title: ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression.
abstract: The hypothesis that allelic variation in the multidrug resistance-1 (MDR1 or ABCB1) gene encoding the P-glycoprotein (P-gp) blood-brain barrier efflux pump is associated with remission and side effects was tested in chronic major depression patients treated with P-gp substrates. In 83 patients from the REVAMP trial, frequency of and time to remission as well as side effects was tested among genotype groups at 6 ABCB1 single nucleotide polymorphisms (SNPs). These six SNPs are significantly associated with remission and time to remission, with minor allele carriers on rs2235040 and rs9282564 attaining statistical significance after controlling for the other ABCB1 SNPs. The six ABCB1 SNPs are also significantly associated with the average side effects. However, here common homozygotes on rs2235040 and rs9282564 demonstrated significantly higher side effects after controlling for the effects of the other ABCB1 SNPs. These findings confirm and extend previous observations that minor alleles of two ABCB1 SNPs predict remission to treatment with substrates and demonstrate that common homozygotes on these SNPs experience greater side effects. Results point to the potential importance of ABCB1 variation for personalized medicine approaches to treating depression.
authors.affiliation: Department of Psychiatry, Stanford University, Stanford, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ray
authors.affiliation: Department of Psychiatry, Stanford University, Stanford, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Tennakoon
authors.affiliation: Department of Psychiatry, Stanford University, Stanford, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Keller
authors.affiliation: Department of Psychiatry, Stanford University, Stanford, CA, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Sarginson
authors.affiliation: Department of Psychiatry, Stanford University, Stanford, CA, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Ryan
authors.affiliation: Department of Psychiatry, Stanford University, Stanford, CA, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Murphy
authors.affiliation: Department of Psychiatry, Stanford University, Stanford, CA, USA.
authors.forename: L C
authors.identifier: 0000000218466920
authors.initials: LC
authors.lastname: Lazzeroni
authors.affiliation: Department of Psychiatry, Stanford University, Stanford, CA, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Trivedi
authors.affiliation: Department of Psychiatry, Stanford University, Stanford, CA, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Kocsis
authors.affiliation: Department of Psychiatry, Stanford University, Stanford, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: DeBattista
authors.affiliation: Department of Psychiatry, Stanford University, Stanford, CA, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Schatzberg
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000483:Alleles; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020280:Sertraline / Q000627:therapeutic use; D016896:Treatment Outcome; D044465:White People
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000928:Antidepressive Agents; D020280:Sertraline