Serotonin-transporter-linked promoter region polymorphism and serotonin transporter binding in drug-naïve patients with major depression: SERT polymorphism and imaging

Aims: Both the serotonin transporter and its genetic regulation by the serotonin-transporter-linked polymorphic region have a role in the pathophysiology of depression. Most of the previous studies have found no influence of serotonin-transporter-linked polymorphic region allelic variation on serotonin transporter binding in healthy controls or patients with major depression. Due to the inconsistency of the previous findings, we compared single photon emission computed tomography imaging with the serotonin-transporter-linked polymorphic region genotype in patients with major depressive disorder. Methods: A total of 23 drug-naive patients with major depressive disorder were genotyped and brain imaged with ([123I])nor-beta-CIT single photon emission computed tomography. The severity of depression was evaluated with the 17-item Hamilton depression rating scale. Results: Depressed patients homozygous for the short allele had lower ([123I])nor-beta-CIT binding in the medial prefrontal cortex, but not in the midbrain, compared with the other genotypes. Conclusion: The decreased medial prefrontal cortical serotonin transporter binding in the patients homozygous for the short allele may be linked to altered function of the serotonin-transporter-linked polymorphic region gene expressed in these patients, especially in the medial prefrontal cortex.