Impact of 5 HTTLPR on SSRI serotonin transporter blockade during emotion regulation: A preliminary fMRI study.
BACKGROUND The short 'S' allele of the serotonin transporter (5 HTT) linked polymorphic region (5 HTTLPR) is associated with increased negative emotion processing bias, and this polymorphism moderates acute effects of selective serotonin reuptake inhibitor (SSRI) treatment. In this preliminary study, we explore the moderating effect of 5 HTTLPR on the impact of the SSRI, escitalopram during emotion regulation of negative emotional stimuli. METHOD Thirty six healthy Caucasian, female participants underwent two fMRI scanning sessions following single dose escitalopram and placebo administration separated by a seven day washout period according to a double blind, randomized, placebo controlled crossover design. Functional connectivity analysis was employed with a left (L) amygdala seed and a right interior frontal gyrus (R IFG) target. RESULTS Changes in functional connectivity with emotion regulation and treatment were linearly related to 5 HTTLPR 'L' allele load such that negative R IFG L amygdala connectivity was increased with an increasing number of 'L' alleles. Therefore, escitalopram may facilitate the effects of reappraisal by enhancing negative functional connectivity, a finding that is greatest in participants homozygous for the 'L' allele and least in those homozygous for the 'S' allele. LIMITATIONS Sub samples of the homozygote 'S/S' and 'L/L' 5 HTTLPR groupings were small. However, the within subjects nature of the experiment and observing changes at the individual subject level increases our confidence in the findings of the present study. CONCLUSIONS The present study elucidates a potential neural mechanism by which antidepressant treatment produces differential treatment outcomes dependent on the 5 HTTLPR polymorphism, providing new and important leads for models of antidepressant action.
Journal of affective disorders