Higher in vivo serotonin-1A binding in posttraumatic stress disorder: A pet study with [¹¹C]WAY-100635

Background Brain serotonin-1A receptors (5-HT_1A) are implicated in anxiety. We compared regional brain 5-HT_1A binding in medication-free participants with posttraumatic stress disorder (PTSD) and healthy volunteers using fully quantitative positron emission tomography (PET) methods. Methods Twenty patients with DSM-IV PTSD (13 with comorbid major depressive disorder, [MDD]) and 49 healthy volunteers underwent PET imaging with 5-HT_1A antagonist radioligand [C-11]WAY100635. Arterial blood sampling provided a metabolite-corrected input function and the concentration of free ligand in plasma (f_P) for estimation of regional binding potential, BP_F (= B_available / K_D). Linear mixed modeling compared BP_F between groups across regions of interest (ROIs). Results The PTSD group had higher 5-HT_1A BP_F across brain ROIs (P =.0006). Post hoc comparisons showed higher 5-HT _1A BP_F in PTSD in all cortical ROIs (26-33%), amygdala (34%), and brainstem raphe nuclei (43%), but not hippocampus. The subgroup of seven PTSD patients without comorbid MDD had higher 5-HT_1A BP _F compared with healthy volunteers (P =.03). Conclusions This is the first report of higher brainstem and forebrain 5-HT_1A binding in vivo in PTSD. The finding is independent of MDD. PTSD and MDD have in common an upregulation of 5-HT_1A binding including midbrain autoreceptors that would favor less firing and serotonin release. This abnormality may represent a common biomarker of these stress-associated brain disorders.