title: Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy.
abstract: The majority of antidepressant drugs act by increasing synaptic serotonin levels in the brain. Genetic variation in serotonin-related genes may therefore influence antidepressant efficacy. In this study, nine polymorphisms in four serotonin receptor genes (HTR1B, HTR2A, HTR5A and HTR6) and the serotonin transporter gene (SLC6A4) were analysed to investigate their influence on antidepressant response in a well-characterized unipolar depressive population (n=166) following a protocolized treatment regimen. 5-HTTLPR short-allele homozygotes were significantly associated with both remission (odds ratios (OR)=4.00, P=0.04) and response (OR=5.06, P=0.02) following second switch treatment, with a similar trend observed following initial treatment and paroxetine therapy. Following initial treatment, unipolar patients homozygous for the SLC6A4 intron 2 repeat polymorphism were significantly associated with lack of remission (OR=0.38, P=0.02) and lack of response (OR=0.42, P=0.01). Additionally, the HTR2A C(1354)T polymorphism showed an association with remission (OR=7.50, P=0.002) and response (OR=5.25, P=0.01) following paroxetine therapy. These results suggest that genetically determined variation in serotonin receptor genes makes a significant contribution to the efficacy of commonly prescribed antidepressant drugs.
authors.affiliation: Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: M J V
authors.initials: MJ
authors.lastname: Wilkie
authors.forename: G
authors.initials: G
authors.lastname: Smith
authors.forename: R K
authors.initials: RK
authors.lastname: Day
authors.forename: K
authors.initials: K
authors.lastname: Matthews
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Blackwood
authors.forename: I C
authors.initials: IC
authors.lastname: Reid
authors.forename: C R
authors.initials: CR
authors.lastname: Wolf
mesh_terms: D000928:Antidepressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D017374:Paroxetine / Q000493:pharmacokinetics / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D044402:Receptor, Serotonin, 5-HT2A; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D017374:Paroxetine