Is this the link between sleep and depression?

The discovery of a genetic link between mood and the circadian rhythm may lead to treatments for depression, scientists say. Viviane Richter reports.

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Ask any new parent – trudging through weeks or months on too little sleep can have them in a foul mood. But science may have just worked out why, thanks to researchers at the US Howard Hughes Medical Institute.

They discovered a possible molecular link between mood and sleep which may one day lead to a treatment for depression or other mood disorders.

The team analysed the genomes of three extreme morning people – members of a family with “familial advanced sleep phase”, a sleep rhythm where people naturally wake up between 2:00 am and 5:30 am. These three individuals also reported signs of seasonal affective disorder, or the “winter blues” depressive symptoms during months with shorter days.

The scientists discovered each family member carried a mutation in a circadian rhythm gene coding for a protein called “PER3”.

“Everybody believes that there are connections between sleep and depression, but nobody has been able to find a biological link,” study author Louis Ptáček said.

“We think PER3 is a connection between pathways related to mood and the biological clock.”

To test the theory, the scientists genetically modified mice to carry the same, mutated form of PER3. When exposed to 12 hours of sunlight a day, these mice were active, scurrying on their running wheels around the same time as normal mice.

But when the team limited light exposure to four hours, the PER3-mutated mice suffered abnormal sleep patterns and became active hours after their counterparts, indicating the mutation shifted their circadian rhythm.

Next, the scientists gauged the mice’s mood by (short of mouse psychologists) dangling them by their tail. In this test, “depressed” mice give up struggling sooner than normal mice, passively hanging in defeat.

Sure enough, PER3-mutated mice stopped struggling sooner, indicating the mutation not only shifts the circadian rhythm but also causes depression in days of little sunlight.

What’s more, mice that completely lacked PER3 and were exposed to little sunlight appeared equally depressed. They stopped drinking sugar water, for instance, “not taking pleasure in something that is pleasurable”, explained Ptáček.

Whether PER3 has the same effects on mood and sleep in humans remains to be shown. But if it does, it may open a new way to control how we respond to changes in daylight.

The authors are hopeful it may one day lead to a treatment. “As we learn more, our understanding of the biology will allow us to be more rational in searching for drugs to treat, say, seasonal affective disorder,” said Ptáček.

The work was published in Proceedings of the National Academy of Sciences.

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Viviane Richter is a freelance science writer based in Melbourne.
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