title: Screening genetic variability at the CNR1 gene in both major depression etiology and clinical response to citalopram treatment.
abstract: BACKGROUND
  The endocannabinoid system has been implicated in the pathogenesis of major depression (MD) as well as in the mediation of antidepressant drug effects.
  
  
  OBJECTIVE
  To analyze CNR1 gene variants in MD and clinical response to citalopram (selective serotonin re-uptake inhibitors [SSRI]).
  
  
  METHODS
  The role of CNR1 gene (rs806368, rs1049353, rs806371, rs806377 and rs1535255) was investigated in 319 outpatients with MD and 150 healthy individuals. A subsample of 155 depressive patients were treated with citalopram and evaluated for response (fourth week) and remission (12th week) by the 21-item Hamilton Depression Rating Scale (HDRS).
  
  
  RESULTS
  We observed a higher frequency of rs806371 G carriers in MD patients with both presence of melancholia (p = 0.018) and psychotic symptoms (p = 0.007) than in controls. Haplotype frequency distributions between MD sample and controls showed a significant difference for Block 1 (rs806368-rs1049353-rs806371) (p = 0.008). This haplotype finding was consistent when we compared controls with MD subsample stratified by melancholia (p = 0.0009) and psychotic symptoms (p = 0.014). The TT homozygous of the rs806368 and rs806371 presented more risk of no Remission than the C carriers (p = 0.008 and 0.012, respectively). Haplotype frequency distributions according to Remission status showed a significant difference for Block 1 (p = 0.032). Also, we observed significant effect of time-sex-genotype interaction for the rs806368, showing that the C carrier men presented a better response to antidepressant treatment throughout the follow-up than TT homozygous men and women group (p = 0.026).
  
  
  CONCLUSIONS
  These results suggest an effect of CNR1 gene in the etiology of MD and clinical response to citalopram.
authors: Unitat d'Antropologia, Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona/Institut de Biomedicina de la Universitat de Barcelona (IBUB), Av. Diagonal, 643 2on pis, 08028 Barcelona, Spain.
authors: Marina
authors: M
authors: Mitjans
authors: Alessandro
authors: A
authors: Serretti
authors: Chiara
authors: C
authors: Fabbri
authors: Cristóbal
authors: C
authors: Gastó
authors: Rosa
authors: R
authors: Catalán
authors: Lourdes
authors: L
authors: Fañanás
authors: Bárbara
authors: B
authors: Arias
mesh_terms: D016022:Case-Control Studies; D015283:Citalopram / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015283:Citalopram; D043884:Receptor, Cannabinoid, CB1; D017367:Selective Serotonin Reuptake Inhibitors; C571130:CNR1 protein, human