor for understanding self-reported well-being.

The research abstract was published recently in an online supplement of the journal Sleep and will be presented Monday, June 5, in Boston at SLEEP 2017, the 31st Annual Meeting of the Associated Professional Sleep Societies LLC (APSS), which is a joint venture of the American Academy of Sleep Medicine and the Sleep Research Society.

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Sleep extension improves response time, reduces fatigue in professional baseball players

Preliminary results from a new study suggest that short-term sleep extension improves response time and daytime functioning of professional baseball players.

Results show that after five nights of sleep extension, professional baseball players from an MLB organization demonstrated a 13-percent improvement on a cognitive processing speed test by reacting 122 milliseconds faster. They also responded 66 milliseconds faster on a test of selective attention when confronted with distractors. According to the authors, a fastball takes approximately 400 milliseconds to travel from the pitcher to the hitter, requiring batters to have optimal visual search strategies to distinguish and react to different types of pitches.

“Our research indicates that short-term sleep extension of one additional hour for five days demonstrated benefits on athletes’ visual search abilities to quickly respond when faced with distractors,” said lead author Cheri D. Mah, MS, research fellow at the University of California San Francisco Human Performance Center.

The research team led by Mah conducted a randomized, controlled trial during a 4-week training camp. Seventeen professional baseball players from an MLB organization completed a two-day baseline of habitual sleep. Athletes then were randomized to either five nights of sleep extension or five nights of habitual sleep. Pre- and post-cognitive tests included the Digit Symbol Substitution Task (DSST) and an adaptive visual search task. Mood and daytime sleepiness were evaluated with the Profile of Mood States (POMS) and Epworth Sleepiness Scale.

In the sleep extension group, the objective, estimated sleep duration measured by actigraphy increased by 0.6 hours per night from 6.3 to 6.9 hours. Assessments of fatigue, tension, and daytime sleepiness all decreased by more than one-third after sleep extension.

“Fatigue over a season can negatively impact performance and possibly pitch recognition,” said Mah. “These findings suggest that short-term sleep loading during periods of high training volumes may be a practical recovery strategy and fatigue countermeasure that has daytime performance benefits.”

The research abstract was published recently in an online supplement of the journal Sleep and will be presented Monday, June 5, in Boston at SLEEP 2017, the 31st Annual Meeting of the Associated Professional Sleep Societies LLC (APSS), which is a joint venture of the American Academy of Sleep Medicine and the Sleep Research Society.

In a previous study published in the journal Sleep, Mah found that a 5-7 week sleep extension period was associated with improvements in specific measures of basketball performance among collegiate athletes.

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Bed partners may unintentionally contribute to the perpetuation of insomnia

Preliminary results from a new study show that partners of people who have insomnia may try to be supportive by engaging in a range of behaviors that unintentionally contradict treatment recommendations.

Results show that 74 percent of partners encouraged an early bedtime or late wake time, which is in direct conflict with the principles of cognitive behavioral therapy for insomnia (CBTI). Forty-two percent also encouraged doing other things in bed, such as reading or watching TV, and 35 percent encouraged naps, caffeine or reduced daytime activities.

“It is possible that partners are unwittingly perpetuating insomnia symptoms in the patient with insomnia,” said lead author Alix Mellor, PhD, postdoctoral research fellow and coordinator of the Researching Effective Sleep Treatments (REST) project in the School of Psychological Sciences at Monash University in Victoria, Australia. “It is therefore important for more data to be collected to determine whether insomnia treatments may better benefit patients and their partners by proactively assessing and addressing bed partner behaviors in treatment programs.”

The research team was led by Mellor and chief investigator Sean P. A. Drummond, PhD, professor of clinical neuroscience at the Monash Institute of Cognitive and Clinical Neurosciences. They studied 31 partners, including 14 women, of individuals seeking treatment for insomnia as part of a randomized, controlled trial investigating partner-assisted interventions for insomnia. Partners completed several questionnaires at baseline: the Family Accommodation Scale, Beck Anxiety Inventory, and Dyadic Adjustment Scale. The insomnia patients also completed baseline questionnaires, including the Insomnia Severity Index, and kept a sleep diary for one week prior to starting treatment.

Results also show that bed partners made accommodations that affected their own functioning, including their sleep and life outside of work. This may explain why partners who attempted to be helpful experienced more anxiety, even though the insomnia patients perceived the relationship to be more satisfying.

“Our preliminary results suggest that while some of these behaviors make the patient feel supported, their partner may be experiencing more anxiety,” said Mellor.

The research abstract was published recently in an online supplement of the journal Sleep and will be presented Sunday, June 4, in Boston at SLEEP 2017, the 31st Annual Meeting of the Associated Professional Sleep Societies LLC (APSS), which is a joint venture of the American Academy of Sleep Medicine and the Sleep Research Society.

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Losing sleep over climate change

Climate change may keep you awake — and not just metaphorically. Nights that are warmer than normal can harm human sleep, researchers show in a new paper, with the poor and elderly most affected. According to their findings, if climate change is not addressed, temperatures in 2050 could cost people in the United States millions of additional nights of insufficient sleep per year. By 2099, the figure could rise by several hundred million more nights of lost sleep annually.

The study was led by Nick Obradovich, who conducted much of the research as a doctoral student in political science at the University of California San Diego. He was inspired to investigate the question by the heat wave that hit San Diego in October of 2015. Obradovich was having trouble sleeping. He tossed and he turned, the window AC in his North Park home providing little relief from the record-breaking temperatures. At school, he noticed that fellow students were also looking grumpy and bedraggled, and it got him thinking: Had anyone looked at what climate change might do to sleep?

Published by Science Advances, the research represents the largest real-world study to date to find a relationship between reports of insufficient sleep and unusually warm nighttime temperatures. It is the first to apply the discovered relationship to projected climate change.

“Sleep has been well-established by other researchers as a critical component of human health. Too little sleep can make a person more susceptible to disease and chronic illness, and it can harm psychological well-being and cognitive functioning,” Obradovich said. “What our study shows is not only that ambient temperature can play a role in disrupting sleep but also that climate change might make the situation worse by driving up rates of sleep loss.”

Obradovich is now a postdoctoral fellow at Harvard’s Kennedy School of Government and a research scientist at the MIT Media Lab. He is also a fellow of the Center for Marine Biodiversity and Conservation at UC San Diego’s Scripps Institution of Oceanography. Obradovich worked on the study with Robyn Migliorini, a student in the San Diego State University/UC San Diego Joint Doctoral Program in Clinical Psychology, and sleep researcher Sara Mednick of UC Riverside. Obradovich’s dissertation advisor, social scientist James Fowler of UC San Diego, is also a co-author.

The study starts with data from 765,000 U.S. residents between 2002 and 2011 who responded to a public health survey, the Behavioral Risk Factor Surveillance Survey from the Centers for Disease Control and Prevention. The study then links data on self-reported nights of insufficient sleep to daily temperature data from the National Centers for Environmental Information. Finally, it combines the effects of unusually warm temperatures on sleep with climate model projections.

The main finding is that anomalous increases in nighttime temperature by 1 degree Celsius translate to three nights of insufficient sleep per 100 individuals per month. To put that in perspective: If we had a single month of nightly temperatures averaging 1 degree Celsius higher than normal, that is equivalent to 9 million more nights of insufficient sleep in a month across the population of the United States today, or 110 million extra nights of insufficient sleep annually.

The negative effect of warmer nights is most acute in summer, the research shows. It is almost three times as high in summer as during any other season.

The effect is also not spread evenly across all demographic groups. Those whose income is below $50,000 and those who are aged 65 and older are affected most severely. For older people, the effect is twice that of younger adults. And for the lower-income group, it is three times worse than for people who are better off financially.

Using climate projections for 2050 and 2099 by NASA Earth Exchange, the study paints a bleak picture of the future if the relationship between warmer nights and disrupted sleep persists. Warmer temperatures could cause six additional nights of insufficient sleep per 100 individuals by 2050 and approximately 14 extra nights per 100 by 2099.

“The U.S. is relatively temperate and, in global terms, quite prosperous,” Obradovich said. “We don’t have sleep data from around the world, but assuming the pattern is similar, one can imagine that in places that are warmer or poorer or both, what we’d find could be even worse.”

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Sacrificing sleep for love

Sleep is important, but if there is something more important or interesting to do — for example, taking care of a baby, finishing a grant proposal before a deadline, or reading a fascinating book — we may stay up late. Sleep in fruit flies is a lot like human sleep, and like humans, flies can keep themselves awake if there is something important to do. In research published on May 16th in eLife, researchers report discovery of neurons that allow male fruit flies to suppress sleep so they can court female flies.

“The idea that sleep and courtship might compete with each other is intuitive but had not been studied experimentally, and the underlying neural mechanisms had not been explored. We wanted to know how the sleep drive and sex drive compete to determine behavior,” says Kyunghee Koh, PhD, Associate Professor of Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University and senior author on the study.

The researchers found that whereas a male fly normally spends much of the night awake and courting if there is a female nearby, a male that has recently mated several females (and therefore has low sex drive) ignores the female and goes to sleep. They discovered that a small number of neurons (termed MS1 for male specific 1) release octopamine, a neurotransmitter similar to human noradrenalin, to keep male flies awake in a sexual setting. Silencing MS1 neurons allows males to go to sleep even when there is a female around, while artificially activating MS1 neurons keeps males awake even when they are alone. Interestingly, although females have the same neurons, their activation has no effect on female sleep. MS1 neurons do not belong to a previously identified group of neurons important for male sexual behavior, but instead communicate with them to keep males awake so they can court.

It is unclear whether similar mechanisms are at work in humans, but Dr. Koh says “it is known that noradrenalin promotes wakefulness in humans. Our work suggests noradrenalin may be especially important for suppressing sleep when we have to engage in other urgent activities.” However, the first goals for her team are to identify specific neurons that communicate directly with MS1 neurons and examine how their activation leads to sleep suppression and how MS1 neuronal activity is regulated.

This work was supported by NIH grants R21NS094782 and R01NS086887 and predoctoral fellowships from the Portuguese Foundation for Science and Technology.

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Surprise communication found between brain regions involved in infant motor control

A newborn’s brain is abuzz with activity.

Day and night, it’s processing signals from all over the body, from recognizing the wriggles of the child’s own fingers and toes to the sound of mommy’s or daddy’s voice.

Though much of how the infant brain works and develops remains a mystery, University of Iowa researchers say they have uncovered a new mode of communication between two relatively distant regions. And, it turns out that sleep is key to this communication.

When two areas of the brain communicate, their rhythms will often synchronize. One well-known brain rhythm, the theta rhythm, is most closely associated with the hippocampus, a region in the forebrain important for consolidating memories and navigation, among other functions. In experiments with infant rats, the researchers showed for the first time that the hippocampus oscillates in lockstep with the red nucleus, a brain-stem structure that plays a major role in motor control. Importantly, the hippocampus and red nucleus synchronize almost exclusively during REM (active) sleep.

Rats and humans both spend much of their early lives in REM sleep. In human newborns, eight hours of every day is occupied by REM sleep alone. And because rat brains and human brains have the same basic structure, UI researchers believe the same communication, between the same regions, is likely occurring in human infants. They also suspect disruptions to that linkage may contribute to the motor-control problems that often accompany disorders such as autism and schizophrenia.

“Our findings provide a possible route to understanding the early emergence of motor problems in human infants. Because we found that communication between the hippocampus and red nucleus occurred primarily during REM sleep, disrupting normal sleep in early infancy could interfere with the strengthening of the communication links among forebrain and brainstem structures,” says Mark Blumberg, a professor in the UI Department of Psychological and Brain Sciences and corresponding author on the study, published in the journal Current Biology.

“We feel this work opens new doors to a host of important questions that have been largely overlooked,” Blumberg says.

Carlos Del Rio-Bermudez, a Fulbright Scholar who joined Blumberg’s lab for his doctoral studies, says he was surprised by the findings.

“Although a lot is known about the theta rhythm in the hippocampus and other forebrain structures, no one seems to have suspected that it might also be involved in communication between the hippocampus and a brain-stem structure like the red nucleus,” Del Rio-Bermudez says.

According to Blumberg, this discovery supports the idea that REM sleep is important for early brain development and that brain rhythms play a significant role in this process.

The researchers point out that an infant’s red nucleus and other similar structures contribute heavily to motor control at a time in development when other brain structures, including the motor cortex, are still developing.

Considering the many similarities in the brain and behavior of infant rats and humans, “it would be extraordinary if similar events are not also happening in us,” Blumberg says.

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Alternative treatment approach for neonatal abstinence syndrome may shorten hospital stay

New research suggests a revamped, “common sense” approach to treating newborns suffering opioid withdrawal — gauging whether the baby can eat, sleep and be consoled within 10 minutes before administering drugs to wean them off exposure — may safely reduce the length of hospitalization they need.

An abstract of the study, “A Novel Approach to Evaluating and Treating Infants with Neonatal Abstinence Syndrome (NAS),” will be presented at the Pediatric Academic Societies 2017 Meeting in San Francisco on Sunday, May 7.

An estimated 95 percent of U.S. hospitals use the Finnegan Neonatal Abstinence Scoring System (FNASS) to guide treatment, based on 21 symptoms of opioid withdrawal. These include tremors, seizures, excessive crying, diarrhea, vomiting, congestion, sneezing and other symptoms that can make it difficult for the baby to eat and sleep. Babies with severe symptoms are started on pharmacologic therapy, typically using the narcotics morphine or methadone.

Researchers at Yale-New Haven Children’s Hospital examined whether more non-pharmacologic interventions for NAS in a modified approach called the Eat, Sleep, Console (ESC) model, such as providing a low-stimulation environment, having mothers room-in with their infants and feeding them frequently, could help infants go home sooner.

Fifty babies were included in the study between March 2014 and August 2015. The researchers determined traditional FNASS guidelines would have indicated starting morphine treatment in 30 (60 percent) of the infants. With the ESC guidelines used instead, however, morphine was started on just 6 patients (12 percent).

The study also found that of the 301 patient days evaluated, the FNASS score recommended starting or increasing morphine therapy on one-quarter of the days. Instead, following the ESC model, morphine was started or increased on just 3 percent of the days.

Using the alternative approach helped reduce the length of hospitalization for infants with NAS from 22.5 to 5.9 days without an increase in readmission rate, said Matthew Grossman, MD, an assistant professor of pediatrics at Yale School of Medicine and Quality and Safety Officer for the hospital who launched the ESC model there in 2011.

Abstract author Matthew Lipshaw, MD, FAAP, said the findings are particularly important with the current opioid epidemic in the United States. The incidence of NAS increased fivefold between 2000-2015 in the United States, Dr. Lipshaw noted, resulting in an estimated $1.5 billion in hospital charges in 2012 alone.

“We found that a common sense approach based on the functional well-being of infants is a safe and more effective way to treat NAS than traditional treatment guidelines, substantially reducing exposure to opioids in these infants and better meeting patient needs,” Dr. Lipshaw said.

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Musical beds: Co-sleeping is more common than some parents admit

Parents know that co-sleeping is considered a no-no, but many still allow their children to crawl into bed with them at night.

Doctors generally discourage co-sleeping, because of its link to sudden infant death syndrome or SIDS. However, Susan Stewart, a professor of sociology at Iowa State University, found that many parents still co-sleep with their children, and it is a phenomenon that extends well beyond the infant and toddler years.

In her new book, “Co‑Sleeping: Parents, Children, and Musical Beds,” Stewart explores the reasons why parents allow their children to sleep with them instead of in their own beds. She found a lot of activity takes place at night in a variety of scenarios. In some families, children started out in their own bed and then went into their parents’ bed in the middle of the night. This sometimes resulted in one parent being “squished out,” forcing them to move to the couch or the child’s bed.

In other households, children might be allowed to sleep on a mattress or in a sleeping bag on the floor of their parents’ bedroom. Stewart says the prohibition against co-sleeping is so strong that in one family the mother, wanting to be close to her child, slept on a mattress next to the child’s crib.

One of the reasons Stewart wanted to study this issue is because most research on co-sleeping comes from the medical field and is related to SIDS. Stewart is one of the first researchers to take a broader approach and include parents who slept with infants as well as children up to age 13. In the book, she defines co-sleeping as: “One or both parents sometimes or regularly sleeping with their children in the same bed or room at night or part of the night.”

Stewart interviewed 51 parents who co-sleep and found many would prefer not to sleep with their children. The shame and stigma associated with co-sleeping is so great that about half of the parents denied or avoided discussing it with family or their pediatrician. However, some of parents said they slept better and had fewer disruptions throughout the night when everyone slept in one room or bed, rather than spending the night playing musical beds.

“Parents are exhausted, they’re stressed and honestly, it’s often easier to co-sleep,” Stewart said. “There’s no one size fits all, and in my view, there is no right or wrong.”

While co-sleeping is frowned upon in the U.S., it is perfectly normal in other cultures. Stewart says it’s more acceptable in Scandinavian, Asian and South American countries, where rates of SIDS are far lower than in the U.S. The decision to co-sleep is sometimes related to economics, because there are not enough rooms or beds in the home.

Impact on relationships

Stewart asked both mothers and fathers how co-sleeping affected their relationships and intimacy. Most parents said co-sleeping did interfere at times with physical intimacy, but it was not a major issue. As for emotional intimacy, Stewart found co-sleeping allowed busy parents to spend quality time as a family. This was especially true for dads who tended to spend more time away from home.

“Parents are putting their children ahead of their own relationship, at least in the short-term,” she said. “There is a downside to that, but most of the parents viewed it as temporary.”

Stewart says if parents co-sleep safely, there are many positive benefits. For example, studies have found that children who sleep with their parents feel more secure or attached to their parents, and as a result are more independent. However, co-sleeping can negatively affect sleep quality. Many parents mentioned waking up numerous times at night as a result of their children kicking them or flailing about.

In general, Americans are getting poor quality sleep. In the book, Stewart includes data from the National Sleep Foundation that states:

  • 64 percent of Americans reported a sleep problem at least a few nights a week
  • 10 percent of parents rated their children’s sleep as “fair” or “poor”
  • Poor sleep is associated with anxiety, reduced work productivity, aggression, obesity, poor school performance, lower marital happiness and increased mortality
  • Adopting good sleep habits is one of the most effective ways to preserve one’s physical and psychological health

How does it start? How does it end?

Parents had a hard time recalling exactly when and how they started co-sleeping. Many said it wasn’t planned or discussed, it “just happened.” Stewart says one father shared that they had bought a crib, but they never even took it out of the box.

Putting an end to co-sleeping often starts with a plan, but executing it can be a challenge. Stewart says parents gave several examples of setting timeframes, such as telling their children they would have to sleep in their own bed once school starts. Despite efforts by parents to put an end to co-sleeping, for many families it ended naturally without a plan.

During her conversations with parents, Stewart learned a lot about the pressure parents feel to raise a “perfect” child. Many parents used work-related words or phrases — parenting is 24-7, being on the clock, all hands on deck — to describe the incredible amount of activity that takes place at night. Stewart says in American society there is a great deal of competition among parents, which is why many families hide the fact that they co-sleep.

“There is a lot of pressure. Everybody thinks they know how to parent better than everybody else,” Stewart said. “Unfortunately, there’s a lot of judgment and, in general, very little support for parents.”

Stewart says these comments and concerns from parents speak to larger issues in the U.S., such as the need for paid maternity leave and adequate vacation or sick leave that benefit families.

 

Early school starts pit teens in a conflict between society, biology

The idea of sleep is supposed to evoke feelings of peace, relaxation and refreshment, but when expert Mary Carskadon talks about teen sleep in school districts with early start times, she uses far less comfortable words.

“Social policy clashes with what we see from the biology,” said Carskadon, a professor of psychiatry and human behavior at the Warren Alpert Medical School of Brown University. “For teens, when they have not gotten enough sleep and they have to get up too early, they are crushed in the morning.”

Over decades of study, Carskadon has shown that two systems that regulate sleep, circadian rhythms and sleep pressure, both change as children grow up. While they still need the same amount of sleep throughout childhood — ideally 9 to 10 hours — older kids naturally become inclined to go to sleep later (as their circadian rhythms skew later). That means they become biologically predisposed to sleep later, too, to fully relieve that sleep pressure — or biological need to sleep. Yet society frequently requires that they wake early.

“They are incredibly sleepy from the sleep pressure, but also they have to be at school at a time when their circadian system wants them to be asleep,” she said.

Carskadon will share the insights from her research as one of many speakers at “Adolescent Sleep, Health, and School Start Times,” a national conference in Washington, D.C., from April 27 to 28. Co-organized by Dr. Judy Owens, director of sleep medicine at Boston Children’s Hospital and former professor at Brown University, the event will feature scientists, physicians and K-12 educators from across the country who will gather to discuss the health, educational and controversial policy implications of the issue.

The issue is a hot button in several states, including Rhode Island where a newly proposed law would set a statewide high school start time of 8:30 a.m. Carskadon, meanwhile, has been invited to address the Rhode Island Association of School Committees in May even as she gears up for a new study this summer.

The biology of bedtime

Carskadon’s work began in the 1970s when she was a graduate student at Stanford University. She surveyed teens about their sleep habits and preferences. Perhaps not surprisingly, the results showed that teens stayed up later and slept less than when they were younger. The prevailing assumption was that they needed less sleep. But when she experimentally put teens on a schedule that allowed them to sleep longer, they did. Teens didn’t need less sleep than younger kids, she concluded. The fact that they also stopped waking on their own was apparent in the data, but was not Carskadon’s focus at the time.

“We kind of missed that clue until we started looking at it in different ways,” she said.

In a nationwide round of surveys in the early 1990s, she asked sixth graders when they felt best during the day and what their sleep preferences were. She also asked them to rate their maturity. She found an interesting trend.

“The more mature they rated themselves, the more evening type they rated themselves,” she said. “There was a hint that maybe something was going on around the time of pubertal development that has to do with the circadian system.”

In her Bradley Hospital sleep lab located on the campus of Butler Hospital in Rhode Island, Carskadon began to expand her research to incorporate biomarkers such as saliva levels of melatonin, a natural hormone driven by circadian rhythms that cues the onset of sleepiness. She found that given the same light/dark schedule, teens will produce melatonin at later times than younger kids, indicating their circadian rhythm grows fundamentally later as they age.

One of her most seminal findings came in the late 1990s, when she studied 10th graders who had a high school start time of about 7:20 a.m. Wrist-worn sleep monitors showed they were getting about 7 hours of sleep a night. When she brought them into the lab, she’d wake them up for their regular school start time but then let them go back to sleep starting at 8:30 — a time when in school they’d be expected to be well underway with taking exams or listening intently to lectures.

“About half of them looked like they had a major sleep disorder — narcolepsy,” she said. “At 8:30, half of the kids fell asleep in under a minute and went directly into REM sleep which means that their brains were set up

in a very strong way to be asleep. When you are trying to teach and learn, it’s a non-starter.”

As her lab grew and she added expertise to the team, she also began to look at brain wave patterns of teens as they slept. That helped her observe the buildup of sleep pressure. Her lab’s finding was that sleep pressure builds up more slowly in older kids. It’s easier for them to stay awake longer. But what doesn’t change is how quickly they relieve sleep pressure: they need just as much sleep.

Her studies have continued all along. In 2014, she added more to the evidence of a later shift in sleep schedules with age, not by comparing groups of differently aged kids as before, but by comparing kids to themselves as they aged. Carskadon and colleagues published a study in PLOS ONE tracking the same children for more than two years. The data clearly showed that as they got older, they went to bed later.

A recurring theme in Carskadon’s studies is that later-to-bed and later-to-rise is not entirely a behavioral choice — it’s a physiological imperative.

“The force behind the change that we see behaviorally is in the biology,” she said.

Even the newest threat to teen sleep — the temptations of portable screens lit up with games and social media — has direct and specific biological impact on sleep. In a 2015 study she found that the sleep biology of boys and girls aged 9 to 15 who were in the earlier stages of puberty was especially sensitive to light at night compared to older teens, meaning that late-night gadget use is particularly disruptive for young teens.

The clash with policy

For all the scientific evidence she has found, Carskadon acknowledges that policy is driven by many factors. Her studies have identified significant overall trends, but individuals vary widely, she said, and there are no doubt many households where teens are managing early school days just fine.

Meanwhile, there are a lot of reasons why school districts start when they do, she said. For some families, for example, having older kids home from school before younger kids allows parents to be sure that younger kids have an older sibling to come home to.

“The school system is central to community life,” she acknowledged.

But the biological evidence for letting teens sleep in longer is overwhelming, she said. So long as school starts at a time when they physiologically still need to be asleep, she said, teenagers on average may be consigned to suffer from a “social jetlag” in which the timing of life is not the timing of the body.

 

Gene mutation helps explain night owl behavior

Some people stay up late and have trouble getting up in the morning because their internal clock is genetically programmed to run slowly, according to a study published April 6 in Cell. A mutation in a gene called CRY1 alters the human circadian clock, which dictates rhythmic behavior such as sleep/wake cycles. Carriers of the gene variant experienced nighttime sleep delays of 2-2.5 hours compared to non-carriers.

“Carriers of the mutation have longer days than the planet gives them, so they are essentially playing catch-up for their entire lives,” says first author Alina Patke, a research associate in the lab of principal investigator Michael Young, Richard and Jeanne Fisher Professor and Head of the Laboratory of Genetics at The Rockefeller University.

Night owls are often diagnosed at sleep clinics with delayed sleep phase disorder (DSPD). This study is the first to implicate a gene mutation in the development of DSPD, which affects up to 10% of the public, according to clinical studies.

People with DSPD often struggle to fall asleep at night, and sometimes sleep comes so late that it fractures into a series of long naps. DSPD and other sleep disorders are associated with anxiety, depression, cardiovascular disease, and diabetes. People with DSPD also have trouble conforming to societal expectations and morning work schedules.

“It’s as if these people have perpetual jet lag, moving eastward every day,” says Young. “In the morning, they’re not ready for the next day to arrive.”

Patke is a night owl and usually works late into the night. She, however, does not carry the CRY1 variant. Not all cases of DSPD are attributable to this gene mutation. However, Young and Patke found it in 1 in 75 of individuals of non-Finnish, European ancestry in a gene database search. “Our variant has an effect on a large fraction of the population,” she says.

Young, who has studied the genes involved in the circadian clock of the fruit fly, connected with clinical researchers at the Weill Cornell Medical College to understand the molecular underpinnings of human sleep disorders. By studying the skin cells of people with DSPD, he and Patke discovered a mutation in CRY1, which helps drive the circadian clock.

The circadian clock is a fundamental element of life on Earth and has remained more or less the same, genetically, throughout the evolution of animals. “It’s basically the same clock from flies to humans,” Young says.

Normally the clock begins its cycle by building up proteins, call activators, in a cell. These activators produce their own inhibitors that, over time, cause the activators to lose their potency. When all the activators in the cell have been silenced, inhibitors are no longer produced and eventually degrade. Once they’ve all gone, the potency of the activators surges, and the cycle begins again.

The CRY1 protein is one of the clock’s inhibitors. The mutation Young and Patke found is a single-point mutation in the CRY1 gene, meaning just one letter in its genetic instructions is incorrect. Yet this change causes a chunk of the gene’s resulting protein to be missing. That alteration causes the inhibitor to be overly active, prolonging the time that the activators are suppressed and stretching the daily cycle by half an hour or more.

In addition to their initial study of a multigenerational family in the U.S., Young and Patke collaborated with clinical researchers at Bilkent University to analyze the sleep patterns of six families of Turkish individuals, 39 carriers of the CRY1 variant and 31 non-carriers. The carriers had delayed sleep onset times and some had fractured, irregular sleep patterns. The mid-point of sleep for non-carriers was about 4 a. m. But for carriers, the mid-point was shifted to 6-8 a.m.

Because the mutation does not disable the protein, it can have an effect on individuals whether they carry one or two copies of the gene. Of the 39 Turkish carriers studied, 8 had inherited the mutation from both parents, and 31 had inherited only one copy of the mutation.

The circadian clock responds to external environmental cues, so it is possible for people to manage the effects of the mutation on sleep. For instance, one carrier in the study reported maintaining a sleep routine through self-enforced regular sleep and wake times and exposure to bright light during the day. “An external cycle and good sleep hygiene can help force a slow-running clock to accommodate a 24-hour day,” says Patke. “We just have to work harder at it.”

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Deep sleep may act as fountain of youth in old age

As we grow old, our nights are frequently plagued by bouts of wakefulness, bathroom trips and other nuisances as we lose our ability to generate the deep, restorative slumber we enjoyed in youth.

But does that mean older people just need less sleep?

Not according to UC Berkeley researchers, who argue in an article published April 5 in the journal Neuron that the unmet sleep needs of the elderly elevate their risk of memory loss and a wide range of mental and physical disorders.

“Nearly every disease killing us in later life has a causal link to lack of sleep,” said the article’s senior author, Matthew Walker, a UC Berkeley professor of psychology and neuroscience. “We’ve done a good job of extending life span, but a poor job of extending our health span. We now see sleep, and improving sleep, as a new pathway for helping remedy that.”

Unlike more cosmetic markers of aging, such as wrinkles and gray hair, sleep deterioration has been linked to such conditions as Alzheimer’s disease, heart disease, obesity, diabetes and stroke, he said.

Though older people are less likely than younger cohorts to notice and/or report mental fogginess and other symptoms of sleep deprivation, numerous brain studies reveal how poor sleep leaves them cognitively worse off.

Moreover, the shift from deep, consolidated sleep in youth to fitful, dissatisfying sleep can start as early as one’s 30s, paving the way for sleep-related cognitive and physical ailments in middle age.

And, while the pharmaceutical industry is raking in billions by catering to insomniacs, Walker warns that the pills designed to help us doze off are a poor substitute for the natural sleep cycles that the brain needs in order to function well.

“Don’t be fooled into thinking sedation is real sleep. It’s not,” he said.

For their review of sleep research, Walker and fellow researchers Bryce Mander and Joseph Winer cite studies, including some of their own, that show the aging brain has trouble generating the kind of slow brain waves that promote deep curative sleep, as well as the neurochemicals that help us switch stably from sleep to wakefulness.

“The parts of the brain deteriorating earliest are the same regions that give us deep sleep,” said article lead author Mander, a postdoctoral researcher in Walker’s Sleep and Neuroimaging Laboratory at UC Berkeley.

Aging typically brings on a decline in deep non-rapid eye movement (NREM) or “slow wave sleep,” and the characteristic brain waves associated with it, including both slow waves and faster bursts of brain waves known as “sleep spindles.”

Youthful, healthy slow waves and spindles help transfer memories and information from the hippocampus, which provides the brain’s short-term storage, to the prefrontal cortex, which consolidates the information, acting as the brain’s long-term storage.

“Sadly, both these types of sleep brain waves diminish markedly as we grow old, and we are now discovering that this sleep decline is related to memory decline in later life,” said Winer, a doctoral student in Walker’s lab.

Another deficiency in later life is the inability to regulate neurochemicals that stabilize our sleep and help us transition from sleep to waking states. These neurochemicals include galanin, which promotes sleep, and orexin, which promotes wakefulness. A disruption to the sleep-wake rhythm commonly leaves older adults fatigued during the day but frustratingly restless at night, Mander said.

Of course, not everyone is vulnerable to sleep changes in later life: “Just as some people age more successfully than others, some people sleep better than others as they get older, and that’s another line of research we’ll be exploring,” Mander said.

Meanwhile, non-pharmaceutical interventions are being explored to boost the quality of sleep, such as electrical stimulation to amplify brain waves during sleep and acoustic tones that act like a metronome to slow brain rhythms.

However, promoting alternatives to prescription and over-the-counter sleep aids is sure to be challenging.

“The American College of Physicians has acknowledged that sleeping pills should not be the first-line kneejerk response to sleep problems,” Walker said. “Sleeping pills sedate the brain, rather than help it sleep naturally. We must find better treatments for restoring healthy sleep in older adults, and that is now one of our dedicated research missions.”

Also important to consider in changing the culture of sleep is the question of quantity versus quality.

“Previously, the conversation has focused on how many hours you need to sleep,” Mander said. “However, you can sleep for a sufficient number of hours, but not obtain the right quality of sleep. We also need to appreciate the importance of sleep quality.

“Indeed, we need both quantity and quality,” Walker said.