Decreased Pretreatment Amygdalae Serotonin Transporter Binding in Unipolar Depression Remitters: A Prospective PET Study.

Major depressive disorder (MDD) is a debilitating condition that affects over 14 million Americans. Remission occurs only in a minority of individuals after first-line antidepressant treatment (∼35%); predictors of treatment outcome are therefore needed. Using PET imaging with a radiotracer specific for the serotonin transporter (5-HTT), C-McN5652, we found that patients with MDD who did not achieve remission after 12 mo of naturalistic treatment had lower pretreatment midbrain and amygdala binding than healthy volunteers. Here, using a superior 5-HTT tracer, C-DASB, we repeated this study with a prospective design with 8 wk of standardized treatment with escitalopram. As this same cohort also underwent C-WAY100635 scans (serotonin-1A receptor [5-HT]), we examined whether using both pretreatment 5-HTT and 5-HT binding could improve prediction of posttreatment remission status. Thirty-one healthy controls (Hamilton Depression Rating Scale-24 item [HDRS-24] = 1.7) and 26 medication-free patients with MDD (HDRS-24 = 24.8) underwent PET scanning using C-DASB. MDD subjects then received 8 wk of standardized pharmacotherapy with escitalopram. The relationship between pretreatment binding and posttreatment clinical status was examined. Arterial blood samples were collected to calculate the metabolite-corrected arterial input function. The outcome measure was V/f (V is volume of distribution in region of interest, f is free fraction in plasma). Remission was defined as a posttreatment depression score of less than 10 as well as 50% or more reduction in the score from baseline, resulting in 14 nonremitters (HDRS-24 = 17.6) and 12 remitters (HDRS-24 = 5.3). A linear mixed-effects model comparing group differences in the a priori regions of interest (amygdala and midbrain) revealed a significant difference in amygdala binding between controls and remitters ( = 0.03, unadjusted), where remitters had an 11% lower amygdala binding than controls. Differences in amygdala binding between remitters and nonremitters approached significance ( = 0.06). No additional differences were found between any groups (all > 0.05). Additionally, we found no relationship between pretreatment amygdala binding and posttreatment depression score, and were unable to predict posttreatment depression severity using both pretreatment 5-HTT (in the amygdala) and 5-HT binding (in the raphe). These results suggest 5-HTT amygdala binding should be examined further, in conjunction with other measures, as a potential biomarker for remission after standardized escitalopram treatment.

© 2018 by the Society of Nuclear Medicine and Molecular Imaging.