title: Association of brain serotonin transporter availability and brain-derived neurotrophic factor in models of serotonin transporter genotypes in healthy subjects.
abstract: The S-allele of functional polymorphisms of the serotonin transporter (SERT) gene has been demonstrated to have lower transcriptional activity compared with the L-allele, which shows low expression of SERT in the brain. However, this finding cannot be consistently replicated in vivo. The aim of this study was to determine the availability of SERT based on SERT genotype. We also examined the relationship between brain-derived neurotrophic factor (BDNF) and the availability of SERT. Sixty-two healthy subjects were recruited. Each subject underwent single-photon emission computed tomography with I-ADAM (I-labeled 2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine) for imaging SERT in the brain. The specific uptake ratio was measured, and venous blood was drawn when the subject underwent single-photon emission computed tomography to evaluate BDNF levels and SERT genotype. All subjects expressed SERT genotypes that were consistent with a biallelic model, and 26 subjects had SERT genotypes that were consistent with a triallelic model. No differences in specific uptake ratio were detected in the midbrain, putamen, caudate, and thalamus based on the SERT genotype using the biallelic and triallelic models. Interestingly, The Pearson correlation coefficient revealed a positive correlation between BDNF and SERT availability. In particular, this relationship was observed in homozygous S-allele expression and a genotype with low functional expression (SaSa/SaLg) in the biallelic and triallelic models of SERT genotypes, respectively. This finding might explain why the SS genotype of SERT did not increase the risk of major depressive disorder in Asian populations and implicate an important role of BDNF in the patients, who has the SS genotype of the SERT gene.
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital & National Yang Ming University, Taipei, Taiwan.
authors.forename: Yuan-Hwa
authors.initials: YH
authors.lastname: Chou
authors.forename: Chih-Ken
authors.initials: CK
authors.lastname: Chen
authors.forename: Shyh-Jen
authors.initials: SJ
authors.lastname: Wang
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Tsai
authors.forename: Jiing-Feng
authors.initials: JF
authors.lastname: Lirng
authors.forename: Ying-Jay
authors.initials: YJ
authors.lastname: Liou
authors.forename: Chun-Lung
authors.initials: CL
authors.lastname: Lin
authors.forename: Kai-Chun
authors.initials: KC
authors.lastname: Yang
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Whai-Chin
authors.initials: WC
authors.lastname: Lo
authors.forename: Mei-Hsiu
authors.initials: MH
authors.lastname: Liao
authors.forename: Chia-Chieh
authors.initials: CC
authors.lastname: Chen
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin