Researchers have determined why some people struggle to fall asleep.
A research team at The Rockefeller University have discovered that a variant of the gene CRY1 slows the internal biological clock—called the circadian clock—that normally dictates when you feel sleepy each night and when you are ready to wake up.
The mutation is considered dominant, meaning that having just one copy of it can cause a sleep disorder.
People with the “night owl” variant of this gene have a longer circadian cycle than most, which makes them stay awake later.
“Compared to other mutations that have been linked to sleep disorders in just single families worldwide, this is a fairly impactful genetic change,” senior author Michael Young, the Richard and Jeanne Fisher Professor and head of Rockefeller’s Laboratory of Genetics, said in a statement.
According to the research, as many as one in 75 people in some populations may have the mutation.
The Centers for Disease Control and Prevention estimates that between 50 and 70 million adults in the U.S. have a sleep or wakefulness disorder, ranging from insomnia to narcolepsy, which can predispose people to chronic diseases such as diabetes, obesity and depression.
People who self-categorize as night owls are often diagnosed with delayed sleep phase disorder (DSPD), meaning their 24-hour sleep-wake cycle is delayed, making them energetic long after most people have fallen asleep.
Most people with DSPD are forced to wake up before their bodies tell them to in order to make it to work or school on time, leading not only to insomnia early in the night but also fatigue during the day.
Young’s lab has studied the circadian clock for more than 30 years, identifying a number of the genes involved in keeping flies, humans and other animals on schedule when it comes to eating and sleeping.
During the most recent research Young and research associate Alina Patke, the first and co-corresponding author of the paper, collaborated with sleep researchers at Weil Cornell Medical College. They examined subjects who were asked to spend two weeks in a laboratory apartment that was isolated from all cues to the time of day, eating and sleeping whenever they were inclined.
The majority of people will follow a roughly 24-hour sleep-wake cycle when put in such a free-run environment but a DSPD subject not only stayed up later but had a cycle that was about 30 minutes longer.
Also, changes in body temperature and hormones that cycle along with the circadian clock—including melatonin, which helps regulate sleep—were also delayed.
“Melatonin levels start to rise around 9 or 10 at night in most people,” Young said. “In this DSPD patient that doesn’t happen until 2 or 3 in the morning.”
In a healthy circadian clock, a handful of genes turn on and off over a 24-hour cycle but the protein made by CRY1 is normally responsible for suppressing some of the genes during certain parts of the cycle.
However, Young and Patke discovered the mutation identified in the patient made the CRY1 protein more active than usual, keeping other clock genes switched off for a longer period of time.
The researchers also reached out to other members of the patient’s family and discovered five relatives who shared the mutation, all of which had signs of DSPD or a history of persistent sleep problems.
The researchers will now examine how they can use this discovery to help patients suffering from DSPD.
“Just finding the cause doesn’t immediately fix the problem,” Patke said. “But it’s not inconceivable that one might develop drugs in the future based on this mechanism.”
Future studies are planned to work out whether CRY1 mutations also affect the metabolic cycles of people with DSPD, since the human circadian cycle is known to not only regulate but also hunger and levels of metabolites and hormones.
The study was published in Cell.