Association Between Polymorphism Of Serotonin Transporter Gene In Major Depression And Therapeutic Response And Adverse Effect With Fluoxetine Treatment

Background: Changes of serotonic system is one of the pathophysiology in depression. As a target of fluoxetine, serotonin transporter(5-HTT) located in presynapse play a important role in serotonic system. Among the various polymorphisms of serotonin transporter gene, most have no effect on function expression and structure of serotonin transporter, but the variable number of tandem repeats(VNTR) in intron 2 have a important impact on function epression of serotonin.Objective: To investigate the association between polymorphism of VNTR in 5-HTT intron 2 and clinical phenotype in major depression and analysis the effect of VNTR polymorphisms on depression. To examine the relationship of 5-HTT intron 2 VNTR polymorphism to antidepressant response and adverse effect of fluoxetine, in order to provide a biological predictive index of individual antidepressant treatment. Methods: 101 patients with major depression diagnosesed by Diagnosis and statistic manual for mental disorder-IV (DSV-IV) were assessed in baseline with Diagnotic interview for genetic studies(DIGS), Hamilton rating scale for depression(HRSD), Zung's Self Depression Scale(SDS), Clinical global impression(CGI), Treatment Emergent Side Effects(TESS) and the genotype of these patients were determined. Patients received a 6 weeks proctocolized treamtment of fluoxetine with a dosage of 20mg per day, and were assessed with HAMD, SDS, TESS at 1,2,4 weeks after baseline. Results: 91(90.1%) patients were found to have the stin2.12/ stin2.12 genotype and 10 (9.9%) patients had stin2.12/ stin2.10 genotype. The age at onset in patients with stin2.12/ stin2.10 genotype were 23.1 ± 7.4, while the stin2.12/ stin2.12 genotype were 35.3 ± 12.5. The difference of age at onset between the two genotypes was statistic signifance(p=0.003). Among the 85 patients who finished the 6 weeks clinical trial, the...