title: Neurotrophin Genes and Antidepressant-Worsening Suicidal Ideation: A Prospective Case-Control Study.
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.
authors.affiliation: 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). geraldine.voegeli@gmail.com.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Voegeli
authors.affiliation: 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).
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ramoz
authors.affiliation: 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).
authors.forename: Tatyana
authors.initials: T
authors.lastname: Shekhtman
authors.affiliation: 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).
authors.forename: Philippe
authors.initials: P
authors.lastname: Courtet
authors.affiliation: 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).
authors.forename: Philip
authors.initials: P
authors.lastname: Gorwood
authors.affiliation: 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).
authors.forename: John R
authors.initials: JR
authors.lastname: Kelsoe
mesh_terms: D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000928:Antidepressive Agents / Q000009:adverse effects*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D016022:Case-Control Studies; D003863:Depression / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D010597:Pharmacogenetics; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D020813:Receptor, trkB / Q000235:genetics*; D012307:Risk Factors; D059020:Suicidal Ideation; D013841:Thiazepines / Q000009:adverse effects*
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D013841:Thiazepines; C050504:tianeptine; C579455:BDNF protein, human; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human
keywords: antidepressant drugs; depression; neutrotrophin; pharmacogenetics; suicide