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The link between sleep, genes, and mental health

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Posted March 7, 2019

We’ve known for some time that sleep can affect a person’s risk for developing mental health problems. New research from Penn Medicine and a host of other institutions and organizations shows that whether you stay up until the wee hours or bound out of bed with the first rays of sunshine matters, too.

Philip Gehrman, an associate professor in Penn’s Department of Psychiatry, studies insomnia and the genetic link between sleep and psychiatric disorders. He contributed to the recent work, which was published in the journal Nature Communications

A sleeping car driver. Image credit: pxhere.com, CC0 Public Domain

A sleeping car driver. Image credit: pxhere.com, CC0 Public Domain

The genome-wide association analysis compared the chronotypes of almost 700,000 people. The idea was to better understand participants’ circadian rhythm, circadian “preference” for going to bed late or waking early, and the effect on mental health. Penn Today spoke with Gehrman about the findings, which showed that being a morning person lowered a person’s risk for schizophrenia and other similar disorders.

Most people have heard of circadian rhythm but may not fully understand it. Can you explain it?

Circadian rhythms are these roughly 24-hour rhythms in our body. Almost everything in our body follows our daily circadian rhythm, but the timing can vary from person to person. Some people are night owls, meaning their rhythms are later. Other are what we call a lark, more of a morning person, and a lot of people are just in the middle, they’re neither extreme. Something called a chronotype is a person’s overall circadian tendency, and there’s a long history showing that chronotype can be associated with a range of health outcomes. In particular, being a night owl, especially an extreme night owl, is linked to greater risk of having mental health problems.

Are there standard definitions for ‘night owl’ and ‘morning lark’?

Not really. There are no hard cutoffs, like if you go to bed after X p.m., you’re now considered a night owl. There’s a lot of subjectivity to it.

You described this study as a genome-wide association analysis. What does that mean?

It means we were trying to understand the genetic variation that might explain where someone’s chronotype comes from. To do this, you need large sample sizes. We had access to two datasets, one from the U.K. Biobank, which is a population-based study in the United Kingdom of half a million people, and data from 23andMe, the direct-to-consumer genotyping service. In both situations, participants were asked a single question about whether they’re more of a morning or night person. We looked at their answer and their genetic data.

Then the question became what does this information mean? For example, being a morning person may be associated with a certain gene, but that doesn’t mean that gene causes someone to be a morning person. Also, we have 3.3 billion pieces of DNA and we looked about 11.5 million genetic variants, which is a small subset. When you get results, one of the big questions is what’s the actual gene involved? It is the one next door? A few genes away? That’s one of the biggest difficulties.

What did the study reveal in terms of sleep patterns, genes, and mental health?

What I’ve described so far is the process for finding the genetic variants associated with being a morning or a night person. Then you do what’s called Mendelian randomization, which is a statistical approach that basically treats someone’s genotype as if it were randomly assigned. By doing this, you can say of all the genetic variants we found, what’s the relationship between morning-ness and some other trait or condition? In this case, we found that being a morning person was associated with lower risk for, in particular, schizophrenia, but also for mental health conditions overall.

What does this mean for people who tend to stay up later?

I don’t want people who are night owls to think, ‘I’m definitively going to develop schizophrenia.’ Yes, being a night owl is associated with worse mental health, but most night owls will not end up needing psychiatric help.

Is it true that once a night owl, always a night owl? Or can this behavior pattern change?

There are two main drivers of your chronotype. One is genetics. ‘I’ve always been a night owl. Even when I was a little kid, my parents say I stayed up later than they did.’ When it’s genetically driven, it’s more of a lifelong trait, making it harder to change. But in another group, it’s behaviorally produced. ‘Twenty years ago, I used to work the night shift, but I’m still stuck in that sleep pattern.’ That’s generally easier to adjust, and we do that by putting people on certain sleep schedules or using environmental cues like seeing sunlight at certain times of day.

What’s next for this research?

This is just the starting point. We have a four-year NIH-funded study that has three parts. My role is to mine the databases to determine which genetic variants are associated with insomnia or chronotype. A collaborator at the Children’s Hospital of Philadelphia will then use neural progenitor cells to help pinpoint more clearly which genes are being impacted. The genes we feel most confident about will go to a collaborator at Florida Atlantic University who studies sleep in fruit flies. He can manipulate and measure their sleep and circadian rhythms to determine what effects altering them has. We’ll have started with hundreds of candidates and hopefully, we’ll narrow it down to a few genes by the end of the study.

How does this work fit in with your overall research interests?

My broad interest is in the relationship between sleep, circadian rhythms, and mental health. I primarily focus on insomnia, which is linked with mental health in a number of different ways. A lot of my work has been at the VA in veterans with post-traumatic stress disorder. We’re doing a study of depression right now and just finished one of patients with psychosis. The idea is this: When your sleep is disturbed, it increases your risk for mental health problems, and when you have a mental health problem, disturbed sleep seems to make it worse.

Source: University of Pennsylvania

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