title: Clinical and genetic correlates of suicidal ideation during antidepressant treatment in a depressed outpatient sample.
abstract: OBJECTIVE
  This study investigated clinical and genetic predictors of increasing suicidal ideation during antidepressant treatment.
  
  
  METHODS
  A total of 131 depressed outpatients were allocated to four antidepressants (paroxetine, venlafaxine, clomipramine or nefazodone) in a sequential step procedure until remission. Suicidality was assessed using the 10th item of the Montgomery-Asberg Depression Rating Scale (MADRS). A total of 11 candidate genes involved in different mechanisms of antidepressant action were selected for association with increasing suicidality.
  
  
  RESULTS
  Increasing suicidality correlated with depression severity and higher antidepressant blood levels. Risk of increasing suicidal ideation was higher in subjects taking antidepressants other than paroxetine (odds ratio: 1.11). The strongest genetic predictor was found to be rs1360780 within the FKBP5 gene (p = 2.9 × 10(-5)), followed by 2677G>T in the ABCB1 gene. The rs130058 SNP within the 5-HTR1B gene demonstrated a differential association with increasing suicidal ideation depending on antidepressant type.
  
  
  CONCLUSIONS
  Increasing suicidal ideation might be an adverse effect of antidepressants. The involvement of FKBP5 indicates that dysregulation of the hypothalamic-pituitary-adrenal axis is involved in treatment increasing suicidal ideation.
authors: Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland. nader.perroud@hcuge.ch
authors: Nader
authors: N
authors: Perroud
authors: Guido
authors: G
authors: Bondolfi
authors: Rudolf
authors: R
authors: Uher
authors: Marianne
authors: M
authors: Gex-Fabry
authors: Jean-Michel
authors: JM
authors: Aubry
authors: Gilles
authors: G
authors: Bertschy
authors: Alain
authors: A
authors: Malafosse
authors: Markus
authors: M
authors: Kosel
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D002997:Clomipramine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D003511:Cyclohexanols / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D010879:Piperazines; D020641:Polymorphism, Single Nucleotide; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics; D012720:Severity of Illness Index; D059020:Suicidal Ideation; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D014230:Triazoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000928:Antidepressive Agents; D002997:Clomipramine; D003511:Cyclohexanols; D017374:Paroxetine; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D022021:Tacrolimus Binding Proteins; D014230:Triazoles; D000069470:Venlafaxine Hydrochloride; D000099159:Tacrolimus Binding Protein 5; C513055:ABCB1 protein, human; C470302:HTR1B protein, human; C051752:nefazodone