Neurotrophin Genes and Antidepressant-Worsening Suicidal Ideation: A Prospective Case-Control Study

Int J Neuropsychopharmacol. 2016 Dec 3;19(11):pyw059. doi: 10.1093/ijnp/pyw059. Print 2016 Nov.

Abstract

Background: Antidepressant-worsening suicidal ideation is a rare but serious phenomenon. This study aimed to test for association between antidepressant-worsening suicidal ideation and polymorphisms of BDNF/NTRK2 neurotrophin pathway genes, known to be involved in depression and suicide.

Methods: This was a case-control study comparing patients with antidepressant-worsening suicidal ideation to patients without. Patients were collected from the GENESE cohort (3771 depressed tianeptine-treated outpatients). Antidepressant-worsening suicidal ideation was defined by an increase of at least 2 points on the Montgomery-Åsberg Depression Rating Scale-item10 during treatment. Controls were matched for age, sex, and baseline Montgomery-Åsberg Depression Rating Scale-item10 score. Thirteen single nucleotide polymorphisms covering 5 BDNF/NTRK2 pathway genes were genotyped.

Results: A total 78 cases and 312 controls were included. Two NTRK2 single nucleotide polymorphisms were associated to antidepressant-worsening suicidal ideation: rs1439050 (P=.01) and rs1867283 (P=.04). Association with rs1439050 remained significant after adjustment for potentially confounding factors, including previous suicide attempts (P<.01).

Conclusions: This naturalistic prospective study is consistent with previous studies on highlighting the potential role of the neurotrophin pathway, and especially of NTRK2, in antidepressant-worsening suicidal ideation.

Keywords: antidepressant drugs; depression; neutrotrophin; pharmacogenetics; suicide.

MeSH terms

  • Adult
  • Aged
  • Ambulatory Care
  • Antidepressive Agents / adverse effects*
  • Brain-Derived Neurotrophic Factor / genetics
  • Case-Control Studies
  • Depression / diagnosis
  • Depression / drug therapy*
  • Depression / genetics
  • Depression / psychology
  • Female
  • Gene Frequency
  • Haplotypes
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Middle Aged
  • Pharmacogenetics
  • Pharmacogenomic Testing
  • Pharmacogenomic Variants*
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Receptor, trkB / genetics*
  • Risk Factors
  • Suicidal Ideation*
  • Thiazepines / adverse effects*

Substances

  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • Thiazepines
  • tianeptine
  • BDNF protein, human
  • Receptor, trkB
  • tropomyosin-related kinase-B, human