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Cited by 168Treatment of Major DepressionElectroconvulsive Therapy StudiesTryptophan and brain disorders

Neural Correlates of Rapid Antidepressant Response to Ketamine in Treatment-Resistant Unipolar Depression: A Preliminary Positron Emission Tomography Study

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Carlson, Paul J., Diazgranados, Nancy, Nugent, Allison C., Ibrahim, Lobna, Luckenbaugh, David A., Brutsche, Nancy, Herscovitch, Peter, Manji, Husseini K. +2 more·2013·Biological Psychiatry
DOI 10.1016/j.biopsych.2013.02.008PMC PMC3672258
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Abstract

Background Multiple lines of evidence support a role for the glutamatergic system in the pathophysiology of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate antagonist, rapidly improves depressive symptoms in individuals with treatment-resistant depression. The neural mechanisms underlying this effect remain unknown. Methods In this preliminary study, 20 unmedicated participants with treatment-resistant MDD underwent positron emission tomography to measure regional cerebral glucose metabolism at baseline and following ketamine infusion (single dose of .5mg/kg intravenous over 40minutes). Metabolic data were compared between conditions using a combination of region-of-interest and voxelwise analyses, and differences were correlated with the associated antidepressant response. Results Whole-brain metabolism did not change significantly following ketamine. Regional metabolism decreased significantly under ketamine in the habenula, insula, and ventrolateral and dorsolateral prefrontal cortices of the right hemisphere. Metabolism increased postketamine in bilateral occipital, right sensorimotor, left parahippocampal, and left inferior parietal cortices. Improvement in depression ratings correlated directly with change in metabolism in right superior and middle temporal gyri. Conversely, clinical improvement correlated inversely with metabolic changes in right parahippocampal gyrus and temporoparietal cortex. Conclusions Although preliminary, these results indicate that treatment-resistant MDD subjects showed decreased metabolism in the right habenula and the extended medial and orbital prefrontal networks in association with rapid antidepressant response to ketamine. Conversely, metabolism increased in sensory association cortices, conceivably related to the illusory phenomena sometimes experienced with ketamine. Further studies are needed to elucidate how these functional anatomical changes relate to the molecular mechanisms underlying ketamine's rapid antidepressant effects.

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  • Antidepressant effects of low-dose ketamine and transcranial magnetic stimulation can improve cerebral glucose metabolism in these regions.

    “Antidepressant effects of low-dose ketamine [56] and transcranial magnetic stimulation can improve the cerebral glucose metabolism in these regions [57–60].”

    From APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline (2021) · cites this paper as [57]

    The Results (page unavailable) report that low-dose ketamine changed regional glucose metabolism in participants with treatment-resistant depression, with increases in some regions and decreases in others; whole-brain metabolism did not change significantly. The source therefore supports a regional metabolic effect, but not a general claim that ketamine improved metabolism in the unspecified ‘these regions.’ Transcranial magnetic stimulation is cited to other sources in the sentence and is not assessed here. (LLM, conf=0.86)

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Authors
Carlson, P. J., Diazgranados, N., Nugent, A. C., Ibrahim, L., Luckenbaugh, D. A., Brutsche, N., Herscovitch, P., Manji, H. K., Zarate, C. A., & Drevets, W. C.
Affiliations
  • VA Salt Lake City Healthcare System (US)
  • The University of Texas at San Antonio Health Science Center (US)
  • National Institutes of Health (US)
  • Laureate Institute for Brain Research (US)
Corresponding author
Zarate, Carlos A.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2013-06
Volume
73
Issue
12
Pages
1213-1221
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2013.02.008
PMC
PMC3672258
OpenAlex
W2048046359
Cited by
168
References
18
Citations by year
2026: 7 · 2025: 9 · 2024: 7 · 2023: 7 · 2022: 18 · 2021: 11 · 2020: 18 · 2019: 12 · 2018: 12 · 2017: 8 · 2016: 19 · 2015: 18 · 2014: 15 · 2013: 6
FWCI
12.83
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (ZIAMH002857, ZIAMH002927)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
ketamine, treatment-resistant depression, major depressive disorder, rapid antidepressant response, glutamatergic system, NMDA receptor antagonists, brain glucose metabolism, habenula, prefrontal cortex, parahippocampal gyrus, temporal cortex
MeSH terms
Adult, Antidepressive Agents, Brain, Brain Mapping, Female, Humans, Image Processing, Computer-Assisted, Ketamine, Magnetic Resonance Imaging, Male, Middle Aged, Oxygen, Fluorodeoxyglucose F18, Positron-Emission Tomography, Depressive Disorder, Treatment-Resistant

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