Polymorphisms in GRIK4, HTR2A, and FKBP5 show interactive effects in predicting remission to antidepressant treatment.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Sonja HorstmannElisabeth B Binder

Abstract

Single-nucleotide polymorphisms (SNPs) in the FKBP5, GRIK4, and HTR2A genes have been shown to be associated with response to citalopram treatment in the STAR(*)D sample, but only associations with FKBP5 have so far been tested in the Munich Antidepressant Response Signature (MARS) project. Response and remission of depressive symptoms after 5 weeks of antidepressant treatment were tested against 82 GRIK4 and 37 HTR2A SNPs. Association analysis was conducted in about 300 depressed patients from the MARS project, 10% of whom had bipolar disorder. The most predictive SNPs from these two genes and rs1360780 in FKBP5 were then genotyped in a total of 387 German depressed in-patients to analyze potential additive and interactive effects of these variants. We could not replicate previous findings of the Sequenced Treatment Alternatives to Relieve Depression (STAR(*)D) study in our sample. Although not statistically significant, the effect for the best GRIK4 SNP of STAR(*)D (rs1954787, p=0.076, p(corrected)=0.98) seemed to be in the same direction. On the other hand, the nominally significant association with the top HTR2A SNPs of STAR(*)D (rs7997012, allelic, p=0.043, p(corrected)=0.62) was with the opposite risk allele. The GRIK4 SN...Continue Reading

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