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Neurotrophin Genes and Antidepressant-Worsening Suicidal Ideation: A Prospective Case-Control Study
Géraldine Voegeli1, Nicolas Ramoz2, Tatyana Shekhtman2
1Department of Psychiatry, VA San Diego Healthcare System, La Jolla, CA (Drs Voegeli and Kelsoe); Department of Psychiatry (Dr Kelsoe), and Institute for Genomic Medicine (Ms Shekhtman and Dr Kelsoe), University of California San Diego, La Jolla, CA; INSERM U675, Center for Psychiatry and Neuroscience, Sainte-Anne Hospital, Paris, France (Drs Voegeli, Ramoz, and Gorwood); CMME, Sainte-Anne Hospital, Paris, France (Drs Voegeli and Gorwood); Department of Emergency Psychiatry and Acute Care, CHRU Montpellier, Inserm U1061, University of Montpellier, Montpellier, France (Dr Courtet). geraldine.voegeli@gmail.com.
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.
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