May 14, 2013
Depression Can Alter A Person’s Circadian Clock At The Cellular Level
redOrbit Staff & Wire Reports - Your Universe Online
The circadian clock rhythms that help govern biological, hormonal and behavioral patterns in the human body are altered at the cellular level in people suffering from depression, according to new research published in the Proceedings of the National Academy of Sciences (PNAS).According to the researchers, every cell in the human body operates on a 24-hour clock, with the brain serving as the timekeeper that helps keep things operating on the day-night/light-dark cycle that governs the world around us.
By doing so, it makes sure that our appetites, our sleep habits, our moods and more remain in sync with those around us. However, the study authors have now found evidence the clock could malfunction on a genetic level in those individuals who are suffering from clinical depression.
A team of researchers from the University of California Irvine (UCI), the University of California Davis, the University of Michigan, Cornell University, Stanford University and the Hudson Alpha Institute for Biotechnology made the discovery after reviewing data obtained from both depressed and non-depressed individuals.
They claim it is the first time direct evidence linking depression and altered circadian rhythms in the brain, and that it demonstrates that clinically depressed people are out of sync with the traditional daily cycle on a cellular level. With additional research, they believe their study could lead to improved diagnosis and treatment options for the condition, which affects more than 350 million people worldwide.
“Our findings involved the analysis of a large amount of data involving 12,000 gene transcripts obtained from donated brain tissue from depressed and normal people. We were amazed that our data revealed that clock gene rhythms varied in synchrony across six regions of normal human brain and that these rhythms were significantly disrupted in depressed patients,” senior author Dr. William Bunney, a professor of psychiatry and human behavior at UCI, said in a statement.
“The findings provide clues for potential new classes of compounds to rapidly treat depression that may reset abnormal clock genes and normalize circadian rhythms,” he added.
As part of their study, Dr. Bunney and his colleagues analyzed genome-wide gene expression patterns in the brain samples from 55 individuals, all of whom had no previous history of psychiatric or neurological illness. They were then compared to the expression patterns in samples from 34 severely depressed patients.
The researchers isolated several RNA samples from six regions of each brain, and arranged the gene expression data around a 24-hour cycle based on the subjects´ time of death. In each of the six brain regions, there were several hundred genes which demonstrated rhythmic patterns of expression over a 24-hour cycle, including many they said were vital to the body´s internal circadian rhythms.
Essentially, they were able to gain an intimate understanding of how a person´s genetic activity varied at different points throughout the day in each of the brain regions being analyzed. However, when they attempted to do the same in the brains of the 34 depressed individuals, they found the gene activity was off-schedule by several hours, and that the cells acted as if it was an entirely different time of day.
“There really was a moment of discovery,” said Jun Li, an assistant professor in the Department of Human Genetics at U-M, who led the analysis of the data generated by his colleagues. “It was when we realized 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.”
“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,” added Dr. Huda Akil, co-director of the U-M Molecular & Behavioral Neuroscience Institute. “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.”