1. Pharmacogenetics of major depressive disorder: top genes and pathways toward clinical applications
- Author
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Chiara Fabbri, Alessandro Serretti, Fabbri, Chiara, and Serretti, Alessandro
- Subjects
Candidate gene ,CYP2D6 ,ATP Binding Cassette Transporter, Subfamily B ,Genotype ,Antidepressant ,Genome-wide association study ,Major depressive disorder ,CYP2C19 ,Biology ,Bioinformatics ,Gene ,Cytochrome P-450 Enzyme System ,medicine ,Humans ,Polymorphism ,Genetics ,Serotonin Plasma Membrane Transport Proteins ,Depressive Disorder, Major ,Neuronal Plasticity ,Pharmacogenetic ,P-Glycoprotein ,medicine.disease ,Antidepressive Agents ,Psychiatry and Mental health ,Pharmacogenetics ,Antidepressive Agent ,FKBP5 ,Receptors, Serotonin, 5-HT2 ,Serotonin Plasma Membrane Transport Protein ,Pathway ,Human ,Genome-Wide Association Study ,Signal Transduction - 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.
- Published
- 2015