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The first survey of the entire human genome for genes that affect the susceptibility of individuals to developing clinical depression has been completed by researchers from the University of Pittsburgh and published this week in the American Journal of Medical Genetics. George S. Zubenko, M.D., Ph.D.,professor of psychiatry and his team have located a number of chromosomal regions that appear to hold the genetic keys to a variety of mental disorders, including major depression and certain addictions. The survey was done in 81 families identified by individuals with recurrent, early-onset, major depressive disorder (RE-MDD), a severe form of depression that runs in families.
The survey revealed 19 loci on the chromosomes where genes reside that appear to influence susceptibility to depressive disorders. The results extended the investigators' previous finding that a small region of chromosome 2q containing the CREB1 gene affects the vulnerability of women to developing depression. And at least some of the 19 depression vulnerability loci appear to work in concert to affect a person's risk of developing depression. Dr. Zubenko pointed out that 'greater scrutiny of the chromosome 2 locus has provided stronger evidence for the role of CREB1 as a risk gene for depressive disorders among women.' In addition, five of the new genetic loci appear to interact with the CREB1 region to affect the risk of developing clinical depression in these families.
It is interesting to note that women are twice as likely as men to develop depression, and genetic differences appear to account for some of that disparity, the researchers report.Sex-specific loci were common and preferentially affected the vulnerability of women to developing unipolar mood disorders. Evidence of at least one male-specific risk locus also was found. The sex-specific effects of particular risk genes for depression may result from the interactions of these genes and their products with sex hormones.
These findings suggest there are important differences in the molecular pathophysiology of mood disorders in men and women, or in the mechanisms that determine resistance to stressful stimuli. They may also help explain the vulnerability of women to depression during times of significant hormonal fluctuation including puberty, menstrual cycling, pregnancy and childbirth and menopause. Conversely, age-related reductions in hormone levels may contribute to a reduced proportion of familial cases of depression among depressions that arise later in life.
For additional reading on the genetics of depressive disorders see the Genetics and Depression Section of Depression Central
For additional information on the Human Genome Project see the Sanger Institute
11:27:21 PM 
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