A genetic polymorphism within the serotonin transporter gene and response to tryptophan depletion

The tryptophan (TRP) depletion paradigm is a broadly utilized research methodology that safely and effectively has contributed to the improved understanding of the physiological effects of serotonin (5-HT) neurotransmission in a variety of subject populations. Specifically, the TRP depletion paradigm has been proposed as a phenotype for major affective disorders based on its ability to somewhat consistently induce brief and reversible depressive responses in subjects considered at risk for depression. Although several factors, such as treatment history, time in remission, and gender, are thought to affect rates of mood response in some studies, it has been proposed that the presence of functional polymorphisms in certain candidate genes may explain some additional response variability. The need for new phenotypic definitions, such as the mood response during TRP depletion, is supported by the fact that depression is a highly heterogeneous condition, lacks a gold-standard diagnostic biological tool, and is presumed to have a complex polygenic inheritance. This article examines the findings from several studies in which genotyping has been reported in healthy volunteers and remitted depressives. In particular, the relationship between depressive symptom response during TRP depletion and a functional polymorphism of the promoter region of the 5-HT transporter gene will be discussed.