A New Culprit In Depression?

A New Culprit In Depression? Study Finds Surprising Differences In Gene Activity In The Brains Of Depressed People

The brains of people with severe depression have lower levels of several related molecules that are key to the development, organization, growth and repair of the brain than the brains of people without the disease, or those with the bipolar form of depression, a new study finds.

The discovery, which surprised researchers in the multi-university consortium that made it, suggests a whole new direction for understanding depression and developing new depression treatments. It may even help scientists understand how some antidepressant medications work in the brain to ease symptoms, and why there is wide variation in how depressed people respond to different antidepressants.

The finding was made in two specific areas of the brain known to be important to depression. The study relied on microarray analysis of 32 post-mortem brain samples - the microarray method can simultaneously measure the level of activity of tens of thousands of genes that are functional in a given tissue.

The researchers found that levels of molecules called fibroblast growth factors (FGFs), and two of the receptors that bind to them, were significantly lower among people who had been diagnosed with severe clinical depression and had died in a depressed state. There was also some indication that those depressed people who had been taking antidepressants before their deaths had levels of FGF and FGF receptors that were closer to normal.

The results are published online this week in the early edition of the Proceedings of the National Academy of Sciences by researchers from the Pritzker Neuropsychiatric Disorders Research Consortium, which is supported by the Pritzker Family Philanthropic Fund and by the National Institute of Mental Health. The research team consisted of scientists from the University of Michigan's Mental Health Research Institute and Department of Psychiatry, working in close collaboration with researchers from the University of California's Davis and Irvine campuses and from Stanford University.

"This finding comes from a completely unbiased search that began with no hypothesis, to find what genes best differentiate major depression brains from normal and bipolar brains," says senior author Huda Akil, Ph.D., the Gardner C. Quarton Distinguished Professor of Neurosciences in Psychiatry at U-M. "A wide set of individual genes came up as different between the depressed and control individuals, but the family of genes that was most different and showed the highest significance as a coherent group was the FGF family. This suggests a more profound change in an entire system of communication and control within the brain."

No previous studies have directly examined the role of FGFs or their receptors in psychiatric illnesses. Another growth factor, called Brain Derived Neurotrophic Factor, has been hypothesized to play a role in the effects of stress on the brain and in the mode of action of antidepressants.