Cited by 208Schizophrenia research and treatmentAmino Acid Enzymes and MetabolismNeuroscience and Neuropharmacology Research

The NMDA receptor ‘glycine modulatory site’ in schizophrenia: d-serine, glycine, and beyond

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Balu, Darrick T, Coyle, Joseph T·2015·Current Opinion in Pharmacology

Abstract

Schizophrenia is a severe psychiatric illness that is characterized by reduced cortical connectivity, for which the underlying biological and genetic causes are not well understood. Although the currently approved antipsychotic drug treatments, which primarily modulate dopaminergic function, are effective at reducing positive symptoms (i.e. delusions and hallucinations), they do little to improve the disabling cognitive and negative (i.e. anhedonia) symptoms of patients with schizophrenia. This review details the recent genetic and neurobiological findings that link N-methyl-D-aspartate receptor (NMDAR) hypofunction to the etiology of schizophrenia. It also highlights potential treatment strategies that augment NMDA receptor function to treat the synaptic deficits and cognitive impairments.

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  • Genetic evidence points to disturbed NMDAR signaling in schizophrenia: a GWAS implicated SRR and GRIN2A as risk genes and other genes functionally up- and downstream of NMDAR activity.

    “A recent genome-wide association study (GWAS) implicated serine racemase (SRR) and GRIN2A as risk genes for schizophrenia 21 as well as other genes functionally up-and downstream of NMDAR activity 21,22 .”

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Authors
Balu, D. T., & Coyle, J. T.
Affiliations
Harvard University (US)
Corresponding author
Coyle, Joseph T
Venue
Current Opinion in Pharmacology
Publisher
Elsevier BV
Published
2015-02
Volume
20
Pages
109-115
ISSN
1471-4892 (ISSN-L)
OpenAlex
W1996473902
Cited by
208
References
63
Citations by year
2026: 10 · 2025: 13 · 2024: 11 · 2023: 13 · 2022: 5 · 2021: 23 · 2020: 19 · 2019: 13 · 2018: 24 · 2017: 39 · 2016: 21 · 2015: 17
FWCI
3.55
Type
journal article
Language
en
Open access
Locations
  • Current Opinion in Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (P50MH060450, R01MH051290, R01MH05190, P50MH0G0450, K99MH099252)
  • National Institute on Drug Abuse (R21DA035427)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
schizophrenia, NMDA receptor, D-serine, glycine, NMDA receptor hypofunction, cortical connectivity, cognitive impairment, negative symptoms, synaptic deficits, genetic etiology
MeSH terms
Animals, Cognition Disorders, Dopamine, Glycine, Humans, Schizophrenia, Serine, Synapses, Antipsychotic Agents, Receptors, N-Methyl-D-Aspartate

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