title: Pharmacogenetics of major depressive disorder: top genes and pathways toward clinical applications.
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.
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy, chiara.fabbri@yahoo.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fabbri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects / Q000235:genetics; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000235:genetics; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D010597:Pharmacogenetics; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000928:Antidepressive Agents; D044348:Receptors, Serotonin, 5-HT2; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D003577:Cytochrome P-450 Enzyme System