title: Serotonin transporter polymorphism modulates N-back task performance and fMRI BOLD signal intensity in healthy women.
abstract: BACKGROUND
  Exploring intermediate phenotypes within the human brain's functional and structural circuitry is a promising approach to explain the relative contributions of genetics, complex behaviors and neural mechanisms in the development of major depressive disorder (MDD). The polymorphic region 5-HTTLPR in the serotonin transporter gene (SLC6A4) has been shown to modulate MDD risk, but the neural underpinnings are incompletely understood.
  
  
  OBJECTIVE
  37 right handed healthy women between 21 and 61 years of age were invited to participate in an fMRI modified n-back study. The functional polymorphism 5-HTTLPR located in the promoter region of the SLC6A4 gene was genotyped using polymerase chain reaction (PCR).
  
  
  RESULTS
  Short 5-HTTLPR allele carriers showed more blood-oxygen-level-dependent (BOLD) bilateral prefrontal cortex activation in the right [F(2, 30) = 4.8, η(2) = .25, p = .026] and left [F(2, 30) = 4.1, η(2) = .22, p = .015] inferior frontal gyrus pars triangularis with increasing n-back task difficulty relative to long 5-HTTLPR allele carriers. Short 5-HTTLPR allele carriers had inferior task performance on the most difficult n-back condition [F(2, 30) = 4.9, η(2) = .26, p = .014].
  
  
  CONCLUSIONS
  This activation pattern found in healthy at risk individuals resembles an activation pattern that is typically found in patients suffering from acute MDD. Altered function in these areas may reflect intermediate phenotypes and may help explain the increased risk of depression in short 5-HTTLPR allele carriers.
authors.affiliation: Department of Psychology, Center for the Study of Human Cognition, Oslo, Norway. rune.jonassen@psykologi.uio.no
authors.forename: Rune
authors.initials: R
authors.lastname: Jonassen
authors.forename: Tor
authors.initials: T
authors.lastname: Endestad
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
authors.forename: Kari Bente
authors.initials: KB
authors.lastname: Foss Haug
authors.forename: Jens Petter
authors.initials: JP
authors.lastname: Berg
authors.forename: Nils Inge
authors.initials: NI
authors.lastname: Landrø
mesh_terms: D000328:Adult; D001931:Brain Mapping; D003198:Computer Simulation; D003865:Major Depressive Disorder / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006262:Health; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D013647:Task Performance and Analysis; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins