The researchers used gene expression patterns to try to predict the time of death for each person in the study (inner circles), and then compared it with the actual time of death (outer circles). The two matched closely in healthy people, as shown by the short lines between the two points in the left diagram. But in depressed people, the two were out of sync, as seen with the longer lines at right. (Courtesy University of Michigan)

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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.

Its 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. The findings, in the Proceedings of the National Academy of Sciences, come from scientists from the University of Michigan Medical School and other institutions.

The discovery was made by sifting through massive amounts of data gleaned from donated brains of depressed and non-depressed people. With further research, the findings could lead to more precise diagnosis and treatment for a condition that affects more than 350 million people worldwide.

Whats more, the research also reveals a previously unknown daily rhythm to the activity of many genes across many areas of the brain expanding the sense of how crucial our master clock is.

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 patients day pattern of gene activity could look like a night pattern and vice versa.

The work was funded in large part by the Pritzker Neuropsychiatric Disorders Research Fund, and involved researchers from the University of Michigan, University of Californias Irvine and Davis campuses, Weill Cornell Medical College, the Hudson Alpha Institute for Biotechnology, and Stanford University.

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.

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ANN ARBOR: Brain study shows internal clocks of depressed people are altered at cell level

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