Identification of Molecular Systems Responsible for the Therapeutic Effect of Antidepressant

Summary

Although blockade by antidepressants of monoamine uptake into nerve endings is one of the cornerstones of the monoamine hypothesis of depression, there is a clear discrepancy between the rapid effects of antidepressants in increasing synaptic concentrations of monoamine and the lack of immediate clinical efficiency of antidepressant treatment. Pharmacogenomics, functional genomics and proteomics are powerful tools that can be used to identify genes/ESTs or molecular systems affected by antidepressants. Using a differential cloning strategy, we and other groups have isolated genes that are differentially expressed in the brain after chronic antidepressant treatment. Some of these candidate genes may encode functional molecular systems or pathways induced by chronic antidepressant treatment. Defining the roles of these molecular systems in drug-induced neural plasticity is likely to transform the course of research on the biological basis of depression. Such detailed knowledge will have profound effects on the diagnosis, prevention, and treatment of depression.