Association of the TLR4 gene with depressive symptoms and antidepressant efficacy in major depressive disorder

Neurosci Lett. 2020 Sep 25:736:135292. doi: 10.1016/j.neulet.2020.135292. Epub 2020 Aug 5.

Abstract

At present, the etiology and pathogenesis of major depressive disorder(MDD) are still unclear. Some studies have shown that toll-like receptor 4 may play an important role in MDD. However, little is currently known about the association between TLR4 single gene polymorphisms (SNPs) and depressive symptoms and antidepressant efficacy.The aim of this study is to analyze whether TLR4 SNPs are associated with depressive symptoms and antidepressant efficacy. The study consisted of 438 patients with first-episode depression. We analyzed three TLR4 SNPs (rs1927911, rs11536889, and rs7873784) and obtained the baseline and 6-week scores using the 17-item Hamilton Depression Rating Scale (HAMD17) and its five-factor model. Allelic and genotypic association tests between TLR4 SNPs and HAMD17 total and cluster scores were performed with UNPHASED, while chi-square tests to analyze the association between TLR4 SNPs and response to antidepressants were performed with SPSS. Patients with the rs1927911-GG genotype exhibited higher scores of anxiety (physical symptoms) and anxiety (somatic). Patients with rs1927911-G also exhibited higher anxiety (physical symptoms) and anxiety (somatic) scores. Patients with rs11536889-GG had significantly lower suicide scores and higher psychomotor retardation scores. Patients with rs11536889-G also had significantly lower suicide scores and higher psychomotor retardation scores. Patients with rs7873784-G had higher anxiety (physical symptoms) and anxiety (psychological) scores. There was no significant difference between antidepressant efficacy and TLR4 gene polymorphisms. These findings provide evidence that TLR4 plays an important role in anxiety, suicide, and other symptoms in patients with MDD. No relationship was found between TLR4 gene polymorphisms and antidepressant efficacy in this study. Further research is needed on gene polymorphisms and the expression of TLR4 in patients with MDD.

Keywords: Antidepressant treatment; Major depressive disorder; Single nucleotide polymorphism; Toll-like receptor 4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antidepressive Agents / therapeutic use*
  • Anxiety / genetics
  • Depression / drug therapy
  • Depression / genetics*
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide*
  • Toll-Like Receptor 4 / genetics*
  • Treatment Outcome
  • Young Adult

Substances

  • Antidepressive Agents
  • TLR4 protein, human
  • Toll-Like Receptor 4