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Pharmacogenetics of Major Depressive Disorder: Top Genes and Pathways Toward Clinical Applications

  • Genetic Disorders (W Berrettini, Section Editor)
  • Published:
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Abstract

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.

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Chiara Fabbri declares no conflict of interest.

Alessandro Serretti is or has been a consultant/speaker for Abbott, Astra Zeneca, Clinical Data, Boheringer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Lundbeck, Pfizer, Sanofi, and Servier.

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  1. Department of Biomedical and Neuromotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy

    Chiara Fabbri & Alessandro Serretti

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Correspondence to Alessandro Serretti.

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Fabbri, C., Serretti, A. Pharmacogenetics of Major Depressive Disorder: Top Genes and Pathways Toward Clinical Applications. Curr Psychiatry Rep 17, 50 (2015). https://doi.org/10.1007/s11920-015-0594-9

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