Rapid Neuroplasticity Changes and Response to Intravenous Ketamine: A Randomized Controlled Trial in Treatment-Resistant Depression

Authors

Jared Kopelman
Timothy A Keller
Benjamin Panny
Angela Griffo
Michelle Degutis
Crystal Spotts
Nicolas Cruz
Elizabeth Bell
Kevin Do-Nguyen
Meredith L Wallace
Sanjay J Mathew
Robert H Howland
Rebecca B Price

Language

English

Publication Date

5-9-2023

Journal

Translational Psychiatry

DOI

10.1038/s41398-023-02451-0

PMID

37160885

PMCID

PMC10170140

PubMedCentral® Posted Date

5-9-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Intravenous ketamine is posited to rapidly reverse depression by rapidly enhancing neuroplasticity. In human patients, we quantified gray matter microstructural changes on a rapid (24-h) timescale within key regions where neuroplasticity enhancements post-ketamine have been implicated in animal models. In this study, 98 unipolar depressed adults who failed at least one antidepressant medication were randomized 2:1 to a single infusion of intravenous ketamine (0.5 mg/kg) or vehicle (saline) and completed diffusion tensor imaging (DTI) assessments at pre-infusion baseline and 24-h post-infusion. DTI mean diffusivity (DTI-MD), a putative marker of microstructural neuroplasticity in gray matter, was calculated for 7 regions of interest (left and right BA10, amygdala, and hippocampus; and ventral Anterior Cingulate Cortex) and compared to clinical response measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR). Individual differences in DTI-MD change (greater decrease from baseline to 24-h post-infusion, indicative of more neuroplasticity enhancement) were associated with larger improvements in depression scores across several regions. In the left BA10 and left amygdala, these relationships were driven primarily by the ketamine group (group * DTI-MD interaction effects: p = 0.016-0.082). In the right BA10, these associations generalized to both infusion arms (p = 0.007). In the left and right hippocampus, on the MADRS only, interaction effects were observed in the opposite direction, such that DTI-MD change was inversely associated with depression change in the ketamine arm specifically (group * DTI-MD interaction effects: p = 0.032-0.06). The acute effects of ketamine on depression may be mediated, in part, by acute changes in neuroplasticity quantifiable with DTI.

Keywords

Adult, Animals, Humans, Depression, Diffusion Tensor Imaging, Ketamine, Cerebral Cortex, Neuronal Plasticity, Hippocampus

Published Open-Access

yes

Recommended Citation

Kopelman, Jared; Keller, Timothy A; Panny, Benjamin; et al., "Rapid Neuroplasticity Changes and Response to Intravenous Ketamine: A Randomized Controlled Trial in Treatment-Resistant Depression" (2023). Staff and Researcher Publications. 47.
https://digitalcommons.library.tmc.edu/clinic_pub/47