Characterization of Circadian Rhythm Disorders
Our Research
Our research focuses on the genetics of inherited sleep disorders in families. In 2001, our research team reported the first morning-person "sleep gene" by comparing the sleeping patterns and DNA of many individuals from the same family1. The gene is called hPer2 and family members carrying a variant form of this gene showed a striking "morning lark" sleeping pattern; falling asleep around 7:00 p.m. in the evening and waking up around 4:00 a.m. the next morning. This sleeping pattern is termed Familial Advanced Sleep Phase Syndrome (FASPS). In 2005, our research team reported a second circadian sleep gene called CK1d that also was shown to cause FASPS2. This gene was similarly found by comparing the sleeping patterns and DNA of many individuals from the same family. More recently in August of 2009, our research group reported the first circadian sleep gene implicated in short sleep in humans. The gene is called DEC2 and family members carrying a variant form of this gene were shown to be life-long "natural short sleepers;" requiring only 6 - 6.5 hours of sleep each night3. Once again, this gene was found by comparing the sleeping patterns and DNA of several individuals from the same family.
Our goal is to discover new sleep genes in families with sleep problems. The information gained from such discoveries will provide an improved basic science understanding of the genetic influences on sleep. In addition, sleep genes have been implicated in other conditions such as depression and cancer. Practical applications of such understanding may include better treatment options for sleep disorders, psychiatric conditions, and cancer.
What Does Study Participation Involve?
The total time it will take to participate in this study is approximately 2 hours. To be scientifically useful, participation will include the following:
1. Reading and signing our research consent form
2. Filling out 5 sleep questionnaires about your personal sleeping pattern, mood, and activity level. These can be completed and returned electronically through email.
3. Having an approximately 30-45 minute phone conversation to clarify and expand upon your sleep questionnaire answers
4. Donating a DNA sample so we can compare your DNA to the rest of your family. The preferred DNA sample is a standard blood draw similar to the type routinely taken at a doctor's office. If any participant is uncomfortable giving blood, saliva is also OK.
As this is a genetic research project, we will be seeking participation from as many direct and extended members of your family as possible.
Contact Information
We are currently researching families with extreme "morning lark" sleeping patterns (Familial Advanced Sleep Phase Syndrome: FASPS), extreme "night owl" sleeping patterns (Delayed Sleep Phase Syndrome: DSPS), and life-long "natural short sleepers." If you feel that your family has a history of any of these sleeping patterns we would be very interested to hear from you and discuss the possibility of your participation in our research. Please contact our clinical research coordinator via email or phone if you would be interested in participating in this study:
Brian Curtis
University of Utah, Department of Neurology
Clinical Study Assistant, Sleep-Wake Center
375 Chipeta Way, Ste A200
Salt Lake City, UT 84108
Phone: 801-581-8865
Fax: 801-587-3349
Email: brian.curtis@hsc.utah.edu
Below are a few brief descriptions of the circadian sleep disorders we are currently studying:
Familial Advanced Sleep Phase Syndrome (FASPS)
Advanced Sleep Phase Syndrome (ASPS) is called a circadian rhythm condition because the daily rhythm of sleep and wake occur at an advanced (earlier) time of day. In other words, people with ASPS fall asleep early and wake up early. People with ASPS often think of themselves as "morning people" because they function better early in the day. This type of sleep and activity pattern seems to be genetic in most cases and can be obvious to the parents even when their child is still quite young. ASPS is unusual compared to the more common tendency to stay up late and sleep in late on vacations or other times when early morning social responsibilities are less pressing.
Some people with ASPS do not like the early morning awakenings. However, ASPS is not considered a disease or debilitating disorder. Many people with ASPS lead perfectly normal lives; they just schedule their activities earlier in the day. Even though ASPS is not a disease, people and families with ASPS can still teach medical science a great deal about how genes and the brain influence sleep. We are interested in ASPS because a better understanding of the genetics of sleep may lead to better treatment options for people who have sleep problems
Familial Delayed Sleep Phase Syndrome (FDSPS)
Delayed Sleep Phase Syndrome (DSPS) is also a circadian rhythm disorder but these individuals are on the opposite spectrum of sleep and wake compared to individuals with ASPS. In other words, people with DSPS fall asleep late and wake up late the next day. People with DSPS often think of themselves as "night owls" because they begin to get tired later in the evening (or in the early morning) and function better later the next day. This type of sleep and activity pattern seems to be genetic in most cases and can be obvious to the parents even when their child is still quite young. DSPS seems to be far more common in the general population than ASPS. In rare cases, individuals can be so delayed that their sleep pattern is not influenced by the solar day/night cycle. These individuals sleep and wake solely on their own biological "clock" and typically fall asleep about 1 hour later each day. For example, they might fall asleep at 10:00 p.m. one night, 11:00 p.m. the next night, midnight the night after, and so on. This is known as "Circadian Rhythm Sleep Disorder: Free-Running Type" or Non-24 Hour Sleep Wake Syndrome.
Many people with DSPS do not like their late morning or afternoon awakening as it greatly interferes with social morning responsibilities such as school and work. For this reason DSPS is considered a "sleep disorder" as it can have a negative impact on these individuals' lives. Often these individuals have been told by family, friends, and coworkers that they are simply "lazy" or unwilling to adhere to a more "typical" sleep and wake schedule. We are interested in DSPS because a better understanding of the genetics of this disorder may lead to better treatment options for DSPS individuals and allow them to more effectively cope with early morning responsibilities.
Natural Short Sleepers
It has been reported that humans need from 7.5 - 8 hours of sleep each night for optimal functioning. Chronic sleep deprivation can lead to impaired health, thinking, memory, and the ability to perform tasks such as driving an automobile. Some individuals claim to get by just fine on 5 - 6 hours of sleep each night (or less). However, many of these individuals require a "power nap" during the day, or are chronically fatigued from their lack of sleep.
In August of 2009, our research group reported the first circadian sleep gene implicated in short sleep in humans. The gene is called DEC2 and family members carrying a variant (mutant) form of this gene were shown to be life-long "natural short sleepers;" requiring only 6 - 6.5 hours of sleep each night3. What was surprising about these individuals was that despite their short sleep times, they were full of energy and more active than those members of their family getting around 8 hours of sleep per night. The same sleep and activity pattern was observed in both mice and flies carrying the variant form of the DEC2 gene. This family presents a rare scientific opportunity to learn more about how our genetics can influence the amount of sleep we can get each night. It is our goal to uncover additional genes regulating sleep length by enrolling families that show a similar pattern of life-long short sleep. These findings will provide an improved basic science understanding of the genetic regulation of sleep-length and ultimately may lead to better treatment options for people who have sleep problems.
Selected Publications - Full Articles
References:
1. Toh KL, Jones CR, He Y, Eide EJ, Hinz WA, Virshup DM, Ptacek LJ, Fu YH. (2001). "An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome." Science 291: 1040-3.
2. Xu, Y., Padiath, Q.S., Shapiro, R.E., Jones, C.R., Wu, S.C., Saigoh, N., Saigoh, K., Ptacek, L.J. Fu, Y-H. (2005) "Functional consequences of a CKId mutation causing familial advanced sleep phase syndrome". Nature 434: 640-44.
3. He Y., Jones, C.R., Fujiki, N., Xu Y., Guo B., Holder Jr. J.L., Rossner, M.J., Nishino S., Fu Y-H. "The transcriptional repressor DEC2 regulates sleep length in mammals." Science 325: 866-70
