title: Impact of 5-HTTLPR on SSRI serotonin transporter blockade during emotion regulation: A preliminary fMRI study.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Tim
authors.initials: T
authors.lastname: Outhred
authors.affiliation: 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.
authors.forename: Pritha
authors.initials: P
authors.lastname: Das
authors.affiliation: Neuroscience Research Australia, Randwick, NSW 2031, Australia; School of Medical Sciences, University of New South Wales, Kensington, NSW 2033, Australia.
authors.forename: Carol
authors.initials: C
authors.lastname: Dobson-Stone
authors.affiliation: School of Psychology, University of Tasmania, Hobart, TAS 7001, Australia.
authors.forename: Kim L
authors.initials: KL
authors.lastname: Felmingham
authors.affiliation: School of Psychology, University of New South Wales, Kensington, NSW 2033, Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bryant
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 1QB, United Kingdom; School of Psychology and Psychiatry, Monash University, VIC 3800, Australia.
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
authors.affiliation: 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.
authors.forename: Gin S
authors.initials: GS
authors.lastname: Malhi
authors.affiliation: 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.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Kemp
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000679:Amygdala / Q000187:drug effects; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D015283:Citalopram / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000187:drug effects; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human
keywords: 5-HTTLPR; Antidepressant; Emotion; Pharmacogenetics; Serotonin; fMRI