Unitat d'Antropologia, Departament de Biologia Animal, Facultat de Biologia and Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain.
Neuropsychobiology. 2013;67(1):41-7. doi: 10.1159/000343388. Epub 2012 Dec 4.
Serotonergic genes have been widely investigated regarding antidepressant response in major depressive disorder (MDD) but results are still not univocal.
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.
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.
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.
在重度抑郁症（MDD）中，血清素能基因与抗抑郁反应的相关性已得到广泛研究，但结果仍不明确。
159 名接受西酞普兰治疗的 MDD 患者进行基因分型，并在 12 周的随访期间，在开始时和每 4 周进行 21 项汉密尔顿抑郁评定量表（HAMD）评估。对四个与治疗结果相关的血清素相关遗传变异进行了检测：色氨酸羟化酶 1（TPH1）rs1800532、单胺氧化酶 A µVNTR、5-羟色胺 2A 受体 rs6311 和 5-羟色胺 2C 受体 rs6318。在整个样本和通常具有更高临床严重程度的抑郁亚型（精神病性和忧郁性 MDD）中，测试了这些多态性的作用。
四个多态性对反应、缓解和症状改善均无影响。然而，rs1800532 发现对 MDD 亚型的结果有影响：A 等位基因预测精神病性（F₆,₃₇₈ = 2.90；p = 0.009）和忧郁性（F₆,₃₈₁ = 2.86；p = 0.0097）MDD 的反应更差。
TPH1 rs1800532 的 A 等位基因可能仅与西酞普兰在忧郁性和精神病性 MDD 中的疗效相关。这些结果表明，结合特定的临床特征研究遗传变异的影响是有用的。
