Fabbri Chiara, Serretti Alessandro
Department of Biomedical and Neuromotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy,
Curr Psychiatry Rep. 2015 Jul;17(7):50. doi: 10.1007/s11920-015-0594-9.
The pharmacogenetics of antidepressants has been not only a challenging but also frustrating research field since its birth in the 1990s. Indeed, great expectations followed the first evidence of familiar aggregation of antidepressant response. Despite the progress from candidate gene studies to genome-wide association studies (GWAS), results fell out the expectations and they were often inconsistent. Anyway, the cumulative evidence supports the involvement of some genes and molecular pathways in antidepressant efficacy. The best single genes are SLC6A4, HTR2A, BDNF, GNB3, FKBP5, ABCB1, and cytochrome P450 genes (CYP2D6 and CYP2C19). Molecular pathways involved in inflammation and neuroplasticity show the greatest support. The first studies evaluating benefits of genotype-guided antidepressant treatments provided encouraging results and confirmed the relevance of SLC6A4, HTR2A, ABCB1, and cytochrome P450 genes. Further progress in genotyping and data analysis would allow to move forward and complete the understanding of antidepressant pharmacogenetics and its translation into clinical applications.
自20世纪90年代诞生以来，抗抑郁药的药物遗传学一直是一个既具有挑战性又令人沮丧的研究领域。的确，抗抑郁反应家族聚集性的首个证据出现后带来了巨大期望。尽管从候选基因研究发展到全基因组关联研究（GWAS）取得了进展，但结果却不尽如人意，而且常常不一致。无论如何，累积证据支持一些基因和分子途径参与抗抑郁药疗效。最具代表性的单个基因是SLC6A4、HTR2A、BDNF、GNB3、FKBP5、ABCB1和细胞色素P450基因（CYP2D6和CYP2C19）。涉及炎症和神经可塑性的分子途径得到了最有力的支持。首批评估基因型指导的抗抑郁治疗益处的研究取得了令人鼓舞的结果，并证实了SLC6A4、HTR2A、ABCB1和细胞色素P450基因的相关性。基因分型和数据分析的进一步进展将有助于推进并完善对抗抑郁药药物遗传学的理解及其在临床应用中的转化。
