title: The impact of 5-HTTLPR on acute serotonin transporter blockade by escitalopram on emotion processing: preliminary findings from a randomised, crossover fMRI study.
abstract: 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.
authors.affiliation: Discipline of Psychiatry, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St Leonards, Australia SCAN Research and Teaching Unit, School of Psychology, University of Sydney, Sydney, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Outhred
authors.affiliation: Discipline of Psychiatry, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St Leonards, Australia CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, St Leonards, Australia Advanced Research and Clinical Highfield Imaging (ARCHI), University of Sydney, Royal North Shore Hospital, St Leonards, Australia.
authors.forename: Pritha
authors.initials: P
authors.lastname: Das
authors.affiliation: Neuroscience Research Australia, Randwick, Australia School of Medical Sciences, University of New South Wales, Kensington, Australia.
authors.forename: Carol
authors.initials: C
authors.lastname: Dobson-Stone
authors.affiliation: School of Psychology, University of Tasmania, Hobart, Australia.
authors.forename: Kim L
authors.initials: KL
authors.lastname: Felmingham
authors.affiliation: School of Psychology, University of New South Wales, Kensington, Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bryant
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom School of Psychology and Psychiatry, Monash University, Clayton, Australia.
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
authors.affiliation: Discipline of Psychiatry, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St Leonards, Australia CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, St Leonards, Australia Advanced Research and Clinical Highfield Imaging (ARCHI), University of Sydney, Royal North Shore Hospital, St Leonards, Australia.
authors.forename: Gin S
authors.initials: GS
authors.lastname: Malhi
authors.affiliation: Discipline of Psychiatry, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St Leonards, Australia SCAN Research and Teaching Unit, School of Psychology, University of Sydney, Sydney, Australia CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, St Leonards, Australia Advanced Research and Clinical Highfield Imaging (ARCHI), University of Sydney, Royal North Shore Hospital, St Leonards, Australia Hospital Universitário, Universidade de São Paulo, São Paulo, Brazil andrew.kemp@hu.usp.br andrew.kemp@sydney.edu.au.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Kemp
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D001931:Brain Mapping; D015283:Citalopram / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects* / Q000502:physiology; D005260:Female; D059907:Functional Neuroimaging; D018628:Gene Dosage; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D020641:Polymorphism, Single Nucleotide; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D015283:Citalopram; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human
keywords: 5-HTTLPR; Antidepressant; emotion; fMRI; pharmacogenetics; serotonin