Abstract
Background:
This study sought to reproduce, in a larger sample, previous findings of a correlation between smaller raw 3-Tesla (3T) hippocampal volumes and improved antidepressant efficacy of ketamine in individuals with major depressive disorder (MDD). A secondary analysis stratified subjects according to functional BDNF rs6265 (val66met) genotype.
Methods:
Unmedicated subjects with treatment-resistant MDD (n=55) underwent baseline structural 3T MRI. Data processing was conducted with FSL/FIRST and Freesurfer software. The amygdala, hippocampus, and thalamus were selected a priori for analysis. All subjects received a single 0.5mg/kg × 40-minute ketamine infusion. Pearson correlations were performed with subcortical volumes and percent change in MADRS score (from baseline to 230 minutes, 1 day, and 1 week post-infusion).
Results:
Raw and corrected subcortical volumes did not correlate with antidepressant response at any timepoint. In val/val subjects (n=23), corrected left and right thalamic volume positively correlated with antidepressant response to ketamine at 230 minutes post-infusion but did not reach statistical significance. In met carriers (n=14), corrected left and right thalamic volume negatively correlated with antidepressant response to ketamine.
Conclusion:
Baseline subcortical volumes implicated in MDD did not correlate with ketamine’s antidepressant efficacy. Baseline thalamic volume and BDNF genotype may be a combinatorial rapid antidepressant response biomarker.
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Supplementary Material
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