Natural Health News — Every cell in our bodies runs on a 24-hour clock, tuned to the night-day, light-dark cycles that have ruled us since the dawn of humanity.
The brain acts as timekeeper, keeping the cellular clock in sync with the outside world so that it can govern our appetites, sleep, moods and much more.
But new research shows that the clock may be broken in the brains of people with depression – even at the level of the gene activity inside their brain cells.
Researchers, reporting in the Proceedings of the National Academy of Sciences say it’s the first direct evidence of altered circadian rhythms in the brain of people with depression, and shows that they operate out of sync with the usual ingrained daily cycle.
A “stopped clock”
In a normal brain, the pattern of gene activity at a given time of the day is so distinctive that the authors could use it to accurately estimate the hour of death of the brain donor, suggesting that studying this “stopped clock” could conceivably be useful in forensics.
By contrast, in severely depressed patients, the circadian clock was so disrupted that a patient’s “day” pattern of gene activity could look like a “night” pattern – and vice versa.
In a fascinating study, researchers from the University of Michigan and several other institutions across the US, used cells from donated brains donated by depressed and non-depressed people and obtained shortly after death. Researchers also had access to extensive clinical information about the individuals.
Lead author Jun Li, PhD, an assistant professor in the University of Michigan Department of Human Genetics, describes how this approach allowed the team to accurately back-predict the hour of the day when each non-depressed individual died – literally plotting them out on a 24-hour clock by noting which genes were active at the time they died. They looked at 12,000 gene transcripts isolated from six regions of 55 brains from people who did not have depression.
This provided a detailed understanding of how gene activity varied throughout the day in the brain regions studied. But when the team tried to do the same in the brains of 34 depressed individuals, the gene activity was off by hours. The cells looked as if it were an entirely different time of day.
A moment of discovery
“There really was a moment of discovery” says Li. “It was when we realised that many of the genes that show 24-hour cycles in the normal individuals were well-known circadian rhythm genes – and when we saw that the people with depression were not synchronized to the usual solar day in terms of this gene activity. It’s as if they were living in a different time zone than the one they died in.”
The findings go beyond previous research on circadian rhythms, using animals or human skin cells, which were more easily accessible than human brain tissues.
“Hundreds of new genes that are very sensitive to circadian rhythms emerged from this research – not just the primary clock genes that have been studied in animals or cell cultures, but other genes whose activity rises and falls throughout the day,” says co-author and co-director of the University of Michigan Molecular & Behavioral Neuroscience Institute, Huda Akil, PhD.
“We were truly able to watch the daily rhythm play out in a symphony of biological activity, by studying where the clock had stopped at the time of death. And then, in depressed people, we could see how this was disrupted”.
The challenge of determining why the circadian clock is altered in depression still remains. “We can only glimpse the possibility that the disruption seen in depression may have more than one cause. We need to learn more about whether something in the nature of the clock itself is affected, because if you could fix the clock you might be able to help people get better”, Akil notes.
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