Depression is a serious disorder with a high risk for suicide affecting approximately one in 10 Americans, according to the Centers for Disease Control, and is ranked as fourth of all diseases by the World Health Organization in terms of lifetime disability.
“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. The findings provide clues for potential new classes of compounds to rapidly treat depression that may reset abnormal clock genes and normalize circadian rhythms,” said Dr. William Bunney, the study's senior author, and Distinguished Professor of Psychiatry & Human Behavior at UC Irvine.
Circadian clock genes play an important role in regulating many body rhythms over a 24-hour cycle. Although animal data provide evidence for the circadian expression of genes in brain, little has been known as to whether there is a similar rhythmicity in the human brain.
In the study, the researchers analyzed genome-wide gene expression patterns in brain samples from 55 individuals with no history of psychiatric or neurological illness and compared them to the expression patterns in samples from 34 severely depressed patients.
The investigators isolated multiple RNA samples from six regions of each brain and arranged the gene expression data around a 24-hour cycle based on time of death. Several hundred genes in each of six brain regions displayed rhythmic patterns of expression over the 24-hour cycle, including many genes essential to the body’s circadian machinery.
In the end, they had a near-complete understanding of how gene activity varied throughout the day in the cells of the six brain regions they studied.“There really was a moment of discovery when we realized that many of the genes that we saw expressed 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,” said Jun Li, an assistant professor in the Department of Human Genetics at the University of Michigan who led the analysis of the massive amount of data generated by the rest of the team.
Tom Vasich | EurekAlert!
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