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

• Published in: Journal of affective disorders 2016-05, Vol.196, p.11-19
• Main Authors: Outhred, Tim, Das, Pritha, Dobson-Stone, Carol, Felmingham, Kim L, Bryant, Richard A, Nathan, Pradeep J, Malhi, Gin S, Kemp, Andrew H
• Format: Article
• Language: English
• Subjects: 5-HTTLPR; Adolescent; Adult; Alleles; Amygdala - drug effects; Antidepressant; Antidepressive Agents, Second-Generation - pharmacology; Citalopram - pharmacology; Cross-Over Studies; Double-Blind Method; Emotion; Emotions - drug effects; Emotions - physiology; Female; fMRI; Genotype; Healthy Volunteers; Humans; Magnetic Resonance Imaging; Middle Aged; Pharmacogenetics; Polymorphism, Genetic; Prefrontal Cortex - drug effects; Psychiatry; Serotonin; Serotonin Plasma Membrane Transport Proteins - metabolism; Serotonin Uptake Inhibitors - pharmacology; Young Adult
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2016.02.019

Abstract 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.