Reduced amygdala serotonin transporter binding in posttraumatic stress disorder

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 [ ¹¹C]AFM. Methods: Fifteen participants with PTSD and 15 healthy control (HC) subjects without trauma history underwent a resting-state positron emission tomography scan. Results: [ ¹¹C]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 [ ¹¹C]AFM BP _ND was inversely correlated with both Hamilton Rating Scale for Anxiety scores (r = -.55, p =.035) and Montgomerysberg 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.