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
Researchers say the findings shed new light on what goes wrong in the brain
when depression strikes. And they hope the results, published 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.
How the study was done
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
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
"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.
Tracking the disorder
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
analyse 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.
Learn more about circadian
rhythms and health from the US. National Institute of General Medical