SHY hypothesis explains that sleep is the price we pay for learning

MADISON — Why do animals ranging from fruit flies to humans all need to sleep? After all, sleep disconnects them from their environment, puts them at risk and keeps them from seeking food or mates for large parts of the day. Two leading sleep scientists from the University of Wisconsin School of Medicine and Public Health say that their synaptic homeostasis hypothesis of sleep or "SHY" challenges the theory that sleep strengthens brain connections. The SHY hypothesis, which takes into account years of evidence from human and animal studies, says that sleep is important because it weakens the connections among brain cells to save energy, avoid cellular stress, and maintain the ability of neurons to respond selectively to stimuli. "Sleep is the price the brain must pay for learning and memory," says Dr. Giulio Tononi, of the UW Center for Sleep and Consciousness. "During wake, learning strengthens the synaptic connections throughout the brain, increasing the need for energy and saturating the brain with new information. Sleep allows the brain to reset, helping integrate, newly learned material with consolidated memories, so the brain can begin anew the next day. " Tononi and his co-author Dr. Chiara Cirelli, both professors of psychiatry, explain their hypothesis in a review article in today's issue of the journal Neuron. Their laboratory studies sleep and consciousness in animals ranging from fruit flies to humans; SHY takes into account evidence from molecular, electrophysiological and behavioral studies, as well as from computer simulations. "Synaptic homeostasis" refers to the brain's ability to maintain a balance in the strength of connections within its nerve cells. Why would the brain need to reset? Suppose someone spent the waking hours learning a new skill, such as riding a bike. The circuits involved in learning would be greatly strengthened, but the next day the brain will need to pay attention to learning a new task. Thus, those bike-riding circuits would need to be damped down so they don't interfere with the new day's learning. "Sleep helps the brain renormalize synaptic strength based on a comprehensive sampling of its overall knowledge of the environment," Tononi says, "rather than being biased by the particular inputs of a particular waking day." The reason we don't also forget how to ride a bike after a night's sleep is because those active circuits are damped down less than those that weren't actively involved in learning. Indeed, there is evidence that sleep enhances important features of memory, including acquisition, consolidation, gist extraction, integration and "smart forgetting," which allows the brain to rid itself of the inevitable accumulation of unimportant details. However, one common belief is that sleep helps memory by further strengthening the neural circuits during learning while awake. But Tononi and Cirelli believe that consolidation and integration of memories, as well as the restoration of the ability to learn, all come from the ability of sleep to decrease synaptic strength and enhance signal-to-noise ratios. While the review finds testable evidence for the SHY hypothesis, it also points to open issues. One question is whether the brain could achieve synaptic homeostasis during wake, by having only some circuits engaged, and the rest off-line and thus resetting themselves. Other areas for future research include the specific function of REM sleep (when most dreaming occurs) and the possibly crucial role of sleep during development, a time of intense learning and massive remodeling of brain Counselor CEUs

Bradley Hospital researchers link lack of sleep in teens to higher risk of illness

Study also finds consistent sleep pattern can reduce risk of illness EAST PROVIDENCE, R.I. – Newly released findings from Bradley Hospital published in the Journal of Sleep Research have found that acute illnesses, such as colds, flu, and gastroenteritis were more common among healthy adolescents who got less sleep at night. Additionally, the regularity of teens' sleep schedules was found to impact their health. The study, titled "Sleep patterns are associated with common illness in adolescents," was led by Kathryn Orzech, Ph.D. of the Bradley Hospital Sleep Research Laboratory CEUs For Nurses Orzech and her team compared three outcomes between longer and shorter sleepers: number of illness bouts, illness duration, and school absences related to illness. The team found that bouts of illness declined with longer sleep for both male and female high school students. Longer sleep was also generally protective against school absences that students attributed to illness. There were gender differences as well, with males reporting fewer illness bouts than females, even with similar sleep durations. Orzech's team analyzed total sleep time in teens for six-day windows both before and after a reported illness and found a trend in the data toward shorter sleep before illness vs. wellness. Due to the difficulty of finding teens whose illnesses were spaced in such a way to be statistically analyzed, Orzech also conducted qualitative analysis, examining individual interview data for two short-sleeping males who reported very different illness profiles. This analysis suggested that more irregular sleep timing across weeknights and weekends (very little sleep during the week and "catching up" on sleep during the weekend), and a preference for scheduling work and social time later in the evening hours can both contribute to differences in illness outcomes, conclusions that are also supported in the broader adolescent sleep literature. "Some news reaches the general public about the long-term consequences of sleep deprivation, such as the links between less sleep and weight gain," said Orzech. "However, most of the studies of sleep and health have been done under laboratory conditions that cannot replicate the complexities of life in the real world. Our study looked at rigorously collected sleep and illness data among adolescents who were living their normal lives and going to school across a school term." "We showed that there are short-term outcomes, like more acute illness among shorter-sleeping adolescents, that don't require waiting months, years or decades to show up," Orzech continued. "Yes, poor sleep is linked to increased cardiovascular disease, to high cholesterol, to obesity, to depression, etc., but for a teenager, staying healthy for the dance next week, or the game on Thursday, may be more important. This message from this study is clear: Sleep more, and more regularly, get sick less." Mary Carskadon, Ph.D., director of the Bradley Hospital Sleep Research Laboratory, commented on Orzech's study, "We have long been examining the sleep cycles of teenagers and how we might be able to help adolescents - especially high school students - be better rested and more functional in a period of their lives where sleep seems to be a luxury." Carskadon continued, "In the future, these findings identifying specific issues in individual sleep patterns may be a useful way to help adolescents begin to prioritize sleep." ### Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under award numbers MH45945 and MH79179, and T32 training grant MH19927. Direct financial and infrastructure support for this project was received through the Lifespan Office of Research Administration. The principal affiliation of Carskadon is Bradley Hospital (a member hospital of the Lifespan health system in Rhode Island). She is also a professor of psychiatry and human behavior at The Warren Alpert Medical School of Brown University. Orzech was a postdoctoral fellow in the Bradley Hospital Sleep Research Laboratory at the time of the research, and is currently a postdoctoral fellow with the Charting the Digital Lifespan project based at the University of Dundee in Scotland, UK. About Bradley Hospital Founded in 1931, Bradley Hospital, located in East Providence, R.I., was the nation's first psychiatric hospital devoted exclusively for children and adolescents. It remains a nationally recognized center for children's mental health care, training and research. Bradley Hospital was awarded the distinction of 'Top Performer on Key Quality Measures' for both 2011 and 2012 by The Joint Commission, the leading accreditor of health organizations in the U.S. Bradley Hospital is the only hospital in Rhode Island and the only psychiatric hospital in New England to receive this designation. Bradley Hospital is a member of the Lifespan health system and is a teaching hospital for The Warren Alpert Medical School of Brown University. Follow us on Facebook and on Twitter (@BradleyHospital).

Out of sync with the world: Body clocks of depressed people are altered at cell level

Finding of disrupted brain gene orchestration gives first direct evidence of circadian rhythm changes in depressed brains, opens door to better treatment ANN ARBOR, Mich. — Every cell in our bodies runs on a 24-hour clock, tuned to the night-day, light-dark cycles that have ruled us since the dawn of humanity. The brain acts as timekeeper, keeping the cellular clock in sync with the outside world so that it can govern our appetites, sleep, moods and much more. But new research shows that the clock may be broken in the brains of people with depression -- even at the level of the gene activity inside their brain cells. It's the first direct evidence of altered circadian rhythms in the brain of people with depression, and shows that they operate out of sync with the usual ingrained daily cycle. The findings, in the Proceedings of the National Academy of Sciences, come from scientists from the University of Michigan Medical School and other institutions. The discovery was made by sifting through massive amounts of data gleaned from donated brains of depressed and non-depressed people. With further research, the findings could lead to more precise diagnosis and treatment for a condition that affects more than 350 million people worldwide. What's more, the research also reveals a previously unknown daily rhythm to the activity of many genes across many areas of the brain – expanding the sense of how crucial our master clock is professional counselor continuing education In a normal brain, the pattern of gene activity at a given time of the day is so distinctive that the authors could use it to accurately estimate the hour of death of the brain donor, suggesting that studying this "stopped clock" could conceivably be useful in forensics. By contrast, in severely depressed patients, the circadian clock was so disrupted that a patient's "day" pattern of gene activity could look like a "night" pattern -- and vice versa. The work was funded in large part by the Pritzker Neuropsychiatric Disorders Research Fund, and involved researchers from the University of Michigan, University of California's Irvine and Davis campuses, Weill Cornell Medical College, the Hudson Alpha Institute for Biotechnology, and Stanford University. The team uses material from donated brains obtained shortly after death, along with extensive clinical information about the individual. Numerous regions of each brain are dissected by hand or even with lasers that can capture more specialized cell types, then analyzed to measure gene activity. The resulting flood of information is picked apart with advanced data-mining tools. Lead author Jun Li, Ph.D., an assistant professor in the U-M Department of Human Genetics, describes how this approach allowed the team to accurately back-predict the hour of the day when each non-depressed individual died – literally plotting them out on a 24-hour clock by noting which genes were active at the time they died. They looked at 12,000 gene transcripts isolated from six regions of 55 brains from people who did not have depression. This provided a detailed understanding of how gene activity varied throughout the day in the brain regions studied. But when the team tried to do the same in the brains of 34 depressed individuals, the gene activity was off by hours. The cells looked as if it were an entirely different time of day. "There really was a moment of discovery," says Li, who led the analysis of the massive amount of data generated by the rest of the team and is a research assistant professor in U-M's Department of Computational Medicine at Bioinformatics. "It was when we realized that many of the genes that show 24-hour cycles in the normal individuals were well-known circadian rhythm genes – and when we saw that the people with depression were not synchronized to the usual solar day in terms of this gene activity. It's as if they were living in a different time zone than the one they died in." Huda Akil, Ph.D., the co-director of the U-M Molecular & Behavioral Neuroscience Institute and co-director of the U-M site of the Pritzker Neuropsychiatric Disorders Research Consortium, notes that the findings go beyond previous research on circadian rhythms, using animals or human skin cells, which were more easily accessible than human brain tissues. "Hundreds of new genes that are very sensitive to circadian rhythms emerged from this research -- not just the primary clock genes that have been studied in animals or cell cultures, but other genes whose activity rises and falls throughout the day," she says. "We were truly able to watch the daily rhythm play out in a symphony of biological activity, by studying where the clock had stopped at the time of death. And then, in depressed people, we could see how this was disrupted." Now, she adds, scientists must use this information to help find new ways to predict depression, fine-tune treatment for each depressed patient, and even find new medications or other types of treatment to develop and test. One possibility, she notes, could be to identify biomarkers for depression – telltale molecules that can be detected in blood, skin or hair. And, the challenge of determining why the circadian clock is altered in depression still remains. "We can only glimpse the possibility that the disruption seen in depression may have more than one cause. We need to learn more about whether something in the nature of the clock itself is affected, because if you could fix the clock you might be able to help people get better," Akil notes. The team continues to mine their data for new findings, and to probe additional brains as they are donated and dissected. The high quality of the brains, and the data gathered about how their donors lived and died, is essential to the project, Akil says. Even the pH level of the tissue, which can be affected by the dying process and the time between death and freezing tissue for research, can affect the results. The team also will have access to blood and hair samples from new donors. ### The researchers note that the Pritzker funding in combination with federal research funding made it possible for the scientists to study this issue in an exploratory way. The research was historically funded by a Conte Center grant from the National Institute of Mental Health, and partly funded by the William Lion Penzner Foundation, the Della Martin Foundation, the Office of Naval Research (N00014-09-1-059 and N00014-12-1-0366), the National Alliance for Research on Schizophrenia and Depression's Abramson Family Foundation Investigator Award, and an International Mental Health Research Organization – Johnson & Johnson Rising Star Translational Research Award. In addition to Li and Akil, the study's authors are Blynn G. Bunney, Fan Meng, Megan H. Hagenauer, David M. Walsh, Marquis P. Vawter, Simon J. Evans, Prabakhara V. Choudary, Preston Cartagena, Jack D. Barchas, Alan F. Schatzberg, the late Edward G. Jones, Richard M. Myers, U-M MBNI co-director Stanley J. Watson, Jr., and William E. Bunney. Reference: PNAS Early Edition, http://www.pnas.org/cgi/doi/10.1073/pnas.1305814110

Psychologists chase down sleep demons

What do Moby Dick, the Salem witch trials and alien abductions all have in common? They all circle back to sleep paralysis.

Less than 8 percent of the general population experiences sleep paralysis, but it is more frequent in two groups -- students and psychiatric patients -- according to a new study by psychologists at Penn State and the University of Pennsylvania.

Sleep paralysis is defined as "a discrete period of time during which voluntary muscle movement is inhibited, yet ocular and respiratory movements are intact," the researchers state in the current issue of Sleep Medicine Reviews. Hallucinations may also be present in these transitions to or from sleep.

Alien abductions and incubi and succubi, as well as other demons that attack while people are asleep, are implicated as different cultural interpretations of sleep paralysis. The Salem witch trials are now thought possibly to involve the townspeople experiencing sleep paralysis. And in the 19th-century novel Moby Dick, the main character Ishmael experiences an episode of sleep paralysis in the form of a malevolent presence in the room.

Brian A. Sharpless, clinical assistant professor of psychology and assistant director of the psychological clinic at Penn State, noted that some people who experience these episodes may regularly try to avoid going to sleep because of the unpleasant sensations they experience. But other people enjoy the sensations they feel during sleep paralysis.

"I realized that there were no real sleep paralysis prevalence rates available that were based on large and diverse samples," Sharpless said. "So I combined data from my previous study with 34 other studies in order to determine how common it was in different groups." MHC CEUs

He looked at a total of 35 published studies from the past 50 years to find lifetime sleep paralysis rates. These studies surveyed a total of 36,533 people. Overall he found that about one-fifth of these people experienced an episode at least once. Frequency of sleep paralysis ranged from once in a lifetime to every night.

When looking at specific groups, 28 percent of students reported experiencing sleep paralysis, while nearly 32 percent of psychiatric patients reported experiencing at least one episode. People with panic disorder were even more likely to experience sleep paralysis, and almost 35 percent of those surveyed reported experiencing these episodes. Sleep paralysis also appears to be more common in non-Caucasians.

"Sleep paralysis should be assessed more regularly and uniformly in order to determine its impact on individual functioning and better articulate its relation to other psychiatric and medical conditions," said Sharpless.

He looked at a broad range of samples, and papers were included from many different countries.

People experience three basic types of hallucinations during sleep paralysis -- the presence of an intruder, pressure on the chest sometimes accompanied by physical and/or sexual assault experiences and levitation or out-of-body experiences.

Up to this point there has been little research conducted on how to alleviate sleep paralysis or whether or not people experience episodes throughout their lives.

"I want to better understand how sleep paralysis affects people, as opposed to simply knowing that they experience it," said Sharpless. "I want to see how it impacts their lives." Sharpless hopes to look at relationships between sleep paralysis and post-traumatic stress disorder in the future.

This research was supported in part by the National Institute of Mental Health.

Also working on this research was Jacques P. Barber, professor of psychiatry, University of Pennsylvania.