TPH1, MAOA, serotonin receptor 2A and 2C genes in citalopram response: possible effect in melancholic and psychotic depression.

BACKGROUND: Serotonergic genes have been widely investigated regarding antidepressant response in major depressive disorder (MDD) but results are still not univocal. METHODS: 159 MDD patients treated with citalopram were genotyped and evaluated by the 21-item Hamilton Depression Rating Scale at the beginning and every 4 weeks during the 12-week follow-up. Four serotonin-related genetic variants were tested for association with treatment outcome: tryptophane hydroxylase 1 (TPH1) rs1800532, monoamine oxidase A µVNTR, serotonin 2A receptor rs6311 and serotonin 2C receptor rs6318. The effect of these polymorphisms was tested both in the whole sample and in depressive subtypes with usually higher clinical severity: psychotic and melancholic MDD. RESULTS: No effect on response, remission and symptom improvement was found for the four polymorphisms. However, rs1800532 was found to affect the outcome depending on the MDD subtype: the A allele predicted worse response both in MDD with psychotic (F₆,₃₇₈ = 2.90; p = 0.009) and melancholic (F₆,₃₈₁ = 2.86; p = 0.0097) features. CONCLUSIONS: The A allele at TPH1 rs1800532 may be associated with citalopram efficacy only in melancholic and psychotic MDD. These results suggest the usefulness of investigating the effect of genetic variants in conjunction with specific clinical features.