Project Summary

Myrna M. Weissman, Ph.D. (Distinguished Investigator 2005) of Columbia University, will study major depression (MDD) by collecting blood samples for DNA from a unique sample of three generations at high and low risk for MDD who she has been following for 20 years. She has already conducted imaging studies which were funded by NIMH, as well as neuropsychological testing and clinical reassessment. She will use NARSAD funds to collect blood samples for DNA and if promising will use these preliminary findings to apply for NIMH funding. Her current findings show the high rate of psychiatric disorders in the grandchildren with two generations of MDD—nearly 60% (average age 12) already have some psychiatric disorder. Like their parents and grandparents, anxiety disorders before puberty are the first sign of psychopathology. As adolescence approaches, mood disorders emerge. Forty percent (40%) of the grandchildren with two antecedent generations of moderate/severe MDD already have a mood disorder. She will first obtain blood from families who will have MRI studies and on those with two generations of MDD, thus allowing her to explore the connection between the rich phenotypes gathered in the course of this study and genes that may play a role in psychopathology. She will investigate the recent findings of linkage between recurrent early onset depression and a region of chromosome 2 near the gene encoding the transcription factor CREB, and will explore a recent finding by another investigator reporting that a functional polymorphism in the promoter region of the serotonin transporter gene moderates the effect of life events on developing depression. The added brain imaging data provides the means to characterize endophenotypes related to MDD that may reflect neurophysiological phenotypic outcomes that may be correlated with the genetic and environmental risk factors. This is a unique dataset which will enable Dr. Weissman to study the genetic architecture of major depression.

Program Area: MOOD DISORDERS\Unipolar Depression

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