The impact of 5-HTTLPR on acute serotonin transporter blockade by escitalopram on emotion processing: Preliminary findings from a randomised, crossover fMRI study

Objective: Benefit from antidepressant treatment such as selective serotonin reuptake inhibitors (SSRIs) may depend on individual differences in acute effects on neural emotion processing. The short (‘S’) allele of the serotonin transporter (5-HTT)-linked polymorphic region (5-HTTLPR) is associated with both negative emotion processing biases and poorer treatment outcomes. Therefore, the aim of the present study was to explore the effects of 5-HTTLPR on the impact of the SSRI escitalopram during processing of positive and negative emotional images, as well as neutral stimuli.

Methods: The study employed a double-blind, randomised, placebo-controlled crossover design on 36 healthy Caucasian female participants who underwent functional magnetic resonance imaging (fMRI) scanning following placebo or escitalopram treatment, separated by a 7-day washout period.

Results: Changes in the left amygdala signal with escitalopram treatment during processing of emotional stimuli were linearly related to the 5-HTTLPR ‘S’ allele load such that the signal to positive stimuli decreased and the signal to negative stimuli increased with an increasing number of low-expressing ‘S’ alleles. While 5-HTTLPR subgroups were small in size, individual subject changes with treatment and task condition increase confidence in the findings.

Conclusions: While preliminary, our findings comprise the first pharmacogenetic study demonstrating an effect of the 5-HTTLPR ‘S’ allele load on escitalopram-induced changes in amygdala activity during emotional processing, consistent with a 5-HTT expression dosage model. The present findings have implications for the impact of this polymorphism on antidepressant efficacy in patients with mood and anxiety disorders.