The antidepressant efficacy of subanesthetic-dose ketamine does not correlate with baseline subcortical volumes in a replication sample with major depressive disorder
Mark J. Niciu, Nicolas D. Iadarola, Dipavo Banerjee, David A. Luckenbaugh, Minkyung Park, Marc S. Lener, Lawrence T. Park, Dawn F. Ionescu, Elizabeth D. Ballard, Nancy E. Brutsché, Nirmala Akula, Francis J. McMahon, Rodrigo Machado‐Vieira, Allison C. Nugent, Carlos A. Zarate
Journal of Psychopharmacology October 17, 2017 DOI: 10.1177/0269881117732514 (opens in new tab) via OpenAlex
Summary
AI-generated from the abstractIn a sample of 55 unmedicated individuals with treatment-resistant major depressive disorder, baseline volumes of the hippocampus, amygdala, and thalamus measured with 3-Tesla MRI did not correlate with the antidepressant effect of a single 0.5 mg/kg ketamine infusion at any time point (230 minutes, 1 day, or 1 week). A secondary analysis by BDNF rs6265 genotype suggested that in val/val homozygotes, larger thalamic volume was positively associated with response at 230 minutes, while in met carriers, larger thalamic volume was negatively associated, though these correlations did not reach statistical significance. The authors conclude that baseline thalamic volume combined with BDNF genotype may serve as a rapid antidepressant response biomarker.
Study at a glance
| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 55 |
| Population | Unmedicated individuals with treatment-resistant major depressive disorder |
| Intervention | Ketamine infusion |
| Dose | 0.5 mg/kg |
| Duration | Single 40-minute infusion with follow-up at 230 minutes, 1 day, and 1 week |
| Topics | Depression Ketamine |
| Keywords | Antidepressant Psychology Anesthesia |
| Citations | 23 |
| Key finding | Baseline subcortical volumes did not correlate with ketamine's antidepressant efficacy, but thalamic volume and BDNF genotype may together predict rapid response. |
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.