Understanding Depression

Genetic brain differences could shed light on treating depressive disorders

Individuals with severe clinical depression who died while they were depressed had lower levels of molecules called fibroblast growth factors, and associated receptors, in their brains than people without the disease, or those with the bipolar form of depression, according to a study by U-M researchers.

The intensity of colors in this microarray data from the Pritzker Consortium study represents the level of activity of specific genes in brain tissue. Photo: Simon Evans, U-M Molecular & Behavioral Neuroscience Institute

Since fibroblast growth factors have never been associated with psychiatric illness before, the discovery 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 results of the study were published in the Proceedings of the National Academy of Sciences by researchers from the Pritzker Neuropsychiatric Disorders Research Consortium. The research team consisted of scientists from the University of Michigan Molecular & Behavioral Neuroscience Institute, formerly known as the Mental Health Research Institute, and researchers from the University of California and Stanford University.

“This finding comes from an unbiased search to find which 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. “The family of genes that was most different and showed the highest significance as a coherent group was the fibroblast growth factor family.”

Fibroblast growth factors stimulate cell growth in many areas of the body and are involved in the growth of multiple tissues at various stages of life. They have potent effects during embryonic, fetal and child development, and can modify the size and structure of particular brain regions. They are also involved in the repair of adult tissues after injury and may mediate the cross-talk between different cell types in the brain.

As a result, they can be seen as mediators of a property that neuroscientists call “neural plasticity” — the ability of the brain to adapt to stress, experience, disease and the effects of drugs.

“We can’t say whether these growth factor gene expression changes are a predisposing factor for depression or a consequence of the disease process itself,” says Simon Evans, Ph.D., U-M research investigator. “There may be people out there with compromised fibroblast growth factor systems, but if they don’t experience stressful life events they may never develop major depression. We need to study the system further to unravel the answer to this question.”

—KG

For an expanded version of the story:
www.med.umich.edu/opm/newspage/2004/depressedbrains.htm

For patient information about depression:
www.med.umich.edu/depression