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Daily Gene Rhythms May Be Off in Depressed People

Study found 'clock' in brain was disrupted in autopsies of those who suffered mental disorder at time of death

By Amy Norton
HealthDay Reporter

MONDAY, May 13 (HealthDay News) -- Just like you, the genes in your brain follow a daily routine. But that natural rhythm may be thrown off in people with depression, a new study suggests.

Researchers say the findings shed new light on what goes wrong in the brain when depression strikes. And they hope the results, published online Monday in the journal Proceedings of the National Academy of Sciences, could spur new therapies down the road.

It has long been known that your body processes follow daily circadian rhythms, and that the "master clock" orchestrating it all exists in the brain. That clock mainly responds to light and darkness in your surroundings.

Scientists have also thought that gene activity in animals' brains follows a daily ebb and flow. But seeing whether that's true in the human brain is a lot tougher, said researcher Huda Akil.

If you want to look for daily rhythms in hormone activity, Akil said, you can take multiple blood samples from the same people over the course of 24 hours. You cannot, however, investigate the brain that way.

To get around the problem, Akil's team studied autopsied brain tissue from 89 people who had died at different times of day. That way, they could look at each person's gene activity at the time of death and search for differences from one individual to the next.

"Hundreds of genes emerged as having a rhythm based on the time of day," said Akil, a professor of neuroscience and psychiatry at the University of Michigan in Ann Arbor.

That rhythm was clear in brain tissue from the 55 people with no history of psychiatric disorders. Akil said her team was able to look at an individual's gene activity and correctly guess that person's time of death within an hour.

They could not, however, do that for the 34 individuals who were suffering from major depression at the time of death. Their gene activity patterns were too varied.

"This is very clear evidence that the 'clock' in the brain is disrupted in depression," Akil said.

That makes sense, since doctors and researchers have long seen signs of a disturbed circadian rhythm in people with depression, said Eva Redei, a professor of psychiatry at the Northwestern University Feinberg School of Medicine in Chicago.

Those signs, Redei said, include sleep problems -- like sleeping too much or too little -- and abnormal activity in the "stress hormone" cortisol, which follows a daily rhythm. There also is a form of depression known as seasonal affective disorder (SAD) in which people suffer symptoms during the short days of winter but feel better during the sunnier seasons.

Experts do not know the precise cause of SAD, but Redei said it involves problems with the circadian rhythms.

This study, Redei said, "very nicely proves" that a disruption in the brain's daily gene activity exists in depression.

Both she and Akil said a big unknown is whether out-of-sync brain genes are an initial cause of depression or a result of the disorder.

Either way, Akil said she thinks the out-of-sync genes would feed people's symptoms. Think about how bad you feel, she said, when the body's normal rhythms are thrown off due to jet lag.

In the future, Akil said, the findings might help lead to new "biomarkers" for diagnosing depression or tracking how well the disorder is responding to treatment. But first, Redei said, researchers would have to see if the altered gene activity in the brain correlates with something doctors can actually measure -- such as something they can see in brain imaging or something they can analyze in the blood.

The findings might also help identify new "molecular targets" for depression treatment, Akil said.

Right now, antidepressant drugs target certain chemicals in the brain believed to contribute to depression -- most famously, the mood-regulating chemical serotonin. But Akil said the new findings show that there are multiple things going wrong in the brain when a person has major depression.

"It's not only a serotonin imbalance," she said.

More information

Learn more about circadian rhythms and health from the U.S. National Institute of General Medical Sciences.


SOURCES: Huda Akil, Ph.D., professor, neuroscience and psychiatry, University of Michigan, Ann Arbor; Eva Redei, Ph.D., professor, psychiatry, Northwestern University Feinberg School of Medicine, Chicago; May 13-17, 2013, Proceedings of the National Academy of Sciences, online

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