Title

Serotonergic polymorphisms mediate a weakened response to SSRI treatment: a proposed model

Date

5-28-2015 4:45 PM

End Time

28-5-2015 5:00 PM

Location

Natural Sciences (NS) 103

Department

Biology

Session Chair

Ava Howard

Session Chair

Jeffrey Snyder

Session Title

Research in the Biological Sciences

Faculty Sponsor(s)

Mike Baltzley

Presentation Type

Presentation

Abstract

Individuals with the short (S) allele in the promoter region of the serotonin transporter gene (5-HTTLPR) show a less favorable response to selective serotonin reuptake inhibitor (SSRI) treatment than individuals with the long (L) allele. Similarly, individuals with the C(-1019)G polymorphism in the promoter region of the serotonin 1A receptor gene (5-HTR1A) have shown blunted responses to SSRI treatment when compared with individuals lacking this polymorphism. While these findings have been replicated across multiple studies, only two studies to date have reported data for a gene-gene interaction associated with response to SSRI treatment. Both of these studies reported a combined effect for these genotypes, with individuals homozygous for the L allele and the C allele (5-HTTL/L – 1AC/C) reporting the most favorable response to SSRI treatment and individuals homozygous for the S allele and the G allele (5-HTTS/S – 1AG/G) reporting the least favorable response to SSRI treatment. Additionally, no neural mechanisms have been proposed to explain why this gene-gene interaction has been observed. To that end, this presentation provides a review of the relevant literature associated with these polymorphisms and proposes a feasible model that describes a genotype-dependent modulation of postsynaptic serotonin signaling associated with the 5-HTT and 5HTR1A gene.

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May 28th, 4:45 PM May 28th, 5:00 PM

Serotonergic polymorphisms mediate a weakened response to SSRI treatment: a proposed model

Natural Sciences (NS) 103

Individuals with the short (S) allele in the promoter region of the serotonin transporter gene (5-HTTLPR) show a less favorable response to selective serotonin reuptake inhibitor (SSRI) treatment than individuals with the long (L) allele. Similarly, individuals with the C(-1019)G polymorphism in the promoter region of the serotonin 1A receptor gene (5-HTR1A) have shown blunted responses to SSRI treatment when compared with individuals lacking this polymorphism. While these findings have been replicated across multiple studies, only two studies to date have reported data for a gene-gene interaction associated with response to SSRI treatment. Both of these studies reported a combined effect for these genotypes, with individuals homozygous for the L allele and the C allele (5-HTTL/L – 1AC/C) reporting the most favorable response to SSRI treatment and individuals homozygous for the S allele and the G allele (5-HTTS/S – 1AG/G) reporting the least favorable response to SSRI treatment. Additionally, no neural mechanisms have been proposed to explain why this gene-gene interaction has been observed. To that end, this presentation provides a review of the relevant literature associated with these polymorphisms and proposes a feasible model that describes a genotype-dependent modulation of postsynaptic serotonin signaling associated with the 5-HTT and 5HTR1A gene.