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

  • Author(s): Voegeli, Géraldine;
  • Ramoz, Nicolas;
  • Shekhtman, Tatyana;
  • Courtet, Philippe;
  • Gorwood, Philip;
  • Kelsoe, John R
  • et al.
Abstract

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. 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. 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). 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.

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