Depression: Patients Body Clocks are Altered at Cell Level

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. 

Credit: Image courtesy of University of Michigan Health System

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.

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.

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.

What's 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 patient's "day" pattern of gene activity could look like a "night" pattern -- and vice versa.

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Journal Reference:

1. Jun Z. Li, Blynn G. Bunney, Fan Meng, Megan H. Hagenauer, David M. Walsh, Marquis P. Vawter, Simon J. Evans, Prabhakara V. Choudary, Preston Cartagena, Jack D. Barchas, Alan F. Schatzberg, Edward G. Jones, Richard M. Myers, Stanley J. Watson, Jr., Huda Akil, and William E. Bunney. Circadian patterns of gene expression in the human brain and disruption in major depressive disorder. PNAS, 2013 DOI: 10.1073/pnas.1305814110