Greer Murphy M.D., Ph.D.
Publication Details
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BDNF and CREB1 genetic variants interact to affect antidepressant treatment outcomes in geriatric depression
Pharmacogenetics and Genomics. 2013
Brain derived neurotrophic factor (BDNF) is associated with antidepressant response on the cellular level, in animal models, and in clinical studies. A common variant in the BDNF gene results in a substitution of a methionine (Met) for a valine (Val) at amino acid position 66. Prior studies reported that the Met variant results in enhanced response to antidepressant medications. These findings may be at odds with studies indicating that on a cellular level the Met variant impairs BDNF secretion. We examined the effects of BDNF single nucleotide polymorphisms (SNPs) on response to the antidepressants paroxetine and mirtazapine in a sample of 246 geriatric patients with major depression treated in a double-blind, randomized 8-week clinical trial. We also examined the effects of genetic variation at the BDNF-related loci NTRK2, CREB1, and CREBBP. A total of 53 SNPs were genotyped. BDNF genetic variation had a significant effect on the efficacy of paroxetine, with patients carrying the Met allele showing impaired response. SNPs at the CREB1 locus, which encodes a transcription factor important in BDNF signaling, also predicted response to paroxetine. Furthermore, we found a significant gene-gene interaction between BDNF and CREB1 that affected response to paroxetine. Because BDNF has been associated with cognitive function, we tested the effects of BDNF SNPs on change in a wide variety of cognitive tests over the 8-week trial. These results provide new evidence for the importance of the BDNF pathway in antidepressant response in geriatric patients.
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