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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
ABCB1 polymorphism predicts escitalopram dose needed for remission in major depression
Translational Psychiatry, Volume 2, Article e198, Year 2012
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Description
The ATP-binding cassette family of transporter proteins, subfamily B (MDR/TAP), member 1 (ABCB1) (P-glycoprotein) transporter is a key component of the blood-brain barrier. Many antidepressants are subject to ABCB1 efflux. Functional polymorphisms of ABCB1 may influence central nervous system bioavailability of antidepressants subject to efflux. Single-nucleotide polymorphisms (SNPs) at rs1045642 (C3435T) of ABCB1 have been associated with efflux pump efficiency. This may explain part of the interindividual variation in antidepressant dose needed to remit. Individuals (N113) with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) major depressive disorder (MDD) were treated with escitalopram (ESC) or venlafaxine (VEN) over 8 weeks. The17-item Hamilton Depression Rating Scale was assessed serially, blind to genotype. SNP rs1045642 of ABCB1 along with two SNPs previously reported to be in linkage disequilibrium with it (rs2032582 and rs1128503) were genotyped. Demographic features, clinical features, P450 metabolizer status and 5-HTTLPR (serotonin-transporter-linked promoter region) genotype were controlled for. Carriers of rs1045642 TT needed on average 11 mg of ESC to remit, whereas TC and CC carriers required 24 and 19 mg, respectively (P<0.0001). This equates to a 2.0-(95% confidence interval1.5-3.4; P<0.001) fold greater ESC dose needed to remit for C carriers compared with TT carriers at rs1045642. Of VEN-treated subjects carrying TT genotype at rs1045642, 73.3% remitted compared with 12.5% for CC genotype (odds ratio6.69; 95% confidence interval1.72-25.9, P<0.006). These data suggest that antidepressant dose needed to remit can be predicted by an ABCB1 SNP. This has the potential clinical translation implications for dose selection and remission from MDD. © 2012 Macmillan Publishers Limited All rights reserved.
Authors & Co-Authors
Bousman, Chad A.
Australia, Melbourne
University of Melbourne
Australia, Hawthorn
Swinburne University of Technology
Australia, Melbourne
The Florey
Ng, Chee H.
Australia, Melbourne
University of Melbourne
Berk, Michael
Australia, Geelong
Deakin University
Australia, Melbourne
University of Melbourne
Australia, Melbourne
The Florey
Australia, Melbourne
Orygen Youth Health
Statistics
Citations: 68
Authors: 3
Affiliations: 5
Identifiers
Doi:
10.1038/tp.2012.115
ISSN:
21583188
Research Areas
Disability
Genetics And Genomics
Mental Health
Substance Abuse