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Cited by 56Treatment of Major DepressionElectroconvulsive Therapy StudiesTranscranial Magnetic Stimulation Studies

Effects of Ketamine on Brain Activity During Emotional Processing: Differential Findings in Depressed Versus Healthy Control Participants

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Reed, Jessica L., Nugent, Allison C., Furey, Maura L., Szczepanik, Joanna E., Evans, Jennifer W., Zarate, Carlos A.·2019·Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
DOI 10.1016/j.bpsc.2019.01.005PMC PMC6612456
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Abstract

Background In the search for novel treatments for depression, ketamine has emerged as a unique agent with rapid antidepressant effects. Experimental tasks involving emotional processing can be used during functional magnetic resonance imaging scanning to investigate ketamine's effects on brain function in major depressive disorder (MDD). This study examined ketamine's effects on functional magnetic resonance imaging activity during an emotional processing task. Methods A total of 33 individuals with treatment-resistant MDD and 24 healthy control participants (HCs) took part in this double-blind, placebo-controlled crossover study. Participants received ketamine and placebo infusions 2 weeks apart, and functional magnetic resonance imaging scans were conducted at baseline and 2 days after each infusion. Blood oxygen level-dependent signal was measured during an emotional processing task, and a linear mixed-effects model was used to analyze differences in activation among group, drug, and task-specific factors. Results A group-by-drug interaction was observed in several brain regions, including a right frontal cluster extending into the anterior cingulate cortex and insula. Participants with MDD had greater activity than HCs after placebo infusion but showed lower activity after ketamine infusion, which was similar to the activity in HCs after placebo. A group-by-drug-by-task condition interaction was also found, which showed further differences that varied between implicit and explicit emotional conditions. Conclusions The main results indicate that ketamine had differential effects on brain activity in participants with MDD versus HCs. The pattern of activation in participants with MDD after ketamine infusion resembled the activation in HCs after placebo infusion, suggesting a normalization of function during emotional processing. The findings contribute to a better understanding of ketamine's actions in the brain.

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  • In another fMRI study, participants with TRD had lower activity in the right frontal cluster, anterior cingulate cortex, and insula after ketamine infusion when compared to healthy volunteers.

    “participants with TRD had lower activity in the right frontal cluster, anterior cingulate cortex, and insula after ketamine infusion when compared to healthy volunteers”

    From Ketamine in neuropsychiatric disorders: an update (2024) · cites this paper as [212]

  • That pattern mirrored measurements from healthy volunteers after a placebo infusion, suggesting that ketamine normalized function.

    “this pattern mirrored measurements from healthy volunteers after a placebo infusion [212], suggesting that ketamine normalized function.”

    From Ketamine in neuropsychiatric disorders: an update (2024) · cites this paper as [212]

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Authors
Reed, J. L., Nugent, A. C., Furey, M. L., Szczepanik, J. E., Evans, J. W., & Zarate, C. A.
Affiliations
National Institutes of Health (US)
Corresponding author
Reed, Jessica L.
ORCID
Venue
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Publisher
Elsevier BV
Published
2019-07
Volume
4
Issue
7
Pages
610-618
ISSN
2451-9022 (ISSN-L)
DOI
10.1016/j.bpsc.2019.01.005
PMC
PMC6612456
OpenAlex
W2911945569
Cited by
56
References
10
Citations by year
2026: 2 · 2025: 7 · 2024: 12 · 2023: 10 · 2022: 4 · 2021: 7 · 2020: 11 · 2019: 2
FWCI
3.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry Cognitive Neuroscience and Neuroimaging (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health
  • National Institutes of Health (NCT00088699, ZIA MH002857)
  • National Alliance for Research on Schizophrenia and Depression
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
Keywords
ketamine, major depressive disorder, treatment-resistant depression, emotional processing, brain activity, anterior cingulate cortex, insula, frontal cortex, antidepressant effects, functional MRI
MeSH terms
Facial Recognition, Adult, Antidepressive Agents, Brain, Brain Mapping, Major Depressive Disorder, Depressive Disorder, Major, Double-Blind Method, Emotions, Female, Humans, Ketamine, Magnetic Resonance Imaging, Male, Treatment Outcome, Cross-Over Studies

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