| ObjectiveFirst,the methylation level of CpG site in exon I region of BDNF(BDNF)gene was detected by Quantitative Methylation-Specific PCR(QMSP)technique in the control group and healthy control group.To investigate the methylation of BDNF gene in case group and healthy control group,we detected whether DNA methylation in exon I region of BDNF was involved in the development of depression.At the same time,the Hamilton Depression Scale(HAMD)and the Life Event Scale(LES)were used to evaluate the factors such as depressive symptoms,stressful life events and suicidal ideation in the case group.The relationship between methylation and the above factors was explored to further explore the role of methylation in the development and progression of depression.Secondly,the methylation level of BDNF gene in the case group was compared with that of sertraline monotherapy for 4 weeks,and the role of BDNF gene related methylation in the treatment of sertraline antidepressant therapy was explored.The baseline methylation level of the case group was compared with that of sertraline before and after treatment,and the level of BDNF methylation at baseline was used as an index to judge the efficacy.In addition,the relationship between BDNF gene methylation and BDNF concentration was determined by Enzyme-linked Immunosorbent Assay(Elisa)in the baseline group and peripheral blood BDNF concentration after 4 weeks of sertraline treatment.The polymorphism of BDNF gene was analyzed by MassARRAY SNP genotyping technique to study the possible interaction between BDNF gene polymorphism and methylation.Finally,it is important to understand whether the BDNF gene-related methylation modification is involved in the pathophysiological process of depression and whether its methylation level can be used as an epigenetic marker for disease diagnosis and antidepressant therapeutic efficacy evaluation.Method1.According to the standard of admission,42 patients with depression who were hospitalized and hospitalized in a hospital in Ningbo from December 2015 to July 2016 were selected as the case group.32 patients who were matched with the case group were selected for sex and age Volunteers as control group.2.At the baseline,5 ml of peripheral venous blood was collected from each group and the upper plasma and lower blood cell components were separated by centrifugation.The plasma of the case group was used for the determination of BDNF concentration.All the blood cell samples were extracted by genomic DNA for SNP and methylation quantitative detection.After 4 weeks of treatment with sertraline monotherapy,5 ml of peripheral blood was collected from all the cases,and the plasma BDNF concentration and gene polymorphism and methylation were repeated.3.The Hamilton Depression Scale(HAMD),and the Life Event Scale(LES)assessment,as well as EEG and ECG monitoring,were performed twice a week after baseline treatment and sertraline treatment.All assessment and monitoring were performed in the patient’s calm state.4.In this study,SPSS18.0 software was used for data analysis.The correlation between the data of the normal distribution data was analyzed by t test,single factor analysis and so on.The correlation test was performed by rank correlation test using the rank correlation test.All data are expressed as mean ± standard deviation.Results1.There was no significant difference in plasma BDNF between the baseline group and the serotonin group after 4 weeks of treatment.There was no significant difference in plasma BDNF between the two groups before and after treatment with sex and genotype.2.The correlation between plasma BDNF and BDNF methylation level was found at baseline,and no correlation was found between the two groups.There was no correlation between BDNF concentration and methylation level in the case group after further analysis of genotype stratification.3.The methylation level of BDNF gene in the healthy control group and the case group was statistically significant,and the methylation of the BDNF gene was lower than that of the healthy control group.According to sex further stratification analysis,the difference still exists statistically significant.4.There was a positive correlation between the methylation level of BDNF gene and HAMD in the case group at baseline,and the results showed that there was positive correlation between day and night change and block factor and methylation.There was no correlation between HAMD total score,anxiety or somatization,weight,cognitive impairment,sleep disturbance,despair factor and methylation level.After further stratification of sex,it was found that there was no significant correlation between HAMD total score,day and night,and block factor and methylation.At the same time,the average methylation level of BDNF gene in the case group was correlated with the score of life events(LES).The results showed that the average methylation level was correlated with the total score of LES and the scores of each factor.5.There was no significant difference in the methylation level of BDNF gene between the baseline group and sertraline group after 4 weeks of treatment.Further analysis by sex and genotype stratification analysis,the difference was still not statistically significant.There was no correlation between the methylation level of BDNF gene and the difference of HAMD score before and after the treatment with sertraline.6.There was no significant difference in BDNF gene methylation between the different family history and suicidal ideation.The methylation level of BDNF gene in the case group was correlated with the age of the case group,the time of administration and the level of cysteine.The results showed that the level of BDNF methylation was not correlated with the above factors.After comparison,the baseline level of BDNF methylation was not found to be related to the above factors.Conclusion:1.4 weeks of sertraline treatment did not change the peripheral blood BDNF concentration.BDNF concentration levels may not be an objective indicator of the efficacy of sertraline drugs.2.BDNF gene exon I region CpG methylation level may not affect the plasma BDNF concentration,that is,the detection site of methylation may not participate in the regulation of BDNF concentration.3.BDNF gene exon I region CpG site methylation may be involved in the pathophysiology of depression.,the methylation level may not be used as a diagnostic indicator of depression.4.There was a positive correlation between the methylation level of CpG site in the exon I region of BDNF gene and the HAMD total score and its factor scores including day and night changes and blockages,that is,the higher the level of BDNF methylation,the higher the total score of HAMD,The more obvious the block.Further analysis showed that gender and age factors may be involved in the above regulation.5.Antidepressant sertraline does not alter the methylation level of the CpG site in the exon I region of the peripheral blood BDNF gene.The methylation of the relevant site may not be the mechanism of sertraline antidepressant therapy.And the baseline level of methylation can not be used as a predictor of subsequent drug treatment.6.BDNF gene exon I region CpG site methylation modification is not the pathophysiological mechanism of suicidal ideation.Age,sex,medication time,cysteine and other factors do not affect the relevant methylation process. |
PDF Full Text Request