title: Relationship of the serotonin transporter gene promoter polymorphism (5-HTTLPR) genotype and serotonin transporter binding to neural processing of negative emotional stimuli.
abstract: BACKGROUND
  The lower-expressing (S') alleles of the serotonin transporter (5-HTT) gene promoter polymorphism (5-HTTLPR) are linked to mood and anxiety related psychopathology. However, the specific neural mechanism through which these alleles may influence emotional and cognitive processing remains unknown. We examined the relationship between both 5-HTTLPR genotype and in vivo 5-HTT binding quantified via PET with amygdala reactivity to emotionally negative stimuli. We hypothesized that 5-HTT binding in both raphe nuclei (RN) and amygdala would be inversely correlated with amygdala reactivity, and that number of S' alleles would correlate positively with amygdala reactivity.
  
  
  METHODS
  In medication-free patients with current major depressive disorder (MDD; N=21), we determined 5-HTTLPR genotype, employed functional magnetic resonance imaging (fMRI) to examine amygdala responses to negative emotional stimuli, and used positron emission tomography with [(11)C]DASB to examine 5-HTT binding.
  
  
  RESULTS
  [(11)C]DASB binding in RN and amygdala was inversely correlated with amygdala response to negative stimuli. 5-HTTLPR S' alleles were not associated with amygdala response to negative emotional stimuli.
  
  
  CONCLUSIONS
  Primary limitations are small sample size and lack of control group.
  
  
  CONCLUSIONS
  Consistent with findings in healthy volunteers, 5-HTT binding is associated with amygdala reactivity to emotional stimuli in MDD. 5-HTT binding may be a stronger predictor of emotional processing in MDD as compared with 5-HTTLPR genotype.
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, United States; Department of Psychiatry, Columbia University, New York, NY, United States. Electronic address: schneck@nyspi.columbia.edu.
authors.forename: Noam
authors.initials: N
authors.lastname: Schneck
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, United States; Department of Psychiatry, Columbia University, New York, NY, United States.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Miller
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, United States; Department of Psychiatry and Behavioral Science, Stony Brook University School of Medicine, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Delorenzo
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, United States; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, United States; Department of Psychiatry, Columbia University, New York, NY, United States.
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Sublette
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, United States; Department of Psychiatry, Columbia University, New York, NY, United States.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, United States; Department of Psychiatry, Columbia University, New York, NY, United States.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.affiliation: Department of Psychiatry and Behavioral Science, Stony Brook University School of Medicine, United States.
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
mesh_terms: D000328:Adult; D000483:Alleles; D000679:Amygdala / Q000378:metabolism; D001596:Benzylamines / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000378:metabolism; D003865:Major Depressive Disorder / Q000235:genetics* / Q000378:metabolism*; D004644:Emotions / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography; D011401:Promoter Regions, Genetic; D011869:Radioligand Assay; D011903:Raphe Nuclei / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001596:Benzylamines; D002250:Carbon Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: Biological Markers; Brain Imaging; Depression; Functional MRI; Genetics