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Neuroscience, Research, Sleep, Stanford News

Stumbling upon circadian rhythms

Stumbling upon circadian rhythms

PrintIn my job as a science writer, I get to hear lots of amazing stories of discovery. In some cases, researchers have worked diligently to solve one question for decades. Others I talk to describe exciting Eureka! moments where their data suddenly made sense. But some of my favorite stories are those where a scientist is studying one thing, only to make an off-the-cuff observation that leads them in a totally new direction.

In researching circadian rhythms for the latest issue of Stanford Medicine magazine, I heard lots of this last kind of story. There are many obvious ways that circadian rhythms influence biology: our sleep cycles, the way our stomachs start to grumble for lunch at the same time every day, and how many plants close their flowers each night. But scientists are also starting to reveal lots of hidden, unexpected ways that circadian rhythms – the natural cycles in living organisms – affect us. Over just the past few years, researchers in disparate fields have made chance observations that have made them think twice about the timing of their experiments; daily circadian cycles in our bodies can affect everything from how we metabolize drugs to how our immune system acts, they’ve found.

Craig Heller, PhD, who co-directs the Stanford Down Syndrome Research Center, told me about how he was testing a new drug to improve memory in mice with Down syndrome. During the course of his experiments, he noticed that mice who received the drug at night didn’t respond the same way as mice that received a dose in the morning. It led him to start investigating the link between learning, memory, and daily sleep cycles. What he discovered doesn’t just have implications for Down syndrome, but for learning and memory more broadly.

Then, sleep researcher Emmanuel Mignot, MD, PhD, of the Stanford Center for Narcolepsy, walked me through the story of how he and other scientists discovered a link between the immune system and narcolepsy. It all started, he explained, after an odd epidemiological observation: narcolepsy was more often diagnosed in the spring than in the fall.

Of course, lots of what we know about how circadian clocks tick along inside our bodies, keeping time with the world around us, comes from tireless, carefully planned out benchwork, and that can’t be discredited. But some of the most surprising new links I describe in my feature come from scientists taking leaps across fields to explain something they found curious. Check out my feature, “Hacking the Biological Clock,” to learn more about what Heller, Mignot, and other scientists have found on these journeys of discovery.

Sarah C.P. Williams is a freelance science writer based in Hawaii.

Previously: Stanford Medicine magazine reports on time’s intersection with health, Study shows altered circadian rhythms in the brains of depressed people and Narcolepsy = autoimmune disease
Illustration by Harry Campbell

Chronic Disease, Health Policy, In the News, Pediatrics, Public Health, Sleep

Talking about teens’ “great sleep recession”

Talking about teens' "great sleep recession"

Sleepy Teen Student

We all understand, at some level, that sleep is critical to our health. But there’s a cultural undercurrent that belies that understanding: We tend to glorify the go-getters who can survive on four or five hours of sleep, lauding their productivity and drive. Numerous studies have shown that Americans of all ages – kids, teens, and adults – are not getting enough sleep.

More and more, researchers are warning that lack of sleep can damage our long-term health. Just yesterday, Rafael Pelayo, MD, with the Stanford Center for Sleep Sciences and Medicine, was on KQED’s Forum radio program to discuss a new study looking at some alarming trends in teen sleep habits. The study, titled “The Great Sleep Recession” was published this week in the scientific journal Pediatrics. It showed that over the past 20 years, teens have been getting less sleep. Girls, minority teens, teens in urban areas and of low socioeconomic status were less likely to get at least seven hours of sleep than male, white teens. What’s more, minority teens and low SES teens were likely to report they thought they got enough sleep.

During the show, Pelayo spoke about our relationship with sleep and the challenges of sticking to a “sleep budget”:

When I read the title [of the study] it made me think of Bill Dement, who talks – at Stanford – about a sleep debt and not having enough total sleep. And a sleep debt has been growing and accumulating in people who have used sleep as something as optional in their lives. These students are… modeling after their parents, who are not getting enough sleep… But in the kids, it’s a particularly hard problem for them, they feel pressure to not get enough sleep.

Pelayo went on to say that parents and teens tend to prioritize other things, like homework, over sleep – but what they should be doing is setting aside a certain amount of time for sleep. “If the homework doesn’t get done, it doesn’t get done. They can’t make homework more important than sleep,” he said.

That last statement is a pretty radical suggestion, but if we are to avoid the fall-out from our bad sleep habits, radical changes may be the only solution.

Previously: With school bells ringing, parents should ensure their children are doing enough sleeping, Stanford docs discuss all things sleep, Study shows poor sleep habits as a teenager can “stack the deck against you for obesity later in life” and What are the consequences of sleep deprivation?
Photo by Alberto Vacarro

Sleep, Stanford News

Narcoleptic Chihuahua joins Stanford sleep researcher’s family

Narcoleptic Chihuahua joins Stanford sleep researcher's family

Watson the dog

Meet Watson, the narcoleptic chihuahua. He’s just like any other pampered pup, except he collapses when he’s excited, thanks to his narcolepsy. I enjoyed a demonstration of Watson’s special skills last week, when I visited Stanford sleep researcher Emmanuel Mignot, MD, PhD.

Mignot discovered the gene that triggers narcolepsy in dogs more than a decade ago, and before getting Watson he had recently lost his narcoleptic companion, Bear, a black Belgian schipperke who would swoon over broccoli. (For a lovely elegy to Bear, check out this KQED piece, including video.)

Still heartbroken, Mignot wasn’t in the market for a new dog. And certainly not for a chihuahua.

But a phone call from a breeder who had an unadoptable, sleepy dog, led to a visit to Vermont – and before long, Watson arrived. Now, Mignot is smitten, cooing to the squirmy dog in his native French. I detailed the story in the current issue of Inside Stanford Medicine.

Mignot uses Watson to demonstrate the effects of an cataplectic attack to children who are suffering from the disease. (Watson’s entertaining performance can calm frightened patients, Mignot told me.) In my piece I outlined what happened when Watson was offered a chunk of pork (one of his triggers) last week: “Watson took a big sniff and staggered backwards, struggling to ward off the attack that was paralyzing his muscles — pushing him toward sleep in just seconds. He recovered slightly, climbing to his feet and lunging for the food.”

Watson is particularly susceptible to grass-fed filet mignon, Whole Foods roast beef and new toys. He also collapses for joy when Mignot returns home from work, Mignot told me.

Interestingly, the causes of narcolepsy in humans and dogs may differ:

In humans, narcolepsy is caused when the immune system attacks certain neurons in the brain. These neurons produce a peptide called hypocretin that helps promote wakefulness and inhibits dreaming. Some dogs have that type of narcolepsy as well, although others have a genetic form that stems from a mutation in the hypocretin peptide receptor gene. Watson is a family pet and has not undergone any kind of genetic testing, so Mignot doesn’t know what type of narcolepsy he has.

Previously: Narcolepsy=autoimmune disease, Stanford center launches Huffington Post blog on the “very mysterious process” of sleep and Studying pediatric sleep disorders an “integral part” of the future of sleep medicine 
Photo by Becky Bach

Behavioral Science, Public Health, Sleep

Six simple ways to improve your sleep for the holidays

Six simple ways to improve your sleep for the holidays

IMG_5595The holiday season is usually one of the busiest – and often most stressful – times of the year. It’s also a season that often brings poor sleep. To improve your health and your mood, consider six simple ways that you can maintain healthy sleep during the hustle and bustle of the holidays and even discover the resolve to improve your sleep in 2015.

1. Go to bed when you’re sleepy.

It seems obvious, but it isn’t always easy to do: Sleep most easily comes when we are feeling sleepy. Insomnia, characterized by difficulty falling or staying asleep, can plague us throughout the year. With the added stress of the holidays, it can be even harder to fall asleep.

Many insomniacs will start to go to bed earlier, or stay in bed long after waking, to make up for lost sleep. This desperation often thins out sleep and makes it less refreshing. Imagine showing up for a holiday feast after having snacked all day. You wouldn’t have much of an appetite. If you spend too much time in bed, or take naps, you similarly will show up for the eight-hour feast of sleep without much interest.

Prolonged wakefulness helps to build our drive for sleep and staying up a little later until you feel sleepy can ease insomnia.Preserving 30 to 60 minutes to relax before bed can also aid this transition.

2. Ease yourself into a new time zone to prevent jet lag.

If you’re flying across the world, or even across the country, you may find that your sleep suffers. This is due to our body’s natural circadian rhythm, which regulates the timing or our desire for sleep. This rhythm is based in genetics, but it is strongly influenced by environmental cues, especially morning sunlight exposure.

If you suddenly change your experience of the timing of light and darkness by hopping on a jet plane, your body will have to play catch up. As a general rule: “West is best and east is a beast.” This points out that westward travel is more tolerated because it’s nearly always easier to stay up later than it is to wake up earlier.

Another rule of thumb is that it takes one day to adjust for each time zone changed. If you travel across three time zones, from San Francisco to New York City, it will take about three days to adjust to the new time zone. This adaptation can be expedited by adopting the new time zone’s bedtime and wake time before you depart. If you’re like most people, your best intentions might not lead to pre-trip changes.

Never fear: To catch up once you arrive, delay your bedtime until you are sleepy, fix your wake time with an alarm, and get 15 minutes of morning sunlight upon awakening.

3. Put an end to the snoring.

Whether you’re staying in grandma’s spare room or sharing a hotel suite, close quarters during the holidays may call attention to previously unnoted snoring and other sleep-disordered breathing like sleep apnea.

Remember that children should never chronically snore; if they do, they should be seen by a sleep specialist. Adults don’t have to snore either. Snoring is commonly caused by the vibration of the soft tissues of the throat. If the airway completely collapses in sleep, this is called sleep apnea. This may lead to fragmented sleep with nocturnal awakenings and daytime sleepiness. It is also commonly associated with teeth grinding and getting up to urinate at night.

When sleep apnea is moderate to severe, it may increase the risk of other health problems including hypertension, diabetes, heart attack, stroke, and dementia. It’s more than a nuisance, and if you or a loved one experience it, further evaluation and treatment is warranted.

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Research, Sleep

Holiday nightcap? Drinking before bed may be counterproductive

Holiday nightcap? Drinking before bed may be counterproductive

nightcap2

If you’ve ever taken a drink of alcohol before bed to help you fall asleep, you’re not alone – approximately 20 percent of Americans do so regularly. But new research from the University of Missouri shows that while a nightcap can make you sleepy in the short term, regular alcohol consumption before bed interferes with the body’s sleep regulator and can actually cause insomnia.

A study published last month in Alcohol helps us understand alcohol’s effects in a new way. It was previously thought that alcohol shifts the circadian rhythm, the body’s “internal clock,” resulting in simply being sleepy sooner; in fact, it disrupts the mechanism by which the brain “feels” tired. Alcohol increases the production of adenosine, a naturally occurring chemical that accumulates outside cells when you’ve been awake for a long time; it signals the need for sleep by blocking “wakefulness” receptors in the basal forebrain. Adenosine levels decrease during sleep, maintaining the brain’s sleep/wake homeostasis.

Alcohol-induced adenosine wears off too quickly, which makes for less restful sleep in the short term, and can compromise the brain’s ability to maintain homeostasis in the long term (i.e., insomnia).

I asked Stanford sleep expert Brandon Peters, MD, to weigh in and he told me:

I concur that alcohol should not be used as a sleep aid. Though alcohol may induce sleepiness, as it quickly wears off it fragments sleep, leading to awakenings. Alcohol also can relax the muscles of the upper airway and contribute to obstructive sleep apnea and snoring. It is recommended that alcohol not be consumed for the several hours preceding bedtime.

What to do instead? Peters suggests:

Rather than relying on an alcohol-containing nightcap, insomnia can be improved with changes as part of a structured cognitive-behavioral therapy for insomnia (CBTI) program. Sleeping pills are also not a preferred option; you don’t need medication to feel hungry, so why would you need medication to feel sleepy? Sleep is a natural process that can be enhanced with simple interventions. If difficulty falling or staying asleep persists beyond 3 months, assistance should be sought from a board-certified sleep specialist.

Photo by Stephen Janofsky

Fertility, Men's Health, Research, Sleep

Sleep apnea linked with male infertility

Sleep apnea linked with male infertility

14258396551_0d3b8edb81_zOver the past two decades, there have been a number of studies suggesting that men’s sperm counts have been steadily declining. Now research out of Spain and published in the journal Sleep suggests a connection between sleep apnea and decreased sperm production.

Michael Eisenberg, MD, a Stanford expert in male fertility, thinks the results are important but inconclusive. When reached for comment he told me:

My research focuses on the links between a man’s overall health and his reproductive health, so this study has a lot of connections. I think it shows another health factor that can impact fertility; we are seeing sleep apnea more and more commonly, and here’s something showing a link with decreased sperm production. A big drawback of the study is that before we can incorporate it in clinical practice the research needs to be replicated in humans.

The research, conducted collaboratively by research institutions in Spain, induced intermittent hypoxia (lack of oxygen) in male mice to mimic sleep apnea. These mice, along with a control group who had been experiencing normal oxygen levels, were mated, and researchers compared the numbers of pregnant females and fetuses, which were significantly lower for the hypoxic group.

Previously: Male infertility can be warning of hypertension, Stanford study finds, Poor semen quality linked to heightened mortality rate in men and Low sperm count can mean increased cancer risk
Photo by Kelsey

Neuroscience, Research, Sleep, Stanford News, Technology

Cheating jet lag: Stanford researchers develop method to treat sleep disturbances

Cheating jet lag: Stanford researchers develop method to treat sleep disturbances

jets landing in sunset - 560

Last month, I went to a conference back East. It was a short trip, four days, and I was jet lagged the whole time. I spent my mornings gulping down hot coffee to help shake off the sleepy haze; in the evenings, when I should have been making up the lost sleep, I was wired, tossing and turning in bed. I could have tried adjusting to East Coast time in the days before I left by getting to bed a few hours earlier and getting up around 4 AM, but that would have required a level of coordination and planning that I’m unlikely to muster in the days before an out-of-town trip.

So I was curious when I learned that a team of Stanford researchers, led by neurobiologist Jamie Zeitzer, PhD, were working on a technique that helps people shift their sleep cycles by flashing light briefly at their eyes while they sleep. They recently published their findings in the Journal of Biological Rhythms.

Beyond the obvious job of vision, our eyes and brain are constantly processing information about the light around us. Light affects our moods and the daily ebb and flow of our biological clocks. It influences when we are sleepiest and most alert. Our brains do a lot of this work behind the scenes and because it happens unconsciously, we are rarely aware of these circadian rhythms – unless something disturbs them, like flying across several time zones.

Zeitzer and his team recruited volunteers and had them get on a routine sleep-wake cycle, going to bed and waking up at the same time every day for about two weeks. The researchers then had the volunteers come sleep in the lab, where the experimental group was given a series brief flashes of light about two millisconds long – about as long as a camera flash – aimed at their eyes. A control group slept in complete darkness, and the volunteers didn’t know which group they were assigned to. The team then measured whether the subjects’ sleep cycle had been affected by measuring the amount of melatonin in their blood. The brain floods the body with melatonin a couple of hours before bedtime and continues releasing the hormone until about an hour after wake time.

The researchers found that the volunteers who got the light flashes were able to shift the sleep phase of their circadian systems. What was surprising was that the intervention did not noticeably disturb the subjects’ sleep. The volunteers in the experimental group didn’t report any less restful sleep than the controls. “This kind of treatment can help people adjust even before they leave for a trip,” says Zeitzer. “Leaving for Australia, the night before you leave, you can adjust a couple of hours. On the plane, you can adjust a couple more. By the time you arrive, you’re already half-way adjusted.”

Besides jet-lagged travelers, this technique could also help teenagers who have a hard time getting up at the right time (a clinical condition for many that goes beyond adolescent laziness) and shift workers. Current treatments for sleep disturbances include sitting in front of bright lights for sometimes hours at a time, which often means it’s only used in extreme cases.

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Health and Fitness, In the News, Research, Sleep, Stanford News

Superathletes sleep more, says Stanford researcher

Superathletes sleep more, says Stanford researcher

alarm-clock-146469_640Hit snooze again – it just might boost your performance, Stanford sleep expert Cheri Mah believed. Seems intuitive, yet research findings were needed.

Mah originally tapped Stanford’s men’s basketball team to test her theory. When the team went from an average of 6.5 to 8.5 hours of sleep a night, they hit 11 percent more free throws and sprinted more quickly. Her work grabbed headlines at the time, and now it’s featured in Mark McClusky’s  forthcoming book, Faster, Higher, Stronger: How Sports Science is Creating a New Generation of Superathletes — and What We Can Learn from Them.

The Atlantic excerpted a key section from the book today; here’s McClusky (who also edits Wired.com):

For us humans, sleep is completely crucial to proper functioning. As we’ve all experienced, we’re simply not as adept at anything in our lives if we don’t sleep well…

It seems like certain kinds of athletic tasks are more affected by sleep deprivation. Although one-off efforts and high-intensity exercise see an impact, sustained efforts and aerobic work seem to suffer an even larger setback. Gross motor skills are relatively unaffected, while athletes in events requiring fast reaction times have a particularly hard time when they get less sleep.

McClusky goes on to write that Mah’s research “strongly suggests that most athletes would perform much better with more sleep – if they could get it.” But it’s tricky for top athletes to get enough sleep. Fly across the country, or the world, and your sleep schedule is skewered. And West Coast teams have it particularly hard:

In 2013, the Seattle Mariners flew more than 52,000 miles while the Chicago White Sox, with their central location and nearby division rivals, only flew about 23,000… Bouncing around the country, leaving late, arriving early, having to play the next day—it’s no surprise that travel and the management of sleep is a huge problem for athletes.

Some athletes squeeze in an afternoon nap to boost their rest times, McClusky said. And that sounds like a mighty fine idea to me.

Previously: Ask Stanford Med: Cheri Mah responds to questions on sleep and athletic performance, Expert argues that for athletes, “sleep could mean the difference between winning and losing,” Why your sleeping habits may be preventing you from sticking to a fitness routine and A slam dunk for sleep: Study shows benefits of slumber on athletic performance
Image by OpenClips

Neuroscience, Research, Sleep

Memory of everyday events may be compromised by sleep apnea

Memory of everyday events may be compromised by sleep apnea

sleeping_11.3.14Previous imaging studies have shown that sleep apnea, which causes periods of disrupted breathing during the night, is associated with tissue loss in regions of the brain that process memory. Now new research published in the Journal of Neuroscience offers more evidence that the sleep disorder can cause difficulty in remembering where you left your keys and other daily events.

In a small study (subscription required), people with severe sleep apnea spent two separate nights at the NYU Sleep Disorders Center. At the lab, individuals were administered a baseline examination consisting of playing a video game requiring them to navigate three-dimensional spatial mazes. During one night of the experiment, participants’ use of their continuous positive airway pressure (CPAP) machine was reduced during REM sleep allowing sleep apnea to naturally occur. On the second night, they resumed normal use of the CPAP. Individuals played the video game before and after each sleep period.

As Medical News Today reports:

When sleep was aided by therapeutic CPAP all night, researchers observed a 30 percent overnight improvement in maze completion time from their baseline examinations. However, when REM sleep was disrupted by sleep apnea, there was not only no improvement from baseline testing, but, in fact, subjects took 4 percent longer to complete the maze tests.

Equally important, when sleep apnea occurred in REM sleep, subjects did not experience delayed reaction times on a separate test to measure attention, called a psychomotor vigilance test. [Lead researcher Andrew Varga, MD, PhD,] says that this suggests that sleepiness or lack of attention were not reasons for the decline in spatial memory, as indicated by the maze performance after experiencing sleep apnea in REM sleep.

Sleep apnea affects approximately 18 million adults in the United States. While the disorder is difficult to diagnose in children because of monitoring techniques, it’s estimated that a minimum of 2 to 3 percent of kids suffer from sleep apnea and some believe it could be as high as 10 to 20 percent, according to data from the National Sleep Foundation.

Previously: “Sleep drunkenness” more prevalent than previously thought, Study shows women with gestational diabetes at increased risk for obstructive sleep apnea, Why untreated sleep apnea may cause more harm to your health than feeling fatigued and How effective are surgical options for sleep apnea?
Photo by Jared Polin

Neuroscience, Research, Sleep, Videos

How sleep acts as a cleaning system for the brain

How sleep acts as a cleaning system for the brain

Here’s one more reason why getting a good night’s sleep is critical to your health. As neuroscientist Jeff Iliff, PhD, explains in this just released TEDMED video, the brain has a specialized waste-disposal system that’s only active when we’re slumbering. Watch the talk above to learn how this system clears the brain of toxic metabolic byproducts that could lead to Alzheimer’s disease and other neurological disorders.

Previously: Why sleeping in on the weekends may not be beneficial to your health, The high price of interrupted sleep on your health and Examining how sleep quality and duration affect cognitive function as we age

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