In a paper published online this afternoon in Proceedings of the National Academy of Sciences, researchers provide for the first time direct evidence that the brain's master clock is disrupted in people with depression. A University of Michigan release offers these details:
The team uses material from donated brains obtained shortly after death, along with extensive clinical information about the individual. Numerous regions of each brain are dissected by hand or even with lasers that can capture more specialized cell types, then analyzed to measure gene activity. The resulting flood of information is picked apart with advanced data-mining tools.
Lead author Jun Li, Ph.D., an assistant professor in the U-M 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.
The study authors, which include Stanford's Alan Schatzberg, MD, PhD, say that having knowledge of these altered circadian rhythms could help with the diagnosis and treatment of depressive disorders. "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,” Michigan's Huda Akil, PhD, explained.
