Default Mode Connectivity in Major Depressive Disorder Measured Up to 10 Days After Ketamine Administration.
Jennifer W. Evans, Joanna E Szczepanik, Nancy E. Brutsché, Lawrence T. Park, Allison C. Nugent, Carlos A. Zarate
Biological Psychiatry October 15, 2018 DOI: 10.1016/j.biopsych.2018.01.027 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled crossover study Peer reviewed |
|---|---|
| Sample size | 58 |
| Population | Unmedicated subjects with major depressive disorder (n=33) and healthy control subjects (n=25) |
| Interventions | Ketamine hydrochloride placebo |
| Dose | 0.5 mg/kg |
| Duration | Scans at baseline and about 2 and 10 days after each infusion; test days spaced 2 weeks apart |
| Measures | seed-based correlation (resting-state functional magnetic resonance imaging) |
| Topics | Default mode network Depression Ketamine Esketamine |
| Keywords | Glutamatergic modulator Resting state |
| Key points | In subjects with MDD, insula-default mode network connectivity was normalized compared with healthy controls 2 days after ketamine infusion, reversed by 10 days, and absent in placebo scans. Drug-response connectivity differences were group-specific, notably in the insula in MDD and the thalamus in healthy controls. The authors suggest these changes indicate ketamine may normalize default mode-salience network interaction, supporting the triple network dysfunction model of MDD. |
Abstract
The symptoms of major depressive disorder (MDD) are rapidly alleviated by administration of a single dose of the glutamatergic modulator ketamine. However, few studies have investigated the potential sustained neural effects of this agent beyond immediate infusion. This study used functional magnetic resonance imaging to examine the effect of a single ketamine infusion on the resting state default mode network (DMN) at 2 and 10 days after a single ketamine infusion in unmedicated subjects with MDD as well as healthy control subjects (HCs). Data were drawn from a double-blind, placebo-controlled crossover study of 58 participants (33 with MDD and 25 HCs) who received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 separate test days spaced 2 weeks apart. Eight minutes of functional magnetic resonance imaging resting state data was acquired at baseline and at about 2 and 10 days after both infusions. The DMN was defined using seed-based correlation and was compared across groups and scans. In subjects with MDD, connectivity between the insula and the DMN was normalized compared with HCs 2 days postketamine infusion. This change was reversed after 10 days and did not appear in either of the placebo scans. Group-specific connectivity differences in drug response were observed, most notably in the insula in subjects with MDD and in the thalamus in HCs. Connectivity changes in the insula in subjects with MDD suggest that ketamine may normalize the interaction between the DMN and salience networks, supporting the triple network dysfunction model of MDD.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.
Citations in the library
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- Psychedelic drugs—a new era in psychiatry? Dialogues in Clinical Neuroscience June 30, 2019
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Cites 10
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Ketamine: 50 Years of Modulating the Mind Frontiers in Human Neuroscience November 29, 2016
- Glutamate and the Neural Basis of the Subjective Effects of Ketamine Archives of General Psychiatry February 1, 2008
- Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action PLoS One September 24, 2012
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