The role of BDNF exon I region methylation in the treatment of depression with sertraline and its clinical diagnostic value

J Clin Lab Anal. 2021 Nov;35(11):e23993. doi: 10.1002/jcla.23993. Epub 2021 Sep 15.

Abstract

Background: Brain-derived neurotrophic factor (BDNF) is considered to be one of the best candidate genes for depression. However, whether sertraline treatment affects the methylation level of this gene remains unknown.

Methods: Fifty-three patients with depression and 51 healthy controls were included in the study. The methylation level of BDNF exon I was determined in blood samples from these subjects. The Hamilton Depression Scale was used to evaluate the depression status of patients. Single nucleotide polymorphism detection was used for genotyping, and a receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the methylation level of this locus in patients with depression.

Results: There was a significant difference in the methylation level of BDNF exon I between the control and depression groups. No effect of sertraline monotherapy on BDNF methylation was found in subjects with depression. Moreover, no interaction was found between BDNF genotype and the per cent methylation of BDNF exon I. However, methylation at this site was positively correlated with diurnal variation and retardation scores. Blood homocysteine concentrations were significantly reduced by sertraline treatment. No influence of genotype on serum BDNF concentration was found in subjects with depression. The ROC curve showed that methylation of BDNF exon I may be used to distinguish patients from healthy people, to a certain extent.

Conclusion: Methylation of BDNF exon I may be used as a biomarker of depression and may be a therapeutic target for previously untreated depression.

Keywords: 5-hydroxytryptamine; BDNF; depression; gene methylation; sertraline.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / therapeutic use*
  • Biomarkers / blood
  • Brain-Derived Neurotrophic Factor* / blood
  • Brain-Derived Neurotrophic Factor* / chemistry
  • Brain-Derived Neurotrophic Factor* / genetics
  • Case-Control Studies
  • DNA Methylation / genetics*
  • Depression* / drug therapy
  • Depression* / epidemiology
  • Depression* / genetics
  • Exons / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • ROC Curve
  • Sertraline / therapeutic use*
  • Young Adult

Substances

  • Antidepressive Agents
  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human
  • Sertraline