Scientists find new clues underlying mood disorders

Certain genes are expressed differently in people with depression

Researchers have found altered gene activity in people who suffer from major depression, a discovery that may one day help doctors better diagnose and treat the condition. The research, conducted by a consortium of four universities, appears this week in the online edition of the Proceedings of the National Academy of Sciences USA (PNAS). Scientists found that the fibroblast growth factor system, which is a family of proteins involved in the growth, development and maintenance of nerve cells, had an overall decrease in levels in patients who had major depressive disorder. Proteins are the products of gene expression.

“This study is the first to implicate this particular family of gene products in major depression,” said Edward G. Jones, professor of psychiatry and director of the Center for Neuroscience at UC Davis and a principal investigator of the study. “The fibroblast growth factor system is now important to consider when looking for causes of mood disorders.”

Growth factors bind to receptors on the surface of cells, setting in motion a variety of biological activities. The fibroblast growth factors are critical during brain development and also help maintain the central nervous system in adulthood.

The scientists applied microarray technology, a powerful new tool used to create gene expression profiles, to biological samples from specific areas of the brain at autopsy. Recently deceased people who had suffered from major depressive disorder or bipolar disorder were compared to controls who had no mood disorder. Those with major depressive disorder had different amounts of fibroblast growth factors than the controls. Those with bipolar disorder did not show these differences.

Interestingly, subjects with major depression who had been treated with selective serotonin reuptake inhibitors (SSRIs), a common medication for depression, showed smaller changes in the fibroblast growth factor system than those who had not been treated. “The fact that fibroblast growth factors were not as altered in individuals treated with SSRIs suggests that these drugs may act on this system and may be responsible for alleviating symptoms of depression,” said Jones, who is an authority on brain anatomy and is recognized as a leading researcher of the central nervous system. “Knowing this may help guide future pharmaceutical development.”

Information gleaned from specific genetic profiles, however, can help pinpoint what biological mechanisms are impaired so that more specific drugs with fewer side effects can be developed, according to Jones. “Targeted therapeutics made possible by these new technological approaches offer the dream of ’personalized medicine,’ in which knowing each person’s genetic make-up can help determine how he or she should be treated,” said Prabhakara Choudary, adjunct professor of psychiatry in the UC Davis Center for Neuroscience, who is co-investigator of the study. “I think this study moves us one small step closer to that goal.”

Choudary also said that the fibroblast growth factor system may one day be useful in developing an accurate tool for diagnosing major depression.

In addition to Jones and Choudary at UC Davis, the study’s authors include: Huda Akil, Simon Evans, Stanley J. Watson, Juan F. Lopez, Robert C. Thompson, J. D. Stead, C. R. Neal and F. Meng from the University of Michigan in Ann Arbor; J. Z. Li and R.M. Myers from Stanford University’s Human Genome Center in Palo Alto, Calif.; and M.P. Vawter, H. Tomita D. M. Walsh, and W. E. Bunney from UC Irvine in Irvine, Calif.