Genetic variation in IL-1β, IL-2, IL-6, TSPO and BDNF and response to duloxetine or placebo treatment in major depressive disorder

Pharmacogenomics. 2015 Nov;16(17):1919-29. doi: 10.2217/pgs.15.136. Epub 2015 Nov 10.

Abstract

Aim: This study investigated polymorphisms of five inflammatory-related genes for association with duloxetine and placebo response in patients with major depression.

Patients & methods: Twenty SNPs in IL-1β, IL-2, IL-6, TSPO and BDNF were genotyped in major depressive disorder patients treated with either duloxetine (n = 215) or placebo (n = 235) for up to 8 weeks. Treatment response was measured with the Montgomery-Åsberg Depression Rating Scale.

Results: IL-6 variants rs2066992 and rs10242595 were nominally associated with response to duloxetine (p = 0.047 and p = 0.028, respectively). Notably, the variant rs2066992 was also associated with placebo response (p = 0.026). However, none of our results remained significant after correction for multiple testing.

Conclusion: Our findings tentatively suggest that IL-6 variants play a role in duloxetine and placebo response, which warrants further investigation.

Keywords: BDNF; IL-6; TSPO; cytokines; depression; duloxetine; inflammation; placebo; treatment response.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use
  • Brain-Derived Neurotrophic Factor / genetics*
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / genetics*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Duloxetine Hydrochloride / therapeutic use*
  • Female
  • Genetic Variation / genetics
  • Humans
  • Interleukin-1beta / genetics*
  • Interleukin-2 / genetics*
  • Interleukin-6 / genetics*
  • Male
  • Middle Aged
  • Receptors, GABA / genetics*
  • Treatment Outcome

Substances

  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-2
  • Interleukin-6
  • Receptors, GABA
  • TSPO protein, human
  • BDNF protein, human
  • Duloxetine Hydrochloride