Clinical risk factors and serotonin transporter gene variants associated with antidepressant-induced mania

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dc.contributor.authorFrye, Mark
dc.contributor.authorMcElroy, Susan
dc.contributor.authorPrieto, Miguel
dc.contributor.authorHarper, Kelly
dc.contributor.authorWalker, Denise
dc.contributor.authorKung, Simon
dc.contributor.authorChauhan, Mohit
dc.contributor.authorCrow, Scott
dc.contributor.authorSutor, Bruce
dc.contributor.authorGalardy, Christine
dc.contributor.authorVeldic, Marin
dc.contributor.authorPalmer, Brian
dc.contributor.authorGeske, Jennifer
dc.contributor.authorFuentes, Manuel
dc.contributor.authorCuellar-Barboza, Alfredo
dc.contributor.authorSeymour, Lisa
dc.contributor.authorMori, Nicole
dc.contributor.authorBiernacka, Joanna
dc.date.accessioned2017-05-04T19:07:36Z
dc.date.available2017-05-04T19:07:36Z
dc.date.issued2015
dc.description.abstractINTRODUCTION: Identifying clinical and genetic risk factors associated with antidepressant-induced mania (AIM) may improve individualized treatment strategies for bipolar depression. METHOD: From 2009 to 2012, bipolar depressed patients, confirmed by DSM-IV-TR-structured interview, were screened for AIM. An AIM+ case was defined as a manic/hypomanic episode within 60 days of starting or changing dose of antidepressant, while an AIM- control was defined as an adequate (≥ 60 days) exposure to an antidepressant with no associated manic/hypomanic episode. 591 subjects (205 AIM+ and 386 AIM-) exposed to an antidepressant and a subset of 545 subjects (191 AIM+ and 354 AIM-) treated with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) were used to evaluate the association of AIM with phenotypic clinical risk factors previously published. 295 white subjects (113 AIM+ cases, 182 AIM-controls) were genotyped for 3 SLC6A4 variants: the 5-HTTLPR, single nucleotide polymorphism (SNP) rs25531, and the intron 2 variable number of tandem repeats (VNTR). Tests of association with AIM were performed for each polymorphism and the haplotype. RESULTS: The only clinical risk factors associated with AIM in the overall and the SSRI + SNRI analysis was bipolar I subtype. The S allele of 5-HTTLPR was not significantly associated with AIM; however, a meta-analysis combining this sample with 5 prior studies provided marginal evidence of association (P = .059). The L-A-10 haplotype was associated with a reduced risk of AIM (P = .012). DISCUSSION: Narrowly defined, AIM appears to be at greatest risk for bipolar I patients. Our haplotype analysis of SLC6A4 suggests that future pharmacogenetic studies should not only focus on the SLC6A4 promotor variation but also investigate the role of other variants in the gene.
dc.format.extent7
dc.identifier.citationJ Clin Psychiatry. 2015 Feb;76(2):174-80
dc.identifier.urihttp://hdl.handle.net/11447/1191
dc.identifier.urihttp://dx.doi.org/10.4088/JCP.14m09127
dc.language.isoen_US
dc.publisherMemphis, Tenn., Physicians Postgraduate Press
dc.subjectBipolar Disorder/chemically induced
dc.subjectBipolar Disorder/genetics
dc.subjectGenetic Variation/genetics
dc.subjectSerotonin Plasma Membrane Transport Proteins/genetics
dc.subjectSerotonin Uptake Inhibitors/adverse effects
dc.titleClinical risk factors and serotonin transporter gene variants associated with antidepressant-induced mania
dc.typeArtículo

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