ArticleSchizophrenia research2008
Dysregulation of glutamate carboxypeptidase II in psychiatric disease.
Article in Schizophrenia research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- How a Medicinal Chemistry Project Changed the Way Prostate Cancer is Diagnosed and Treated.Journal of medicinal chemistry · 2025Review
- D-DOPA Is a Potent, Orally Bioavailable, Allosteric Inhibitor of Glutamate Carboxypeptidase II.Pharmaceutics · 2022Article
- Molecular linkage between post-traumatic stress disorder and cognitive impairment: a targeted proteomics study of World Trade Center responders.Translational psychiatry · 2020Article
- The therapeutic and diagnostic potential of the prostate specific membrane antigen/glutamate carboxypeptidase II (PSMA/GCPII) in cancer and neurological disease.British journal of pharmacology · 2016Review
- Article
- Synthesis and Biological Evaluation of Substrate-Based Imaging Agents for the Prostate-Specific Membrane Antigen.Macromolecular research · 2013Article
- N-acetylaspartylglutamate (NAAG) and N-acetylaspartate (NAA) in patients with schizophrenia.Schizophrenia bulletin · 2013Article
- Glutamate carboxypeptidase II and folate deficiencies result in reciprocal protection against cognitive and social deficits in mice: implications for neurodevelopmental disorders.Developmental neurobiology · 2012Article
- NAAG, NMDA receptor and psychosis.Current medicinal chemistry · 2012Review
- Glutamatergic synaptic dysregulation in schizophrenia: therapeutic implications.Handbook of experimental pharmacology · 2012Review
- Glutamate carboxypeptidase II in diagnosis and treatment of neurologic disorders and prostate cancer.Current medicinal chemistry · 2012Review
- Novel substrate-based inhibitors of human glutamate carboxypeptidase II with enhanced lipophilicity.Journal of medicinal chemistry · 2011Article
- The folate hydrolase 1561C>T polymorphism is associated with depressive symptoms in Puerto Rican adults.Psychosomatic medicine · 2011Article
- The neuropeptide VGF is reduced in human bipolar postmortem brain and contributes to some of the behavioral and molecular effects of lithium.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
- Bioisosterism of urea-based GCPII inhibitors: Synthesis and structure-activity relationship studies.Bioorganic & medicinal chemistry letters · 2010Article
- The role of the tripartite glutamatergic synapse in the pathophysiology and therapeutics of mood disorders.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2009Review
- Phenotypic characterization of mice heterozygous for a null mutation of glutamate carboxypeptidase II.Synapse (New York, N.Y.) · 2009Article
- Differential expression of metabotropic glutamate receptors 2 and 3 in schizophrenia: a mechanism for antipsychotic drug action?The American journal of psychiatry · 2009Article
- Localization of NAAG-related gene expression deficits to the anterior hippocampus in schizophrenia.Schizophrenia research · 2009Article
- Interactions between human glutamate carboxypeptidase II and urea-based inhibitors: structural characterization.Journal of medicinal chemistry · 2008Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Experimental evidence is beginning to converge on an important role for dysregulation of glutamate carboxypeptidase II (GCPII) in schizophrenia. The goal of this study was to determine GCPII levels in postmortem brain specimens of patients with schizophrenia, bipolar disorder or unipolar depression and age-matched control subjects. We used N-[N-(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-[(125)I]iodo-l-tyrosine ([(125)I]DCIT), a high-affinity radioligand for GCPII, to probe for GCPII expression in prefrontal cortex (PFC) and mesial temporal lobe, two brain regions implicated in the pathophysiology of schizophrenia. We found that GCPII levels measured by [(125)I]DCIT quantitative autoradiography were significantly lower in the PFC and entorhinal cortex in patients with schizophrenia compared to age-matched controls. Patients with bipolar disorder also expressed significantly lower GCPII levels in PFC than controls. The decrease in [(125)I]DCIT binding in schizophrenia and bipolar disorder remained significant after adjusting for drug abuse. A significant difference in GCPII levels was also observed between schizophrenia relative to bipolar disorder and depressed subjects in the hippocampus-stratum lucidum and between schizophrenia and bipolar in the CA2 region of the hippocampus, with bipolar and depressed subjects expressing higher levels of GCPII than subjects with schizophrenia. These differences in hippocampal GCPII levels may implicate differences in the etiologies of these mental disorders. In summary, this study demonstrates a regional dysregulation of GCPII expression in the brain of patients with schizophrenia and other psychiatric disorders and supports a hypoglutamatergic state of the former illness. GCPII may represent a viable therapeutic target for intervention in psychiatric disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.