Default Mode Connectivity in Major Depressive Disorder Measured Up to 10 Days After Ketamine Administration
Open accessAbstract
Background 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).Methods 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.Results 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.Conclusions 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.
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Increased connectivity between the default mode network (DMN) and the insula has been reported in depressed patients 2 days following ketamine.
“Increased connectivity between the default mode network (DMN), which encompasses the medial PFC, and the insula have also been reported in depressed patients 2 days following ketamine, suggesting sustained normalization of the DMN's relationship to other networks 129 .”
From Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model (2020) · cites this paper as [129]
Experimental — accuracy not yet measuredKetamine administration in depressed patients appears to reconfigure functional connectivity within the DMN.
“Ketamine administration in depressed patients also appears to reconfigure functional connectivity within the DMN.”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [89]
Normalization of insular DMN hyperactivity in TRD patients appears to coincide with peak antidepressant responses (48 h), subsequently reversing at 10 days post-infusion.
“Notably, normalization of insular DMN hyperactivity in TRD patients appears to coincide with peak antidepressant responses (48 h), subsequently reversing at 10 days post-infusion (when effects on mood are typically lost) [89].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [89]
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- Authors
- Evans, J. W., Szczepanik, J., Brutsché, N., Park, L. T., Nugent, A. C., & Zarate, C. A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Evans, Jennifer W.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 84
- Issue
- 8
- Pages
- 582-590
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC6093808
- OpenAlex
- W2791671940
- Cited by
- 173
- References
- 54
- Citations by year
- 2026: 21 · 2025: 15 · 2024: 16 · 2023: 23 · 2022: 19 · 2021: 20 · 2020: 32 · 2019: 20 · 2018: 7
- FWCI
- 12.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 MH999999)
- National Institute of Mental Health (Z01MH002857)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- major depressive disorder, ketamine, default mode network, resting-state functional connectivity, insula, salience network, thalamus, seed-based correlation
- MeSH terms
- Adolescent, Adult, Aged, Antidepressive Agents, Brain Mapping, Cerebral Cortex, Major Depressive Disorder, Double-Blind Method, Female, Humans, Infusions, Intravenous, Ketamine, Magnetic Resonance Imaging, Male, Middle Aged, Cross-Over Studies, Young Adult
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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