The Effect of Early Trauma Exposure on Serotonin Type 1B Receptor Expression Revealed by Reduced Selective Radioligand Binding

Context: Serotonergic dysfunction is implicated in the pathogenesis of posttraumatic stress disorder (PTSD), and recent animal models suggest that disturbances in serotonin type 1B receptor function, in particular, may contribute to chronic anxiety. However, the specific role of the serotonin type 1B receptor has not been studied in patients with PTSD. Objective: To investigate in vivo serotonin type 1B receptor expression in individuals with PTSD, trauma-exposed control participants without PTSD (TC), and healthy (nontrauma-exposed) control participants (HC) using positron emission tomography and the recently developed serotonin type 1B receptor selective radiotracer [C-11] P943. Design: Cross-sectional positron emission tomography study under resting conditions. Setting: Academic and Veterans Affairs medical centers. Participants: Ninety-six individuals in 3 study groups: PTSD (n=49), TC (n=20), and HC (n=27). Main Outcome Measure: Regional [C-11] P943 binding potential (BPND) values in an a priori-defined limbic corticostriatal circuit investigated using multivariate analysis of variance and multiple regression analysis. Results: A history of severe trauma exposure in the PTSD and TC groups was associated with marked reductions in [C-11] P943 BPND in the caudate, the amygdala, and the anterior cingulate cortex. Participant age at first trauma exposure was strongly associated with low [C-11] P943 BPND. Developmentally earlier trauma exposure also was associated with greater PTSD symptom severity and major depression comorbidity. Conclusions: These data suggest an enduring effect of trauma history on brain function and the phenotype of PTSD. The association of early age at first trauma and more pronounced neurobiological and behavioral alterations in PTSD suggests a developmental component in the cause of PTSD.