Association between a serotonin transporter promoter region polymorphism and mood response during tryptophan depletion

This study investigated the relationship between depressive symptom response during tryptophan (TRP) depletion and a functional polymorphism of the promoter region of the serotonin (5-HT) transporter gene (SLC6A4). Forty-three subjects in remission from a major depressive episode who underwent TRP depletion were genotyped. DNA was extracted from blood lymphocytes or from cheek cells. The two common alleles are designated long (/) and short (s). Depressive symptoms were measured with the 25-item Hamilton Depression Rating Scale (HDRS). There was a significant association between the I homozygous genotype and the depressive response to TRP depletion, with a significant main effect of time (F = 8.763, df = 3, 38, P = <0.001), and time x I homozygous allele interaction (F = 3.676, df = 3, 38, P = 0.02). Individuals whose genotype predicted increased 5-HT transporter activity may be more susceptible to depressive changes in response to transient 5-HT perturbations. The use of endophenotypic markers for affective disorders such as the mood response to TRP depletion may facilitate studies of complex genetic traits such as depression by decreasing its heterogeneity.