3 years ago

Decreased pretreatment amygdalae serotonin transporter binding in unipolar depression remitters: a prospective PET study.

Yang J, Parsey R, Ananth M, Mann JJ, DeLorenzo C
Major Depressive Disorder (MDD) is a debilitating condition that affects over 14 million Americans. Remission only occurs in a minority of individuals following first-line antidepressant treatment (~35%); predictors of treatment outcome are therefore needed. Using Positron Emission Tomography (PET) imaging with a radiotracer specific for the serotonin transporter (5-HTT), 11C-McN5652, we found that patients with MDD who did not achieve remission following 12 months of naturalistic treatment had lower pre-treatment midbrain and amygdala binding compared to healthy volunteers. Here, using a superior 5-HTT tracer, 11C-DASB, we repeated this study with a prospective design with 8 weeks of standardized treatment with escitalopram. As this same cohort also received 11C-WAY100635 scans (5-HT1A), we examined whether using both pre-treatment 5-HTT and 5-HT1A binding could improve prediction of post-treatment remission status. Methods: 31 healthy controls (Hamilton Depression Rating Scale-24 item (HDRS-24) = 1.7) and 26 medication free patients with MDD (HDRS-24 = 24.76) received a PET scan using 11C-DASB. MDD subjects then received eight weeks of standardized pharmacotherapy with escitalopram. The relationship between pre-treatment binding and post-treatment clinical status was examined. Arterial blood samples were collected to calculate the metabolite-corrected arterial input function. The outcome measure was VT/fP (VT=Volume of Distribution in region of interest (ROI), fP = free fraction in plasma). Remission was defined as a post-treatment depression score of <10 as well as ≥50% reduction in the score from baseline, resulting in 14 non-remitters (HDRS-24 = 17.6) and 12 remitters (HDRS-24 = 5.3). Results: A linear mixed effects model comparing group differences in the a priori ROIs (amygdala and midbrain) revealed a significant difference in amygdala binding between controls and remitters (P = 0.03, unadjusted), where remitters had an 11% lower amygdala binding than controls. Differences in amygdala binding between remitters and non-remitters approached significance (P = 0.06). No additional differences were found between any groups (all p>0.05). Additionally, we found no relationship between pre-treatment amygdala binding and post-treatment depression score, and were unable to predict post-treatment depression severity using both pre-treatment 5-HTT (in the amygdala) and 5-HT1A binding (in the raphe). Conclusion: These results suggest 5-HTT amygdala binding should be examined further, in conjunction with other measures, as a potential biomarker for remission following standardized escitalopram treatment.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28935838

DOI: PubMed:28935838

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