The Relationship Of Brain Derived Neurotrophic Factor And Its Polymorphisms With Depressive Disorder

Objective1.Identify the interrelated relationship among BNDF levels in serum,gender,age of onset,symptom and response to paroxetine in a Chinese population with depressive disorder(DD)。2.Identify the relationship between the G196A polymorphism in the BNDF gene and gender,age of onset,severity,symptomthe and response to paroxetine in a Chinese population with depressive disorder(DD)。3.Identify the relationship between the G196A polymorphism in the BNDF gene and BNDF levels in serum in a Chinese population with or without depressive disorder (DD)。Methods1.Object depressive group:88 cases,were sampled from outpatient of Department of Neurology,Qilu Hospital of Shandong University,and all participated in voluntary.Control group:165 cases,were sampled from students of Shandong University,Employee of Qilu Hospital and examinee of Medical examination center,Qilu Hospital.According to age,all subjects were divided into young group(＜50 years)and elder group(≥50).According to the change of HAMD scales before and after treatment,all patients were divided into responders(Rp,≥50%)and nonresponders(Non-Rp,＜50%). 2.Scale measure Basic information questionnaire was administrated to all subjects. HAMD was examed at the baseline in the control group,and was examed the baseline and 4 weeks after treatment in the control group.3.Blood measure Blood samples were collected into CTAD Vacutainer EDTA tubes (Becton Dickinson,USA),and genomic DNA was isolated using Ready Amp^TM Genomic DNA Purification System kits(Promega)or MagExtractor-Genome-NPK100 kit(TOYOBO).BDNF genetype for the polymerphisms of G196A and C270T were performed by PCR amplification of genomic DNA,followed by restriction enzyme digestion.The Products were analysed by the method of agarose or PAGE electrophoresis,some PCR products were sequenced by Biosystem biology technology limited company.The serum BDNF levels assayed with ELISA Kit(Boster biology technology limited company,Wuhan)。4.Statistics Association analysis was performed by using SPSS 11.5 software. Measurement datas were shown in the form of mean±standard deviation((?)±S) and its comparison among groups were conducted by the way of one-way analysis of variance(one-way ANOVA)or t-test for independent samples. Enumeration datas were shown in the form of rate and its comparison among groups were conducted by the way of chi-sequare test(x² test).The comparative risk rate of factors was demonstrated by odds ratio(OR)accompanied by 95% confidence interval(CI).P＜0.05 was considered to be significant.Results1.Serum BDNF levels were significantly lower in depressive disorder patients than normal controls(depressive groups 15.801±3.860,control group 25.486±5.368,t=16.513,P=0.000).Treatment had an effect on the normalization of serum BDNF levels(pretherapy 15.801±3.860,post-treatment 21.981±3.386, t=20.226,P=0.000).positively relevant2.The total score of HAMD was negative correlation to serum BDNF levels (r=-0.745,P=0.000).3.No significant difference for BDNF gene G196A or C270T polymorphism between patients and controls groups,but there were ethnic difference.Depressed subjects of elder subgroup were more likely to be A196 allele carriers than comparison subjects(x²=4.876,P=0.027,OR=3.333,95%CI=1.108-10.027).4.There were no positively relevant between genetype or genetic allele carrier of G196A gene polymorphism and BDNF levels in serum.5.No significant differences were found for age,BDNF levels in serum or its changes,score of HAMD or responds to paroxetine treatment between male and female depressive disorder groups.6.No significant differences were found for sex,age,BDNF levels in serum or its changes,score of HAMD or responds to paroxetine treatment between young and elder depressive disorder groups.7.No significant differences were found for sex,age,BDNF levels in serum or its changes,score of HAMD between response and non-response depressive disorder groups;but post-treatment serum BDNF levels of response group is higher than non-response group,and the changes of serum BDNF levels is more significant.8.The G196A polymorphism of BDNF is associated with paroxetine efficacy in depressive disorder,with A-allele carriers responding better to paroxetine treatment(x²=5.623,P=0.018,OR=3.133,95%CI=1.195-8.214).No significant differences were found for patients' gender,age of onset,symptoms and severity among different genetypes.Conclusions:1.Serum BDNF level is related to HAMD in depressive disorder and that BDNF level may be a biological marker of depressive disorder.2.Depressed subjects of elder subgroup were more likely to be A196 allele carriers than were comparison subjects 3.The G196A polymorphism of BDNF is associated with paroxetine efficacy in depressive disorder,with A-allele carriers responding better to paroxetine treatment.