Searching For Shut Eye: Study Identifies Possible Sleep Gene

While scientists and physicians know what happens if you don’t get six to eight hours of shut-eye a night, investigators have long been puzzled about what controls the actual need for sleep. Researchers at the University of Pennsylvania School of Medicine might have an answer, at least in fruit flies. In a recent study of fruit flies, they identified a gene that controls sleep.
“We spend -- or should spend -- a third of our lives sleeping,” says Amita Sehgal, PhD, Professor of Neuroscience and an Investigator with the Howard Hughes Medical Institute (HHMI). “The idea that so much time is spent in sleep is intriguing. Also, sleep deprivation has serious health consequences and impairs cognitive function.”
This study was published in the latest Science.
Fruit flies typically sleep 12 hours a day. Sehgal and her team studied 3,500 fruit flies and found mutants that survived on little to no sleep – one to two hours a day or none at all. The sleepless flies had a mutation of a gene that Sehgal and her team have named Sleepless. They believe the Sleepless gene encodes a protein that affects whether potassium ion channels in the brain stay open or closed. When the channels are open, the brain is connected and working – the fly is awake. When closed, the channel shuts down and the fly sleeps. The insomniac fruit flies had less of the Sleepless-produced protein.
The lack of sleep didn’t come without consequences. The Sleepless fruit flies lived about half as long as fruit flies that did not carry the mutation. They also experience impaired coordination and restlessness in their few hours of sleep.
Sleep is regulated by two processes: circadian and homeostatic. Circadian regulation affects the timing of sleep, and the homeostatic mechanism affects the need for sleep. The Sleepless gene affects the homeostatic mechanism.
Sleep isn’t just for humans – it’s been observed in everything from flies to dogs to people, indicating that it’s essential to life. Insufficient and poor-quality sleep is an increasing problem in industrialized nations. In the U.S. alone, about 70 million people suffer from chronic sleep problems, which reduce workplace productivity, affect quality of life and can even be lethal.
“In the long term, we hope that human equivalents of our gene will be isolated and will not only further our understanding of human sleep, but perhaps also serve as drug targets to promote sleep or treat insomnia,” says Sehgal.

The societal, economic burden of insomnia is high

The largest proportions of all insomnia-related expenses are attributed to lost job productivity, absences from work and alcohol used as a sleep aid.
A study in the Jan. 1 issue of the journal Sleep indicates that the indirect costs of untreated insomnia are significantly greater than the direct costs associated with its treatment. The study estimates that the total annual cost of insomnia in the province of Quebec is 6.5 billion Canadian dollars, representing about one percent of the province's $228.5 billion in gross domestic product for 2002.
Annual indirect costs of insomnia related to lost hours of productivity are estimated to be $5 billion, representing the largest proportion (76 percent) of all insomnia costs. The annual estimate of insomnia-related lost productivity is 27.6 days per year for individuals with insomnia syndrome, and 6.2 days per year for people with insomnia symptoms. The second-highest cost of insomnia is attributed to job absenteeism, with $970.6 million – 14.7 percent of the total economic burden of insomnia - estimated to be lost annually due to insomnia-related absences. Individuals with insomnia syndrome are absent from work an estimated 4.36 days per year because of insomnia.
Lead author of the study, Meagan Daley, PhD, professor of psychology and business, in Quebec City, Canada stated that costs associated with the use of alcohol as a sleep aid exceed those associated with consultations and the use of medications and over-the-counter products.
The total estimated annual cost of alcohol used for promoting sleep is $339.8 million, which is the highest direct cost, representing 60 percent of all direct costs and five percent of all insomnia-related costs. The annual cost of insomnia-related consultations with a health-care professional is estimated to be $85.3 million (32.6 percent of all direct costs and 2.9 percent of overall costs), and an estimated $16.5 million is spent annually on prescription medications for insomnia (only 2.8 percent of direct costs and less than one percent of overall costs). According to the authors the centralization of the health-care system in Quebec keeps salaries and capital costs relatively low, and most medications prescribed for sleep in Canada are inexpensive generic drugs.
Daley said, "This study demonstrated that it is not the costs associated with seeking out treatment (for insomnia), such as consulting health-care professionals or purchasing medications or over-the-counter products that constitute anywhere near the largest proportion of expenditures. Rather, indirect costs constitute the greatest proportion of all insomnia costs, with about ¾ of overall costs being due to lost work productivity."
This study was a part of a larger epidemiological study documenting the natural history of insomnia. A total of 948 randomly selected adults were chosen from the province of Quebec, Canada, to participate. The mean age of participants was 43.7 years. Sixty percent of participants were female. Volunteers completed questionnaires on sleep, health, use of health-care services and products, accidents, work absences and reduced productivity in the previous three months. Data were also obtained from the government-administered health-insurance board in Quebec regarding consultations and hospitalizations.

Comparing Sleep And Awake Schedules

The newer blue-enriched lights used in light boxes are no more effective at advancing circadian rhythms than the standard white lights that have been in use for decades according to a study by researchers in the Rush University Medical Center Biological Rhythms Research Lab. The study results will be published in the journal Sleep Medicine Vol. 10, issue 3 (April 2009).
These results are important for people who use therapeutic light boxes and scheduled exposure to light and darkness to rest their natural body clocks, such as shift workers and those who have certain sleep issues like delayed sleep phase disorder (DSPD), a condition in which an individual has a biological predisposition to go to bed and awaken on a much later schedule than most people.
Previous research has shown that the human circadian clock is most sensitive to short-wavelength (blue) light, but more research is needed regarding the dosage, timing and wavelength of light treatment.
Researchers at Rush were interested in finding out if bright blue lamps would provide a larger phase advance, or help patients awaken earlier, than the standard bright white lamps commonly used for phase shifting. The study found the blue lamps were no more effective than the standard bright therapy.
“This is good news for people using light treatment because it indicates that the standard white lights that are commercially available work as well as the newer blue-enriched lights. It means that patients are already likely getting a maximal therapeutic response, so there’s no need to rush out and buy a new light box,” said lead author Mark Smith, post-doctoral fellow in the Biological Rhythms Research Laboratory at Rush University Medical Center.
In the study, twenty-two healthy young adults received either a bright white or bright blue-enriched two-hour phase advancing light pulse upon awakening on each of four treatment days. On the first treatment day, the light pulse began eight hours after the dim light melatonin onset, on average about two hours before baseline wake time. On each subsequent day, light treatment began one hour earlier than the previous day, and the sleep schedule was also advanced.
Following the four treatment days, a final phase assessment was conducted. Phase advances of the blue-enriched and white groups were not significantly different.
The effectiveness of the blue-enriched lights at a different light level—less bright—for treatment of different clinical applications, was not tested in this study. According to study authors, blue-enriched lights may be useful for other clinical conditions.

A Night’s Sleep Gives Emotional Memories

For the first time, researchers have found that following a night’s sleep, emotional components of scenes are remembered at the expense of neutral components. In contrast, memories of both emotional and neutral components decayed equally following 12 hours of wakefulness. Sleep also promoted memory for generality over detail, says NIMH grantee Robert Stickgold, Ph.D., of Harvard University, who co-authored the recent study of memory consolidation.
Yet sleep enhanced memory of emotionally-charged objects at a cost. Things in the background of emotional scenes were forgotten more than in scenes containing neutral objects – what the researchers call the “emotional memory trade-off.”
“During sleep, individual components of a scene seem to become unbound,” explained Stickgold. “This allows us to selectively preserve only what’s most important and worth remembering. Physiological and chemical changes in the brain during sleep appear to actively give emotional memories their staying power.”
The new study is the first to demonstrate the emotional memory trade-off over time, and to show how individual components of emotional scene memories evolve differently across time spent asleep and awake. Of a few studies to date that have addressed these issues, none have detected benefit from sleep for neutral memories, say the researchers.
Harvard’s Jessica Payne, Ph.D., Boston College’s Elizabeth Kensinger, Ph.D., Stickgold, and colleagues, report on their findings in the August, 2008 issue of the journal Psychological Science.
Problems with sleep and emotional memories figure prominently in mood and anxiety disorders, and the consequences of inadequate sleep loom for the third of Americans whose sleep-deprived lifestyles interfere with work and social functioning at least a few days each month. The new study is the latest in a series by the Harvard group on how sleep helps consolidate memory.
Based on hints from previous studies, the researchers set out to determine exactly which aspects of memories of emotional events are influenced by sleep. They presented a total of 88 participants with mixed-and-matched sets of pictures of neutral or negatively arousing objects superimposed on neutral or negative backgrounds.
Separate memory tests 12 hours later showed that memory for both objects and backgrounds deteriorated equally, regardless of emotional content, in subjects who studied the pictures in the morning, stayed awake all day, and were tested the same evening. But the disparity in recognition for negative emotional objects vs. their backgrounds more than doubled for participants who were trained in the evening, slept overnight, and were tested the following morning. This increase was entirely due to maintenance of emotional-object memory during sleep, say the researchers. Both after 30 minutes and at 12 hours, memory of negative objects’ backgrounds suffered relative to that for neutral objects.
“There is a popular belief that the consequence of sleep deprivation is simply tiredness, and that a good night’s sleep on the weekend can completely reverse any deleterious effects of mid-week deprivation,” notes Stickgold.
“The many college students, medical, public safety, and transportation personnel who practice such ‘sleep bulimia’ depend on continued learning for the effective performance of their tasks. A clear understanding of exactly how sleep loss contributes to a failure of memory consolidation should provide important arguments to help counter this cultural drift towards less and less sleep,” Stickgold adds.

Have Insomnia? Try Aerobic Exercise

Older adults who have insomnia may sleep better if they eliminate the sleeping pills and take up aerobic exercise such as walking or bicycling, according to a new study. Researchers from Northwestern University are the first to evaluate the impact of aerobic exercise on middle-aged and older adults who suffer with insomnia.

Insomnia in America

About 30 to 40 percent of adults have symptoms of insomnia, which is an inability to fall asleep or stay asleep, and waking up not feeling refreshed. Up to 15 percent of adults have chronic insomnia, which is defined as experiencing these symptoms for a month or longer. Insomnia is more prevalent among women than men, and about half of all middle-aged and older adults suffer with this sleep disorder.
Medications called hypnotics are the most common treatment for insomnia, but they are associated with side effects such as memory problems, morning sedation, headaches, and sleepwalking. Relaxation techniques such as yoga, meditation, and exercise, as well as behavioral therapies have all been found to be helpful in varying degrees, depending on the cause of insomnia and consistently an individual uses them.
New Insomnia and Exercise Study
The study included 23 sedentary adults age 55 and older, mostly women, who had symptoms of chronic insomnia. One group was assigned to aerobic exercise for two 20-minutes sessions four times weekly or one 30-to-40 minute session four times weekly, both for 16 weeks. The participants chose at least two activities such as walking, using a stationary bike, or treadmill.
The control group engaged in a recreational or educational activity, such as a lecture or cooking class, which met for 45 minutes three to five times a week for 16 weeks. Subjects in both groups were given information about good sleep habits.
People in the exercise group reported better quality sleep, fewer symptoms of depression, more energy, and less sleepiness during the day. These improvements raised their status from a poor sleeper to good sleeper.
“This is relevant to a huge portion of the population,” according to Phyllis Zee, MD, director of the Sleep Disorders Center at Northwestern Medicine and senior author of the study. “Exercise is good for metabolism, weight management and cardiovascular health and now it’s good for sleep.”
Sleep quality has a critical impact on both physical and mental health. Because insomnia increases as people age, this population is at greater risk of health problems, which are also already more common in older adults. Therefore, “It is essential that we identify behavioral ways to improve sleep,” says Zee. “Now we have promising results showing aerobic exercise is a simple strategy to help people sleep better.”