Aossciation Study Of Paroxetine Plasma Concentration And BDNF, GDNF Polymorphisms With Efficacy Of Antidepressant In Hans Major Depressive Disorders

Paroxetine is widely used in clinical treatment of major depressive disorders(MDD) as a representative medicine of selective serotonin uptake inhibitors (SSRIs).However, during the clinical treatment, it was found that patients with MDD with thesame dose of paroxetine may have the different clinical response. Due to MDD isaffected by many factors such as genetic factors and envirtonmental factors, whether thepolymorphism of the related gene effect antidepressant clinical efficacy remains to befurther researched.Previous studies have indicated brain derived neurotrophic factor (BDNF) and glialcells line derived neurotrophic factor (GDNF) are closely related to the atrophy andrepair damaged neurons, and they are both SSRIs downstream signal factors. Therefore,the single nucleotide polymorphisms (SNPs) of BDNF and GDNF are selected toexplore the relationship between them and paroxetine clinical response, in order toguide clinical medication individualization.OBJECTIVE To evaluate the influence of the single nucleotide polymorphism (SNP)rs6265in the brain-derived neurotrophic factor (BDNF) gene,21SNPs of the glial cellline-derived neurotrophic factor (GDNF) gene polymorphism on the efficacy ofparoxetine in patients with major depressive disorder (MDD). METHODS Chinese patients with MDD were selected according to Diagnostic andStatistical Manual of Mental Disorders,4th edition (DSM-IV) criteria. Patients weretreated with paroxetine20mg/day for6weeks. Hamilton Depression Rating Scale(HAMD-17) was evaluated at base-line and at6-week follow-up. Paroxetine plasmaconcentration was detected by high performance liquid chromatography withfluorescence detection (HPLC-FD). Sequenom MassArray system was used forgenotyping.RESULTS At6-week follow-up,219of298patients (73.5%) were responders and79patients (26.5%) were non-responders to paroxetine treatment. There was a significantcorrelation between paroxetine plasma concentration and antidepressant effect.Eliminated the influence of paroxetine plasma concentration, to BDNF, a significantlyhigher frequency of patients with G allele of rs6265was found in non-responders thanin responders (p <0.001), grouped the patients by gender, data results displayed that thesignificant difference only existed in female (p=0.019). To GDNF,2SNPs (rs2973049,rs2216711) were found has significantly difference between responders andnon-responders involving21SNPs. Patients with A allele of rs2973049has a higherfrequency in non-responders than in responders (p=0.005), and with no genderdifference. Patients with T allele of rs2216711has a higher frequency innon-responders than in responders (p=0.006), and the significant difference onlyexisted in female (p <0.001).CONCLUSION Paroxetine plasma concentration is significantly correlated to theantidepressant effect in MDD patients and the lower threshold level of paroxtine is50.31ng/ml. The SNP rs6265in the BDNF gene and rs2216711, rs2973049in theGDNF gene may influence the clinical efficacy of paroxetine in patients with MDD. The analysis of the two neurotrophic factor genotypes may be useful in identifyingpatients with MDD who have different clinical responses to paroxetine.