New drug targets in the signaling pathways activated by antidepressants

Studies of twins, genetic linkage and association support the existence of a genetic component to the susceptibility to depression. Biochemical parameters that change in depressive patients are also observed in their relatives. This indicates that genetic factors control these physiological changes and the susceptibility to depression. The study of the mechanisms by which different genetic factors affect the organism's response to drugs can identify better diagnostic tools as well as drug targets. Pharmacogenomics can, therefore, help to find the most efficacious treatment for patients with specific genetic profiles. However, the genetic factors that determine the susceptibility to depression and the different responses to antidepressant treatment are largely unknown. Pharmacogenetic studies have used three different categories of genes to search for associations with the outcome of drug treatments. These gene categories are drug-metabolizing enzymes, known drug targets and known susceptibility genes. The present review will explore the different signal transduction pathways involved in antidepressant action and their possible use in psychopharmacogenomics and drug discovery. (c) 2005 Elsevier Inc. All rights reserved.