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UCSF study offers insight into human circadian rhythms

The scientists do not know what accounts for the difference.

"The findings suggest that, although many individual parts of the circadian rhythm clock are conserved across species, fundamental differences exist," says the first author of the study, Ying Xu, PhD, a visiting postdoctoral fellow in the Fu lab. "These models provide the opportunity to begin study of the similarities and differences between circadian clocks in model organisms and humans."

While the internal clock of most people operates in just over a 24-hour time period, the clock of those with FASPS advances an average of 45 minutes a day. If left unchecked, it would continue to speed up. Due to the social demands and needs of those with the disorder, it is kept in check to a relative degree.

The creation of the transgenic mouse model provides a tool for exploring how the CK1 delta-T44A enzyme causes FASPS. It also offers a model for testing promising compounds directed at the enzyme to treat a variety of sleep disorders, whether resulting from biological or environmental factors.

While FASPS is caused by an individual gene, other forms of sleep-pattern disturbances, such as the tendency for some elderly to wake up earlier than normal ("advanced sleep phase syndrome"), could be caused by "epigenetic" factors, which involve changes in gene expression rather than a mutation in a gene.

Finally, the potential insights extend beyond those involving sleep. Four of the five individuals in the study have clinical features or a history of depression. While the scientists say that this could be a coincidence, or that the depression is situational, i.e., due to being "out of phase with the rest of the world," the more provocative possibility, they say, is that circadian rhythm variants contribute to psychiatric disorders.

Now, in collaboration with UCSF's Larry Tecott, MD, PhD, UCSF associate professor of psychiatry and a member of the UCSF Center for Neurobiology an
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
30-Mar-2005


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