title: Genetic variability in the endocannabinoid system and 12-week clinical response to citalopram treatment: the role of the CNR1, CNR2 and FAAH genes.
abstract: First line treatment of major depression is based on selective serotonin re-uptake inhibitors (SSRIs) that enhance serotonergic neurotransmission by blocking the serotonin transporter. However, clinical response is a complex phenomenon in which other systems such as the endocannabinoid system could be involved. Given the evidence for the role of the endocannabinoid system in the pathogenesis of depression as well as in the mediation of antidepressant drug effects, the aim of this study was to analyze genetic variability in the endocannabinoid system genes (CNR1, CNR2 and FAAH genes) and their role in clinical response (at week 4) and remission (at week 12) in SSRI (citalopram) treatment in a sample of 154 depressive outpatients, all of Spanish origin. All patients were treated with citalopram and followed over 12 weeks. Severity of depressive symptomatology was evaluated by means of the 21-item Hamilton Depression Rating Score (HDRS). No differences were found in any of the genotype distributions according to response or remission. The longitudinal study showed that (i) the CNR1 rs1049353-GG genotype conferred a better response to citalopram treatment in the subgroup of male patients and (ii) G allele carriers (CNR2 rs2501431) presented higher HDRS scores in the follow-up than AA homozygous allele carriers. Our results seem to suggest the involvement of CNR1 and CNR2 genes in clinical responses to citalopram treatment.
authors: Unitat d'Antropologia, Universitat de Barcelona, Barcelona, Spain.
authors: Marina
authors: M
authors: Mitjans
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: D000328:Adult; D000581:Amidohydrolases / Q000235:genetics* / Q000378:metabolism; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D015283:Citalopram / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics* / Q000378:metabolism; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013030:Spain; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D017367:Selective Serotonin Reuptake Inhibitors; D000099252:Fatty Acid Amide Hydrolases; C571130:CNR1 protein, human