Cited by 168Neuroscience and Neuropharmacology ResearchTreatment of Major DepressionAmino Acid Enzymes and Metabolism

Translating Glutamate: From Pathophysiology to Treatment

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Javitt, Daniel C., Schoepp, Darryle, Kalivas, Peter W., Volkow, Nora D., Zarate, Carlos, Merchant, Kalpana, Bear, Mark F., Umbricht, Daniel +3 more·2011·Science Translational Medicine

Abstract

On 21 to 22 June 2010, the Institute of Medicine Forum on Neuroscience and Nervous System Disorders, Board on Health Sciences Policy, discussed the role of glutamate in neuropsychiatric disease at the meeting “Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System.”

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  • Treatment of adult rodents with NMDAR antagonists triggers acute schizophrenia-related behaviours, including deficits in attention/vigilance, learning and memory, and sensory gating.

    “As in humans, treatment of adult rodents with NMDAR antagonists triggers acute schizophrenia-related behaviours, including deficits in attention and/ or vigilance, learning and memory and sensory gating, broadly mimicking the symptoms of patients with schizophrenia 10,15,23,24 .”
  • Behavioral, neurophysiological and functional imaging studies show that indicators of sensory dysfunction in patients with schizophrenia can be mimicked by treating healthy individuals with NMDAR antagonists.

    “Subsequent behavioral, neurophysiological and functional imaging studies have supported the NMDAR hypofunction hypothesis of schizophrenia, showing that indicators of sensory dysfunction in patients with schizophrenia -such as mismatch negativity (MMN) and changes in auditory and visual event-related potentials -can be mimicked by treating otherwise healthy individuals with NMDAR antagonists 12,15”

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Authors
Javitt, D. C., Schoepp, D., Kalivas, P. W., Volkow, N. D., Zarate, C., Merchant, K., Bear, M. F., Umbricht, D., Hajos, M., Potter, W. Z., & Lee, C.-M.
Affiliations
  • Columbia University (US)
  • Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
  • Medical University of South Carolina (US)
  • National Institute on Drug Abuse (US)
  • National Institutes of Health (US)
  • Eli Lilly (United States) (US)
  • Massachusetts Institute of Technology (US)
  • F. Hoffmann-La Roche AG (CH)
  • Neuroscience Department, CNS Discovery, Pfizer Global Research and Development, Groton, CT 06340, USA.
  • Foundation for the National Institutes of Health (US)
  • AstraZeneca (Sweden) (SE)
Corresponding author
Javitt, Daniel C.
Venue
Science Translational Medicine
Published
2011-09-28
Volume
3
Issue
102
Pages
102mr2-102mr2
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
OpenAlex
W1559706924
Cited by
168
References
150
Citations by year
2026: 1 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 12 · 2020: 11 · 2019: 14 · 2018: 10 · 2017: 10 · 2016: 5 · 2015: 19 · 2014: 19 · 2013: 19 · 2012: 22
Type
conference abstract
Language
en
Open access
Locations
  • Science Translational Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (R37MH049334, R37MH49334, P50MH086385, ZIAMH002857)
  • National Institute on Drug Abuse (R01DA03383, R01DA003383)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD046943)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
glutamate, glutamatergic neurotransmission, neuropsychiatric disorders, schizophrenia, drug addiction, autism spectrum disorder, depression, biomarkers, translational model, drug development, target engagement
MeSH terms
Animals, Clinical Trials as Topic, Congresses as Topic, Humans, Nervous System Diseases, Neurotransmitter Agents, Glutamic Acid, Mice, Translational Research, Biomedical

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