eCite Digital Repository

Impact of 5-HTTLPR on SSRI serotonin transporter blockade during emotion regulation: A preliminary fMRI study


Outhred, T and Das, P and Dobson-Stone, C and Felmingham, KL and Bryant, RA and Nathan, PJ and Malhi, GS and Kemp, AH, Impact of 5-HTTLPR on SSRI serotonin transporter blockade during emotion regulation: A preliminary fMRI study, Journal of Affective Disorders, 196 pp. 11-19. ISSN 0165-0327 (2016) [Refereed Article]

Copyright Statement

Copyright 2016 Elsevier B.V.

DOI: doi:10.1016/j.jad.2016.02.019


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.

Item Details

Item Type:Refereed Article
Keywords:5-HTTLPR, antidepressant, emotion, pharmacogenetics, serotonin, fMRI
Research Division:Health Sciences
Research Group:Health services and systems
Research Field:Mental health services
Objective Division:Health
Objective Group:Public health (excl. specific population health)
Objective Field:Mental health
UTAS Author:Felmingham, KL (Professor Kim Felmingham)
ID Code:108193
Year Published:2016
Web of Science® Times Cited:16
Deposited By:Psychology
Deposited On:2016-04-12
Last Modified:2018-03-22

Repository Staff Only: item control page