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A sex-specific gene for depression

Depression is the second-leading cause of disability worldwide, affecting nearly 10% of the population. According to George S. Zubenko, M.D., Ph.D., professor of psychiatry at the University of Pittsburgh School of Medicine and adjunct professor of biology at Carnegie Mellon University, women are twice as likely as men to develop depression, and genetic differences appear to account for some of that disparity.

These latest results build on research published by Dr. Zubenko and his team in October of 2002 that identified a small region of chromosome 2 equal to 0.01 percent of the human genome as the potential hiding place for a susceptibility gene for depression in women. "These findings confirm our earlier research suggesting the existence of susceptibility genes that have sex-limited effects on the vulnerability of women to developing severe depression," said Dr. Zubenko. "Over 80% of women in our study who inherited a particular variant of CREB1 developed depressive disorders, while a second version of this gene appeared to have protective effects."

CREB1 is a gene that encodes a regulatory protein called CREB that orchestrates the expression of large numbers of other genes that play important roles in the brain and the rest of the body as well. The widespread importance of CREB as a genetic regulator throughout the body suggests that the newly identified CREB1 variants may influence the development of additional psychiatric disorders related to depression, such as alcohol and other substance use disorders, as well as medical conditions that are associated with depression.

The identification of CREB1 leads Dr. Zubenko's team to believe that genes for other components of cell signaling pathways that operate through CREB may be involved in mood disorders. Further study along those lines could lead to the identification of additional susceptibility genes for mood disorders and shed light on important differences in the pathophysiology o
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Contact: Aimee Midei
molecularpsychiatry@mednet.ucla.edu
310-206-6739
Molecular Psychiatry
14-Jul-2003


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