The antidepressant efficacy of subanesthetic-dose ketamine does not correlate with baseline subcortical volumes in a replication sample with major depressive disorder. (December 2017)

• Record Type: Journal Article
• Authors: Niciu, Mark J; Iadarola, Nicolas D; Banerjee, Dipavo; Luckenbaugh, David A; Park, Minkyung; Lener, Marc; Park, Lawrence; Ionescu, Dawn F; Ballard, Elizabeth D; Brutsche, Nancy E; Akula, Nirmala; McMahon, Francis J; Machado-Vieira, Rodrigo; Nugent, Allison C; Zarate, Carlos A
• Is Part Of: Journal of psychopharmacology. Volume 31:Number 12(2017)
• Page Start: 1570
• Page End: 1577
• Publication Date: 2017-12
• Subjects: Major depressive disorder -- ketamine -- thalamus -- brain-derived neurotrophic factor (BDNF) -- val66met; Psychopharmacology -- Periodicals; 615.78
• DOI: 10.1177/0269881117732514
• Languages: English
• ISSNs: 0269-8811

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.