Neurotrophin Genes and Antidepressant-Worsening Suicidal Ideation: A Prospective Case-Control Study
International Journal of Neuropsychopharmacology, Volume , Issue , 4 July 2016
Géraldine Voegeli, MD, Nicolas Ramoz, PhD, Tatyana Shekhtman, MS, Philippe Courtet, MD, PhD, Philip Gorwood, MD, PhD and John R. Kelsoe, MD Department 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).Correspondence: Geraldine Voegeli, MD, CMME, Sainte-Anne Hospital, Paris, France (firstname.lastname@example.org).
DOI: http://dx.doi.org/10.1093/ijnp/pyw059 pyw059 First published online: 4 July 2016
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.