Reduced amygdala serotonin transporter binding in posttraumatic stress disorder

Biol Psychiatry. 2011 Dec 1;70(11):1033-8. doi: 10.1016/j.biopsych.2011.07.003.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Amygdala / diagnostic imaging
  • Amygdala / drug effects
  • Amygdala / metabolism*
  • Aniline Compounds / pharmacokinetics
  • Brain Mapping
  • Case-Control Studies
  • Female
  • Functional Laterality
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Protein Binding
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Stress Disorders, Post-Traumatic / pathology*
  • Young Adult


  • 2-(2-(dimethylaminomethylphenylthio))-5-fluoromethylphenylamine
  • Aniline Compounds
  • Serotonin Plasma Membrane Transport Proteins