title: Understanding the pharmacogenetics of selective serotonin reuptake inhibitors.
abstract: BACKGROUND
  The genetic background of antidepressant response represents a unique opportunity to identify biological markers of treatment outcome. Encouraging results alternating with inconsistent findings made antidepressant pharmacogenetics a stimulating but often discouraging field that requires careful discussion about cumulative evidence and methodological issues.
  
  
  METHODS
  The present review discusses both known and less replicated genes that have been implicated in selective serotonin reuptake inhibitors (SSRIs) efficacy and side effects. Candidate genes studies and genome-wide association studies (GWAS) were collected through MEDLINE database search (articles published till January 2014). Further, GWAS signals localized in promising genetic regions according to candidate gene studies are reported in order to assess the general comparability of results obtained through these two types of pharmacogenetic studies. Finally, a pathway enrichment approach is applied to the top genes (those harboring SNPs with p < 0.0001) outlined by previous GWAS in order to identify possible molecular mechanisms involved in SSRI effect.
  
  
  CONCLUSIONS
  In order to improve the understanding of SSRI pharmacogenetics, the present review discusses the proposal of moving from the analysis of individual polymorphisms to genes and molecular pathways, and from the separation across different methodological approaches to their combination. Efforts in this direction are justified by the recent evidence of a favorable cost-utility of gene-guided antidepressant treatment.
authors.affiliation: University of Bologna, Institute of Psychiatry, Department of Biomedical and NeuroMotor Sciences , Viale Carlo Pepoli 5, 40123 Bologna , Italy +39 051 6584233 ; +39 051 521030 ; alessandro.serretti@unibo.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fabbri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Minarini
authors.forename: Tomihisa
authors.initials: T
authors.lastname: Niitsu
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D055106:Genome-Wide Association Study; D006801:Humans; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D017367:Selective Serotonin Reuptake Inhibitors
keywords: antidepressant; depression; gene; genome-wide; genome-wide association studies; pathway; pharmacogenetics; pharmacogenomics; polymorphism; serotonin reuptake inhibitor