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 Lener, Lawrence Park, Dawn F. Ionescu, Elizabeth D. Ballard, Nancy E. Brutsche, Nirmala Akula, Francis J. McMahon, Rodrigo Machado-Vieira, Allison C. Nugent, Carlos A. Zarate

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1570-1577
Number of pages8
JournalJournal of Psychopharmacology
Volume31
Issue number12
DOIs
StatePublished - Dec 1 2017

Keywords

  • brain-derived neurotrophic factor (BDNF)
  • ketamine
  • Major depressive disorder
  • thalamus
  • val66met

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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    Niciu, M. J., Iadarola, N. D., Banerjee, D., Luckenbaugh, D. A., Park, M., Lener, M., Park, L., Ionescu, D. F., Ballard, E. D., Brutsche, N. E., Akula, N., McMahon, F. J., Machado-Vieira, R., Nugent, A. C., & Zarate, C. A. (2017). The antidepressant efficacy of subanesthetic-dose ketamine does not correlate with baseline subcortical volumes in a replication sample with major depressive disorder. Journal of Psychopharmacology, 31(12), 1570-1577. https://doi.org/10.1177/0269881117732514