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

JOURNAL OF AFFECTIVE DISORDERS

卷:196

Article

Outhred, Tim^1,2  Das, Pritha^1,2,3,4  Dobson-Stone, Carol^5,6  Felmingham, Kim L.⁷  Bryant, Richard A.⁸  Nathan, Pradeep J.^9,10  Malhi, Gin S.^1,2,3,4  Kemp, Andrew H.^1,2,3,4,11 

[1] Kolling Inst, Acad Dept Psychiat, St Leonards, NSW 2065, Australia

[2] Univ Sydney, Sydney Med Sch Northern, Sydney, NSW 2006, Australia

[3] Royal N Shore Hosp, CADE Clin, St Leonards, NSW 2065, Australia

[4] Univ Sydney, Royal N Shore Hosp, ARCHI, St Leonards, NSW 2065, Australia

[5] Neurosci Res Australia, Randwick, NSW 2031, Australia

[6] Univ New S Wales, Sch Med Sci, POB 1, Kensington, NSW 2033, Australia

[7] Univ Tasmania, Sch Psychol, Hobart, Tas 7001, Australia

[8] Univ New S Wales, Sch Psychol, POB 1, Kensington, NSW 2033, Australia

[9] Univ Cambridge, Dept Psychiat, Cambridge CB2 1QB, England

[10] Monash Univ, Sch Psychol & Psychiat, Clayton, Vic 3800, Australia

[11] Swansea Univ, Coll Human & Hlth Sci, Dept Psychol, Vivian Tower,Singleton Pk, Swansea SA2 8PP, W Glam, Wales

关键词: Antidepressant;    5-HTTLPR;    Emotion;    Serotonin;    Pharmacogenetics;    fMRI;   

DOI  :  10.1016/j.jad.2016.02.019

来源: Elsevier

【 摘 要 】

Background: The short ('S') allele of the serotonin transporter (5-HTT)-linked polymorphic region (5HTTLPR) 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. (C) 2016 Elsevier B.V. All rights reserved.

【 授权许可】

Free