If the early bird gets the worm, Susan Middlebrook should be well fed. Whether she wants to or not, she's ready to start each day between 1:30 and 3:00 a.m.

　　"I'm wide awake and ready to paint the house," the 49-year-old Colchester, Vermont, resident said. "I don't need a cup of coffee to get going, not at all. But between 4:00 and 5:00 [p.m.] you might have to nudge me with an elbow."

　　Middlebrook suffers from what is known as familial advanced sleep phase syndrome, or FASPS. Her body's clock is out of sync with the sleep-wake rhythm most of the world lives by. She goes to bed each night between 5:30 and 7:30 p.m. and wakes in the wee hours of the morning.

　　"The net result is you can feel very isolated," Middlebrook said. "Who wants to party at three in the morning? Nobody I know, and I'm not headed to the local bar to see who's still there." Instead, she quietly cleans the house, makes breakfast, or cuddles up with a book.

　　About three-tenths of a percent of the world's population lives like this, including two of Middlebrook's sisters, her daughter, and her mother. "Their whole clock is shifted," said Ying-Hui Fu, a neuroscientist at the University of California, San Francisco

　　Fu and colleagues report in tomorrow's issue of the science journal Nature on a newly discovered mutation to a single gene that they say causes FASPS.

　　The researchers are not yet certain how the gene mutation works to shift people's sleep time. But laboratory experiments suggest mutation slows the activity of a protein called casein kinase I delta (CKIdelta). "The next step is to figure out why," Fu said.

　　Carl Hunt directs the National Institutes of Health's National Center on Sleep Disorders Research in Bethesda, Maryland. He said the study "calls attention to the importance of individual genes in regulating sleep and, perhaps more importantly, in determining why some people have different sleep behaviors than other people."

　　There are more than a dozen tightly intertwined genes that control the human body clock, according to Fu. That clock controls a variety of physical and behavioral cycles. These include fluctuations in alertness, heart rate, blood pressure, and the immune system. Collectively, these cycles are known as circadian rhythms and are generally tied to the 24-hour day-night cycle.

　　In 2001 Fu and her colleagues discovered a different gene mutation that causes FASPS. But the researchers noted that the mutation was not common to all family members with advanced sleep phase syndrome. This led the team to search for additional genetic mutations.

　　In the new study, Fu and colleagues in San Francisco, Vermont, and Utah found the CKIdelta mutation in five members of a single family spread out over three generations.

　　In addition to FASPS, four of the five individuals showed signs of depression, Fu said.

　　"[The depression] is most likely caused by the same thing," she said. "As we probe deeper into how this mutation causes sleep problems, it very likely will also give insight to how the mutation will cause depression." Hunt, the NIH sleep disorders researcher, said the potential link between FASPS and depression is intriguing. But he adds that the current research is unclear on which comes first.

　　"People who have this syndrome are viewed by society as aberrations," he said. "The depression may be secondary to society's reaction to their sleep pattern."