Polymorphism Of Serotonin Transporter Gene Influences Core Symptoms And Treatment Response With Fluoxetine For Major Depression

【Background】: The phenotypes differ among depression patients. Core symptoms (including depressive symptom and retard symptom) and accompanied symptoms (including sleep disorders, anxiety symptoms and somatic symptoms) may vary clinically, as well as pharmaceutical treatment response. Major depression is a heredity characteristic brain dysfunction disorder. Single nucleotide polymorphism (SNP) provides important gene clue in the study of pathogenesis and diagnosis of the disease. Changes of serotonin system are known as important pathophysiology in depression. As the key role in pathogenesis and the target of selective serotonin reuptake inhibitor, serotonin transporter gene becomes a candidate gene for major depression.【Objective】: To explore the relationship between 5HTT inton 13 SNP C/T (db SNP rs 2054847) and phenotype, and then evaluated association of therapeutic respond and 5HTT genotype. At the molecular organism's level we investigated whether genetic factor can modify the phenotype and the therapeutic effect. Offer objective evidence for individualized treatment and reference for development new type antidepressive agents.【Methods】Part A: 761 patients according to Diagnosis and statistic manual for mental disorder-Ⅳ(DSM-Ⅳ) criterion diagnosed with major depressive disorder were included. The whole patients' age≥18 year, HAMD-17 scores≥16, without history of mania or hypomania and dysthymic disorder in the baseline. We used DIGS (Diagnostic interview for genetic studies), HAMD-17 and CGI to evaluate the patients' condition. Apply with the Taqman SNP technology to identification genotype. Part B: we prescribed PROZAC (fluoxetine) 20mg/d (fixed dosage) for the patients, and then followed up and evaluated with HAMD scales on 8d, 15d, 29d and 43d respectively.【results】: In the baseline, 761 cases were included in the study. Female patients(420 cases) were male patients(341cases) 1.23 times, average age was 34.2years. average HAMD scores were 22.62. The single episode patients were 2 times than recurrent patients.56% of the patients (425 cases) had genotype. Genotype frequency were TT:65.4%, CT:31.8% and CC2.8% respectably. Allele frequency T: 81.3%, C: 18.7%, according with Hardy-Weinberg equilibrium. In the base line, the patients with TT genotype have higher HAMD scores and report more life events in one year than CT and CC genotype. The patients with TT genotype had higher scores in core symptom factor, retard factor and Maier factor but not in sleep and anxious symptoms, than other genotypes. All patients with fluoxetine 20 mg/d (fixed dosages) treatment. At the end of study, TT patients have a higher tendency in reduction of HAMD scores and responsive ratio than other genotypes. TT patients' remitters (48.3%) were 1.68 fold than CC and CT genotype (39.3%). TT patients' core symptom improvement come up early.【conclusions】In baseline, the severity of patients with depression was modified by 5HTT genotype, especially on core symptoms, but not on sleep and anxious symptoms. This result supports 5HTT receptor had internal association with pathogenesis of depression. Treatment response of SSRI agent was modified by genotype, focusing on core symptom. That accord with the mechanism of drug action.