Research Finds New Ways to Diagnose “Sleep and Circadian Rhythm” Disorders
“Time signature, which is a blood test, is really a major breakthrough for my field and perhaps the first type of blood test that will have implications for how we treat and identify patients with sleep and circadian disorders.”
About 70 million Americans suffer from sleep problems such as sleep apnea, insomnia and restless leg syndrome. But physicians often miss circadian rhythm sleep-wake disorders.
Phyllis Zee: “They present like somebody who may have insomnia or somebody who may have what we call hypersomnia, excessive daytime sleepiness, but it’s actually due to an alteration or pathology in the circadian clock system.”
Everyone has an internal clock that produces circadian rhythms, intrinsic rhythms that keep a time of approximately 24 hours. They’re not driven by light-dark cycles; instead, these rhythms are generated at a molecular level. This circadian clock system exists in every single cell of the human body and is regulated by a core clock genetic mechanism. There are also more than 10 “clock genes” that reside in the nucleus of cells and produce proteins that determine whether you are a “night owl” or “morning lark.”
Phyllis Zee: “How quickly these proteins get degradated in the cytoplasm determines whether you’re going to be an owl or a lark. So if you’re an owl, it is because your clock genetic system is taking a little slower than the 24-hour cycle. If you’re a lark (your clock) is probably going a little faster. That’s why larks wake up early, because they finished that circadian cycle, that molecular circadian cycle, a little faster than the rotation of the earth on its axis around the sun.”
Northwestern Medicine is home to the first circadian medicine clinic in the country. People come from around the world for treatment. Typical patients are younger adults who have had problems sleeping since their teenage years. Many cannot fall asleep until after 2 a.m. They can’t wake up in time for school or work and many end up being diagnosed with mental health issues such as depression or anxiety. After a diagnosis, patients can be treated successfully with melatonin and blue light therapy.
Phyllis Zee: “I actually see physiology in play and I can say, ‘I think your melatonin rhythm is going to be at 4 a.m. instead of 9 p.m. Let’s sample this. Let’s take a look at this!’ … you feel like every day you’re discovering something.”
Zee was part of a Northwestern team that recently developed the first simple blood test to identify individuals’ precise internal clock times as compared to external time. The test, Time Signature, requires only two blood draws. Previously, measurements this precise could only be achieved through a costly and laborious process of taking samples every hour over a span of multiple hours.
Phyllis Zee: “This is a first step towards providing what I call a biomarker, a time based biomarker, for circadian timing, and it isn’t just for sleep.”
The blood test could advance personalized medicine and help physicians determine the best time of the day for a person to take certain medications, such as blood pressure medication, and other medications that target “clock genes.”
Phyllis Zee: “We can maximize not just the effectiveness, but also decrease the side effects of medications.”
The recent publication about Time Signature test is a a proof of concept, to show that it works, Zee says. The study was done in healthy young people; next it will move into patient populations.