title: Reduced amygdala serotonin transporter binding in posttraumatic stress disorder.
abstract: BACKGROUND
  The amygdala is a key site where alterations in the regulation of the serotonin transporter (5-HTT) may alter stress response. Deficient 5-HTT function and abnormal amygdala activity have been hypothesized to contribute to the pathophysiology of posttraumatic stress disorder (PTSD), but no study has evaluated the 5-HTT in humans with PTSD. On the basis of translational models, we hypothesized that patients diagnosed with PTSD would exhibit reduced amygdala 5-HTT expression as measured with positron emission tomography and the recently developed 5-HTT-selective radiotracer [(11)C]AFM.
  
  
  METHODS
  Fifteen participants with PTSD and 15 healthy control (HC) subjects without trauma history underwent a resting-state positron emission tomography scan.
  
  
  RESULTS
  [(11)C]AFM binding potential (BP(ND)) within the combined bilateral amygdala region of interest was significantly reduced in the PTSD group compared with the HC group (p = .027; 16.3% reduction), which was largely driven by the between-group difference in the left amygdala (p = .008; 20.5% reduction). Furthermore, amygdala [(11)C]AFM BP(ND) was inversely correlated with both Hamilton Rating Scale for Anxiety scores (r = -.55, p = .035) and Montgomery-Åsberg Depression Rating Scale scores (r = -.56, p = .029).
  
  
  CONCLUSIONS
  Our findings of abnormally reduced amygdala 5-HTT binding in PTSD and its association with higher anxiety and depression symptoms in PTSD patients support a translational neurobiological model of PTSD directly implicating dysregulated 5-HTT signaling within neural systems underlying threat detection and fear learning.
authors.affiliation: Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Murrough
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.forename: Shannan
authors.initials: S
authors.lastname: Henry
authors.forename: Wendol
authors.initials: W
authors.lastname: Williams
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Gallezot
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Bailey
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D000814:Aniline Compounds / Q000493:pharmacokinetics; D001931:Brain Mapping; D016022:Case-Control Studies; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011485:Protein Binding; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000473:pathology*; D055815:Young Adult
chemical_list: C482405:2-(2-(dimethylaminomethylphenylthio))-5-fluoromethylphenylamine; D000814:Aniline Compounds; D050486:Serotonin Plasma Membrane Transport Proteins