Promoter prognostication: the serotonin transporter gene and antidepressant response

Abstract

The serotonin transporter has long been a focus of studies of mood disorders because of its role as a site of antidepressants. The recent cloning of the gene and identification of a functional polymorphism have fueled a new round of intriguing results regarding the gene's role in illness. These data have suggested that a low transcriptional activity allele predisposes to mood disorder. A report by Smeraldi et al in this issue further indicates that individuals with this low activity allele are more likely to have treatment refractory illness and to respond to augmentation with the 5-HT_1A antagonist, pindolol. Together these data suggest that the low activity allele may predispose to a form of illness in which the serotonin system is inhibited through activation of somatodendritic 5-HT_1A receptors. It also provides an exciting glimpse into possible future applications of pharmacogenetics.