New Paths to Diagnosing Sleep and Circadian Rhythm Disorders with Phyllis Zee, MD, PhD: Research: Feinberg School of Medicine: Northwestern University

Episode summary

Approximately 70 million Americans suffer from sleep problems such as sleep apnea, insomnia, and restless legs syndrome. But doctors often overlook sleep-wake disorders in the circadian rhythm.

Phyllis Zee: “You present yourself as someone who may have insomnia, or someone who has hypersomnia, excessive daytime sleepiness, but it is actually due to a change or pathology in the circadian clock system.”

Everyone has an internal clock that produces circadian rhythms, intrinsic rhythms that last around 24 hours. They are not driven by cycles of light and dark; Instead, these rhythms are created at the molecular level. This circadian clock system exists in every single cell of the human body and is regulated by a genetic core mechanism of the clock. There are also more than 10 “clock genes” located in the cell nucleus that produce proteins that determine whether you are a “night owl” or a “morning lark”.

Phyllis Zee: “How quickly these proteins are broken down in the cytoplasm determines whether you will become an owl or a lark. So, if you’re an owl, it’s because your clock genetic system works a little slower than the 24-hour . If you’re a lark (your watch) is likely going a little faster. That is why larks wake up early because they have finished this circadian , this molecular circadian , a little faster than the rotation of the earth around its axis around the sun. “

Northwestern Medicine is home to the country’s first circadian medicine clinic. come for treatment from all over the world. Typical patients are younger adults who have had trouble sleeping since they were teenagers. Many cannot fall asleep until after 2 a.m. They cannot wake up on time for school or work, and many are diagnosed with psychological problems such as depression or anxiety. Once diagnosed, patients can be successfully treated with melatonin and blue light therapy.

Phyllis Zee: “I actually see physiology in play and I can say, ‘I think your melatonin rhythm will be at 4am instead of 9pm. Let’s try this. Let’s look at this! ‘ … you have the feeling of discovering something every day. “

Zee was part of a northwest team that recently developed the first simple blood test to determine a person’s exact internal time versus external time. The Time Signature test only requires two blood draws. Up to now, such precise measurements were only possible through costly and laborious hourly sampling over several hours.

Phyllis Zee: “This is a first step towards what I call a biomarker, a time-based biomarker for circadian timing, and not just for sleep.”

The blood test could advance personalized medicine and help doctors determine the best time of day for a person to take certain medications, such as blood pressure drugs and other drugs that target “clock genes”.

Phyllis Zee: “We can not only maximize the effectiveness, but also reduce the side effects of drugs.”

The most recent release on the time signature test is a proof of concept to show that it works, says Zee. The study was carried out on healthy young ; next it will move into patient populations.

Rosemary Braun, PhD, MPH, Assistant Professor of Preventive Medicine in the Department of Biostatistics, was the lead author of the study and Ravi Allada, MD, Professor of Neurobiology at the Weinberg College of Arts and Sciences in Northwestern and of Pathology in Feinberg, was a co-author. The study was published in the journal PNAS. Read more about the study.

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