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Mental Health, Sleep, and Circadian Rhythms

Exploring the genetics of circadian rhythms in sleep and mental illness.

Key points

  • Circadian rhythms are cycles that regulate almost everything in our bodies, telling us when to sleep, wake, and eat.
  • Circadian rhythm disruption can lead to mental and physical illness.
  • The genetics of circadian rhythms hold clues to causes of sleep problems and mental illness.

Sleep: Most of us spend about a third of our lives there, but many of us struggle to get into it, to get out of it—and, even, to define it. As the U.S. National Institutes of Health puts it, “Everyone needs sleep, but its biological purpose remains a mystery.” The details are vast and complicated, and we’re only beginning to understand them. What we do understand, however, has extensive implications for all of us— and perhaps especially for those with mental health conditions.

Why Circadian Rhythms Fascinate Me

Circadian rhythms are roughly 24-hour patterns in behavior and physiology, which are displayed by nearly every cell in all life forms. They affect everything from mood to body temperature to blood pressure to growth hormone to, yes, sleep. Circadian rhythms are created by molecular “clocks,” which sync our internal time with what’s going on around us.

Because our circadian system regulates nearly everything in our bodies, its disruption has major consequences on our physical—and mental—health. The complex molecular and genetic world that comprises the circadian system remains a frontier of exploration in neuroscience. We’ve made great progress in learning how genes influence our body clock, but how that affects sleep—and how it affects, and is affected by, our mental health is far more complicated and difficult to unravel. The opportunity to investigate some of these mysteries is what drew me to this area of research, especially because the potential to help people is so great.

What Is Sleep?

Sleep is a behavioral state that, scientifically, is defined in terms of slower waves in brain activity. It is, however, a complex behaviour involving multiple biochemical and neuronal circuits that work together in ways we don’t quite understand yet.

There are many catch-all terms that we often use casually in general conversation that actually refer to a complex set of things scientifically. Autism, for instance, used to be used as if it were one condition, when now we see it as a spectrum disorder. In past decades, we referred to finding “a” cure for cancer, as if cancer were only one disease with only one cause, when we now know that it’s, unfortunately, far more complicated. The idea of sleep is a bit similar. When you’re asleep, you haven’t simply switched off: Some of your brain is inactive, but other parts are (in fact, must be) active.

What Happens When We Disrupt Circadian Rhythms

In modern society, our circadian rhythms can be disrupted often. Whether you’re working on a factory line overnight or piloting a red-eye transatlantic flight, nursing an infant, or even just having a cup of coffee with breakfast, our bodies are often prompted to disregard information that tells it when to rest and when to be alert. Of course, many of these actions have mild effects.

But some people deal with more extensive dysregulation of their circadian rhythms outside of their control, with sleep disorders that create a mismatch between their sleep-wake pattern and the natural day and night cycle. One example is delayed sleep phase disorder, where people’s circadian rhythm is shifted later at night and later in the morning, making it difficult for them to fall asleep and wake up at “normal” times. Such profound disruptions can be extremely problematic: Studies have shown that the body’s inability to synchronise the sleep-wake cycle to their environment can lead to cognitive impairment, metabolic syndrome, and mental illness. Even this knowledge is surprisingly new.

The Unmet Medical Need of Sleep Disruption

At present, circadian rhythm disruption and sleep disruption have no good treatments. There are melatonin and melatonin agonists, but while melatonin is an excellent biomarker of the change—it’s an output of our body clock, and tracking it can help us track the changes of our circadian rhythms —it’s not terribly effective as a treatment for most people.

And there are sedatives and hypnotics, but those don’t provide the full restorative effects of natural sleep. If we can understand circadian rhythms genetically, we can begin to understand the pathways that they use—and, therefore, the pathways that new treatments could use. And this, perhaps, will draw us closer to understanding the complex world of sleep.

Circadian Rhythms and Mental Health: Cause? Effect? Both?

Circadian-rhythm dysregulation, and the abnormal sleep that goes with it, was once thought to just be a side effect of mental illness. They co-occur often, especially in conditions like depression, bipolar disorder, and schizophrenia. It was often thought that perhaps a person’s mental-health medication caused poor sleep or perhaps their distress led to disrupted sleep. Certainly, those things can happen.

Increasingly, however, we’re investigating the reverse: to what extent circadian rhythm disruption might actually be the cause, not the result, of some cases of mental illness. And a third possibility exists, too: Mental health conditions and sleep issues might, in some cases, both be caused by the same trigger. All three possibilities—or combinations of those possibilities—share the same hope: that the better we learn how to help to improve sleep, the more we can help to improve, or even eliminate, the concomitant mental health conditions.

Keeping Circadian Rhythms Healthy

Our circadian rhythms are regulated by many things: by light, by time, even by temperature. You probably have heard advice about minimizing your evening screen time and getting natural sunlight during the day, especially early, whether you’re crossing time zones or just hoping to be as alert as possible during your day. You’ve probably also heard advice about good sleep hygiene, keeping your bedroom dark, cool, and quiet. That’s all true and backed by science! We might not have untangled every mystery of sleep yet, but we’ve been able to determine many evidence-based ways to help people keep their circadian rhythms as healthy as possible.

However, many people with neuropsychiatric conditions are learning that their circadian rhythm abnormalities have deeper, sometimes genetic causes. My work, and that of my colleagues, is in this vein. We’re investigating the mechanisms that link circadian rhythms and sleep with mental health conditions and the genetics of circadian rhythms in sleep and in mental health.

For instance, we now know that there are circadian and clock-controlled gene mutations that have a role in the development of sleep, mental health, and metabolic disorders. We hope that our work will help us understand how these complex processes work, how they work together—and how we can better understand them and develop effective treatments that can solve, or even prevent, these distressing problems.

Used with permission
Professor Aarti Jagannath
Source: Used with permission

Professor Aarti Jagannath is an Associated Professor at the University of Oxford’s Sleep and Circadian Neuroscience Institute, as well as the Academic Cofounder of Circadian Therapeutics. Her group researches the fundamental neuroscience and molecular biology that underpins sleep and circadian rhythms—in particular, the mechanisms that regulate circadian clock entrainment. In addition to being a scientific researcher, Professor Jagannath is an entrepreneur, an educator, and an advocate for women in STEM. She holds fellowships from both the L’Oreal-UNESCO For Women in Science program as well as from the Biotechnology and Biological Sciences Research Council.


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