Browsing by Author "Harper, Kelly"
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Item Clinical risk factors and serotonin transporter gene variants associated with antidepressant-induced mania(Memphis, Tenn., Physicians Postgraduate Press, 2015) Frye, Mark; McElroy, Susan; Prieto, Miguel; Harper, Kelly; Walker, Denise; Kung, Simon; Chauhan, Mohit; Crow, Scott; Sutor, Bruce; Galardy, Christine; Veldic, Marin; Palmer, Brian; Geske, Jennifer; Fuentes, Manuel; Cuellar-Barboza, Alfredo; Seymour, Lisa; Mori, Nicole; Biernacka, JoannaINTRODUCTION: 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.