title: Association study of CREB1 polymorphisms and suicidality in MDD: results from a European multicenter study on treatment resistant depression.
abstract: OBJECTIVE
  Mood disorders are present in more than 90% of suicides, and a genetic vulnerability to suicidality is well established. Numerous lines of evidence relate the transcription factor Cyclic adenosine monophosphate Response Element Binding protein (CREB1) to suicide, and to the aetiology of major depressive disorder (MDD). Our aim was to test for association between CREB1 single nucleotide polymorphisms (SNPs) and both suicide risk (SR) and a personal history of suicide attempt (SA) in MDD patients.
  
  
  METHODS
  A sample of 250 MDD patients collected in the context of a European multicenter resistant depression study and treated with antidepressants over a period of at least 4 weeks were genotyped for five CREB1 SNPs (rs2709376, rs2253206, rs7569963, rs7594560, and rs4675690). To assess suicidality, the Mini International Neuropsychiatric Interview (MINI) and the Hamilton Rating Scale for Depression (HAM-D) were applied.
  
  
  RESULTS
  Neither single-marker nor haplotypic association were found between SR and/or a personal history of SA with any of the investigated SNPs after multiple testing correction. For females, an association between rs2709376 and a personal history of SA was found (p = 0.016), however not resisting multiple testing correction.
  
  
  CONCLUSIONS
  Although we found significant CREB1 single marker association with a personal history of SA in female MDD patients, this finding could not be confirmed in haplotypic analyses after multiple testing correction. Larger well-defined cohorts are required to confirm or refute a possible association of CREB1 and SA in female MDD patients.
authors: 1Department of Psychiatry and Psychotherapy, Medical University Vienna, Austria.
authors: Laura
authors: L
authors: Carlberg
authors: Alexandra
authors: A
authors: Schosser
authors: Raffaella
authors: R
authors: Calati
authors: Alessandro
authors: A
authors: Serretti
authors: Isabelle
authors: I
authors: Massat
authors: Konstantinos
authors: K
authors: Papageorgiou
authors: Neslihan A
authors: NA
authors: Kocabas
authors: Julien
authors: J
authors: Mendlewicz
authors: Joseph
authors: J
authors: Zohar
authors: Stuart A
authors: SA
authors: Montgomery
authors: Daniel
authors: D
authors: Souery
authors: Siegfried
authors: S
authors: Kasper
mesh_terms: D000328:Adult; D000368:Aged; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics* / Q000523:psychology*; D005060:Europe / Q000453:epidemiology; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012306:Risk; D012727:Sex Characteristics; D013406:Suicide, Attempted / Q000523:psychology* / Q000706:statistics & numerical data
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein
keywords: CREB1; depression; genetic association; suicide