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 Jr

doi:10.1177/0269881117732514

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

Journal article

Open access

Peer reviewed

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, …

Journal of psychopharmacology (Oxford), Vol.31(12), pp.1570-1577

12/2017

DOI: 10.1177/0269881117732514

PMCID: PMC5863225

PMID: 29039254

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https://www.ncbi.nlm.nih.gov/pmc/articles/5863225View

Open Access

Abstract

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. 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). 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. 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.

Neuroimaging

Magnetic Resonance Imaging

Brain-Derived Neurotrophic Factor - genetics

Humans

Middle Aged

Atrophy - pathology

Male

Thalamus - pathology

Young Adult

Adult

Female

Ketamine - therapeutic use

Depressive Disorder, Major - drug therapy

Depressive Disorder, Major - pathology

Double-Blind Method

Depressive Disorder, Treatment-Resistant - pathology

Genotype

Treatment Outcome

Hippocampus - pathology

Depressive Disorder, Treatment-Resistant - drug therapy

Amygdala - pathology

Antidepressive Agents - therapeutic use

Depressive Disorder, Major - genetics

Adolescent

Aged

Details

Title: Subtitle: The antidepressant efficacy of subanesthetic-dose ketamine does not correlate with baseline subcortical volumes in a replication sample with major depressive disorder
Creators: Mark J Niciu - 1 Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Nicolas D Iadarola - 1 Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Dipavo Banerjee - 1 Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
David A Luckenbaugh - 1 Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Minkyung Park - 1 Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Marc Lener - 1 Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Lawrence Park - 1 Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Dawn F Ionescu - 2 Depression Clinical and Research Program, Massachusetts General Hospital, Boston, USA
Elizabeth D Ballard - 1 Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Nancy E Brutsche - 1 Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Nirmala Akula - 3 Human Genetics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Francis J McMahon - 3 Human Genetics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Rodrigo Machado-Vieira - 1 Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Allison C Nugent - 1 Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Carlos A Zarate Jr - 1 Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Resource Type: Journal article
Publication Details: Journal of psychopharmacology (Oxford), Vol.31(12), pp.1570-1577
DOI: 10.1177/0269881117732514
PMID: 29039254
PMCID: PMC5863225
NLM abbreviation: J Psychopharmacol
ISSN: 0269-8811
eISSN: 1461-7285
Publisher: United States
Grant note: ZIA MH002857-12 / Intramural NIH HHS UL1 TR000371 / NCATS NIH HHS
Language: English
Date published: 12/2017
Academic Unit: Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984003488602771

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