Tim Outhred1, Pritha Das2, Carol Dobson-Stone3, Kim L Felmingham4, Richard A Bryant5, Pradeep J Nathan6, Gin S Malhi2, Andrew H Kemp7. 1. Academic Department of Psychiatry, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW 2065, Australia; Sydney Medical School Northern, University of Sydney, NSW 2006, Australia. 2. Academic Department of Psychiatry, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW 2065, Australia; Sydney Medical School Northern, University of Sydney, NSW 2006, Australia; CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW 2065, Australia; Advanced Research and Clinical Highfield Imaging (ARCHI), University of Sydney, Royal North Shore Hospital, NSW 2065, Australia. 3. Neuroscience Research Australia, Randwick, NSW 2031, Australia; School of Medical Sciences, University of New South Wales, Kensington, NSW 2033, Australia. 4. School of Psychology, University of Tasmania, Hobart, TAS 7001, Australia. 5. School of Psychology, University of New South Wales, Kensington, NSW 2033, Australia. 6. Department of Psychiatry, University of Cambridge, Cambridge CB2 1QB, United Kingdom; School of Psychology and Psychiatry, Monash University, VIC 3800, Australia. 7. Academic Department of Psychiatry, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW 2065, Australia; Sydney Medical School Northern, University of Sydney, NSW 2006, Australia; CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW 2065, Australia; Advanced Research and Clinical Highfield Imaging (ARCHI), University of Sydney, Royal North Shore Hospital, NSW 2065, Australia; Department of Psychology, College of Human and Health Sciences, Swansea University, Vivian Tower, Singleton Park, SWANSEA SA2 8PP, United Kingdom. Electronic address: A.H.Kemp@swansea.ac.uk.
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 twofMRI 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.
RCT Entities:
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.
Authors: Víctor Pérez; Ariana Salavert; Jordi Espadaler; Miquel Tuson; Jerónimo Saiz-Ruiz; Cristina Sáez-Navarro; Julio Bobes; Enrique Baca-García; Eduard Vieta; José M Olivares; Roberto Rodriguez-Jimenez; José M Villagrán; Josep Gascón; Josep Cañete-Crespillo; Montse Solé; Pilar A Saiz; Ángela Ibáñez; Javier de Diego-Adeliño; José M Menchón Journal: BMC Psychiatry Date: 2017-07-14 Impact factor: 3.630