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Introduction: Suicide Attempts (SA) are the main complications of Major Depressive Episodes (MDE) and are difficult to predict. Suicide is associated with the expression of Receptor Tyrosin-Kinase B (TRKB), the receptor of the Brain Derived Neurotrophic Factor (BDNF) involved in MDE. However, the impact of its genetic polymorphisms as predictive factors of SA should be clarified. Our main aim is to assess the association of 8 TRKB genetic polymorphisms and SA in depressed patients., Material and Methods: In 624 patients currently experiencing an MDE in the context of Major Depressive Disorder (MDD) (METADAP study), we assessed the association between 8 TRKB genetic polymorphisms (rs1778933, rs1187352, rs2289658, rs2289657, rs2289656, rs3824519, rs56142442 and rs1439050) and acute (previous month) or past (older than one month) SA. Bonferroni corrections and multivariate analysis adjusted for age, sex, level of education, marital status, Hamilton Depression Rating Scale score and previous MDE were used., Results: The rs2289656 was associated with acute SA (CC = 28.5%, CT = 15.0% and TT = 11.5%, p = 0.0008). However, the other SNPs were not. Patients with the CC genotype had a higher rate of acute SA (28.5%) as compared to T carriers (14.6%) (adjusted OR = 2.2, CI95% [1.4; 3.5], p<0.0001)., Conclusion: The TRKB rs2289656 CC genotype is associated with a 2.2 fold higher risk of acute SA in depressed patients. If this result could be confirmed, this TRKB SNP may be assessed to contribute to the prediction of SA in depressed patients., Competing Interests: Eric Deflesselle, Romain Colle, Laurent Rigal, Céline Verstuyft, Albane Vievard, Severine Martin, Emmanuelle Corruble have no conflict of interest to disclose. Denis Joseph David currently receives investigator-initiated research support from Lundbeck and served as a consultant in the areas of target identification, validation and new compound development to Lundbeck Inc., Roche and Servier. Laurent Becquemont was an investigator for Antisense Therapeutics, Alnylam Pharmaceuticals, Alexion, Actelion, Auris Medical, Gilead Sciences, Ionis Pharmaceuticals, MedDay Pharma, Novartis, PregLem SA, Ultragenix Pharmaceutical. He received consulting fees from Sanofi-Aventis, Pfizer, Kyowa Kirin and Servier, lecture fees from Genzyme, GlaxoSmithKline, Bristol-Myers Squibb, Merck Sharp and Dohme; a close family member works at Sanofi France. This does not alter our adherence to PLOS ONE policies on sharing data and materials

Aim: NTRK2 is the main receptor of the brain derived neurotrophic factor, which is involved in antidepressant efficacy. We assessed the impact of eight NTRK2 SNPs pertaining to response and remission after antidepressant treatment in depressed patients., Patients & Methods: In a naturalistic study, 569 patients with a major depressive episode requiring a new antidepressant treatment were genotyped for eight NTRK2 SNPs (rs1187352, rs1439050, rs1778933 rs2289656, rs2289657, rs2289658, rs3824519, rs56142442) and prospectively assessed for response and remission after 6 months of treatment., Results: No association was shown between the NTRK2 SNPs and response/remission., Conclusion: There is no benefit to assess these eight TRKB SNPs to predict response/remission after antidepressant treatment in depressed patients.

We propose an extensive review of the literature about BDNF/TRKB/P75NTR polymorphisms and their consequences on antidepressant efficacy in depressed patients. Five genome-wide association studies and 30 association studies were included. Twenty seven studies focused on the Val66Met polymorphism (rs6265), the Met allele being associated with a higher antidepressant efficacy only in Asian patients. Other BDNF/TRKB/P75NTR polymorphisms (BDNF: rs7103411, rs7124442, rs908867, rs2049046, rs61888800, rs10501087, rs1491850; TRKB: rs10868223, rs11140778, rs1565445, rs1659412; P75NTR: rs2072446) were reported to be associated with antidepressant efficacy but these results were not replicated. Finally, there are 15 positive studies among 30 studies regarding BDNF/TRKB/P75NTR polymorphisms. The only SNP which benefits of at least three positive studies is the BDNF Val66Met polymorphism (rs6265). Consequently, with a lack of good and consistent studies, the clinical utility of BDNF in treatment selection is far from clear. We propose several recommendations for further studies.