The glutamate hypothesis of schizophrenia: evidence from human brain tissue studies

Hu, Wei; MacDonald, Matthew L.; Elswick, Daniel E.; Sweet, Robert A.

doi:10.1111/nyas.12547

Cited by 286Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchAmino Acid Enzymes and Metabolism

The glutamate hypothesis of schizophrenia: evidence from human brain tissue studies

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Hu, Wei, MacDonald, Matthew L., Elswick, Daniel E., Sweet, Robert A.·2015·Annals of the New York Academy of Sciences

DOI 10.1111/nyas.12547PMC PMC4363164

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Abstract

A number of studies have indicated that antagonists of the N ‐methyl‐ d ‐aspartate subtypes of glutamate receptors can cause schizophrenia‐like symptoms in healthy individuals and exacerbate symptoms in individuals with schizophrenia. These findings have led to the glutamate hypothesis of schizophrenia. Here we review the evidence for this hypothesis in postmortem studies of brain tissue from individuals affected by schizophrenia, summarizing studies of glutamate neuron morphology, of expression of glutamate receptors and transporters, and of the synthesizing and metabolizing enzymes for glutamate and its co‐agonists. We found consistent evidence of morphological alterations of dendrites of glutamatergic neurons in the cerebral cortex of subjects with schizophrenia and of reduced levels of the axon bouton marker synaptophysin. There were no consistent alterations of mRNA expression of glutamate receptors, although there has been limited study of the corresponding proteins. Studies of the glutamate metabolic pathway have been limited, although there is some evidence that excitatory amino acid transporter‐2, glutamine synthetase, and glutaminase have altered expression in schizophrenia. Future studies would benefit from additional direct examination of glutamatergic proteins. Further advances, such as selective testing of synaptic microdomains, cortical layers, and neuronal subtypes, may also be required to elucidate the nature of glutamate signaling impairments in schizophrenia.

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De novo mutations are enriched in the 244 genes with case-control P<0.01, with limited or no signal in remaining genes.
“Using Poisson rate tests based on expected mutation rate27, we found these de novo mutations are enriched for the 244 genes with P < 0.01 in our case-control analysis (Figure S13, Table S5), with limited or no signal in the remaining genes in the genome (Figure 1D).”
From Rare coding variants in ten genes confer substantial risk for schizophrenia (2022) · cites this paper as [27]

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RETRACTED: Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in the postmortem frontal cortex from schizophrenia patients
Rao, J. S., Kim, H.-W., Harry, G. J., Rapoport, S. I., & Reese, E. A. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2013.02.017 · Cited by 106 · see citing works
Retracted
RETRACTED: Dysregulated glutamate and dopamine transporters in postmortem frontal cortex from bipolar and schizophrenic patients
Rao, J. S., Kellom, M., Reese, E. A., Rapoport, S. I., & Kim, H. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.08.017 · Cited by 101 · see citing works
Retracted
Biological insights from 108 schizophrenia-associated genetic loci
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) · Nature · doi:10.1038/nature13595 · Cited by 7,577 · see citing works
Insights into the regulation of protein abundance from proteomic and transcriptomic analyses
Vogel, C., & Marcotte, E. M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3185 · Cited by 4,195 · see citing works
Glutamate uptake
Danbolt, N. C. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00067-8 · Cited by 4,068 · see citing works
Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies
Dalmau, J., Gleichman, A. J., Hughes, E. G., Rossi, J. E., Peng, X., Lai, M., Dessain, S. K., Rosenfeld, M. R., Balice-Gordon, R., & Lynch, D. R. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70224-2 · Cited by 3,488 · see citing works
Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans: Psychotomimetic, Perceptual, Cognitive, and Neuroendocrine Responses
Krystal, J. H. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950030035004 · Cited by 3,330 · see citing works
Recent advances in the phencyclidine model of schizophrenia
(1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.10.1301 · Cited by 2,904 · see citing works
Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence
Harrison, P. J., & Weinberger, D. R. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001558 · Cited by 2,020 · see citing works
Glutamate receptor dysfunction and schizophrenia
Olney, J. W. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950240016004 · Cited by 1,685 · see citing works
Decreased Dendritic Spine Density on Prefrontal Cortical Pyramidal Neurons in Schizophrenia
Glantz, L. A., & Lewis, D. A. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.1.65 · Cited by 1,636 · see citing works
De novo mutations in schizophrenia implicate synaptic networks
Fromer, M., Pocklington, A. J., Kavanagh, D. H., Williams, H. J., Dwyer, S., Gormley, P., Georgieva, L., Rees, E., Palta, P., Ruderfer, D. M., et al. (2014) · Nature · doi:10.1038/nature12929 · Cited by 1,617 · see citing works
Genome-wide association analysis identifies 13 new risk loci for schizophrenia
Multicenter Genetic Studies of Schizophrenia Consortium, Ripke, S., Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium 2, O'Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., Bergen, S. E., et al. (2013) · Nature Genetics · doi:10.1038/ng.2742 · Cited by 1,496 · see citing works
Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesicles
Wiedenmann, B. J., & Franke, W. W. (1985) · Cell · doi:10.1016/s0092-8674(85)80082-9 · Cited by 1,432 · see citing works
A polygenic burden of rare disruptive mutations in schizophrenia
Purcell, S. M., Moran, J. L., Fromer, M., Ruderfer, D., Solovieff, N., Roussos, P., O’Dushlaine, C., Chambert, K., Bergen, S. E., Kähler, A., et al. (2014) · Nature · doi:10.1038/nature12975 · Cited by 1,385 · see citing works
The Expression of Vesicular Glutamate Transporters Defines Two Classes of Excitatory Synapse
Fremeau, R. T., Troyer, M. D., Pahner, I., Nygaard, G. O., Tran, C. H., Reimer, R. J., Bellocchio, E. E., Fortin, D. L., Storm‐Mathisen, J., & Edwards, R. H. (2001) · Neuron · doi:10.1016/s0896-6273(01)00344-0 · Cited by 1,266 · see citing works
Rapid Dendritic Morphogenesis in CA1 Hippocampal Dendrites Induced by Synaptic Activity
Maletić‐Savatić, M., Malinow, R., & Svoboda, K. (1999) · Science · doi:10.1126/science.283.5409.1923 · Cited by 1,189 · see citing works
D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor.
Mothet, J., Parent, A., Wolosker, H., Brady, R., Linden, D. J., Ferris, C., Rogawski, M., & Snyder, S. (2000) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.97.9.4926 · Cited by 1,164 · see citing works
Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis
Hughes, E. G., Peng, X., Gleichman, A. J., Lai, M., Zhou, L., Tsou, R., Parsons, T. D., Lynch, D. R., Dalmau, J., & Balice-Gordon, R. J. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0167-10.2010 · Cited by 1,143 · see citing works
Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress
Prabakaran, S., SWATTON, J. E., Ryan, M. M., Huffaker, S. J., Huang, J.-J., Griffin, J. L., Wayland, M. T., Freeman, T., Dudbridge, F., Lilley, K. S., et al. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001511 · Cited by 973 · see citing works
Neuropharmacology of quinolinic and kynurenic acids.
Stone, T. W. (1993) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)00441-7 · Cited by 949 · see citing works
A 38,000-dalton membrane protein (p38) present in synaptic vesicles.
Jahn, R., SCHIEBLER, W., Ouimet, C. C., & Greengard, P. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4137 · Cited by 851 · see citing works
D-serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release
Schell, M. J., Molliver, M. E., & Snyder, S. H. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.9.3948 · Cited by 832 · see citing works
Serine racemase: A glial enzyme synthesizing <scp>d</scp> -serine to regulate glutamate- <i>N</i> -methyl- <scp>d</scp> -aspartate neurotransmission
Wolosker, H., Blackshaw, S., & Snyder, S. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.23.13409 · Cited by 811 · see citing works
Identification of a serotonin/glutamate receptor complex implicated in psychosis
González-Maeso, J., Ang, R. L., Yuen, T., Chan, P., Weisstaub, N. V., López-Giménez, J. F., Zhou, M., Okawa, Y., Callado, L. F., Milligan, G., et al. (2008) · Nature · doi:10.1038/nature06612 · Cited by 803 · see citing works
VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate
Fremeau, R. T., Voglmaier, S., Seal, R. P., & Edwards, R. H. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2003.11.005 · Cited by 745 · see citing works
Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia
Garey, L. J., Ong, W., Patel, T. S., Kanani, M., Davis, A., Mortimer, A. M., Barnes, T., & Hirsch, S. R. (1998) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.65.4.446 · Cited by 719 · see citing works
Unveiling the Functions of Presynaptic Metabotropic Glutamate Receptors in the Central Nervous System
Schoepp, D. D. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29296-x · Cited by 693 · see citing works
Ketamine-Induced Exacerbation of Psychotic Symptoms and Cognitive Impairment in Neuroleptic-Free Schizophrenics
Malhotra, A. K. (1997) · Neuropsychopharmacology · doi:10.1016/s0893-133x(97)00036-5 · Cited by 681 · see citing works
Protein p38: an integral membrane protein specific for small vesicles of neurons and neuroendocrine cells.
Navone, F., Jahn, R., Gioia, G. D., Stukenbrok, H., Greengard, P., & Camilli, P. V. D. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.103.6.2511 · Cited by 674 · see citing works
Synaptic connections between layer 4 spiny neurone-layer 2/3 pyramidal cell pairs in juvenile rat barrel cortex: physiology and anatomy of interlaminar signalling within a cortical column.
Feldmeyer, D., Lübke, J., Silver, R. A., & Sakmann, B. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2001.012959 · Cited by 656 · see citing works
To Model a Psychiatric Disorder in Animals Schizophrenia As a Reality Test
Lipska, B. K. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00137-8 · Cited by 650 · see citing works
A nomenclature for ligand-gated ion channels
Collingridge, G. L., Olsen, R. W., Peters, J. A., & Spedding, M. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.06.063 · Cited by 602 · see citing works
The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention
Sheldon, A. L., & Robinson, M. B. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.03.012 · Cited by 593 · see citing works
Increased cortical kynurenate content in schizophrenia
Schwarcz, R., Rassoulpour, A., Wu, H.-Q., Medoff, D., Tamminga, C. A., & Roberts, R. C. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01078-2 · Cited by 590 · see citing works
Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers
Umbricht, D., Schmid, L., Koller, R., Vollenweider, F. X., Hell, D., & Javitt, D. C. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.12.1139 · Cited by 583 · see citing works
Structural Brain Imaging Evidence for Multiple Pathological Processes at Different Stages of Brain Development in Schizophrenia
Pantelis, C. (2005) · Schizophrenia Bulletin · doi:10.1093/schbul/sbi034 · Cited by 573 · see citing works
The Glutamatergic Dysfunction Hypothesis for Schizophrenia
Coyle, J. T. (1996) · Harvard Review of Psychiatry · doi:10.3109/10673229609017192 · Cited by 568 · see citing works
Mosaic Copy Number Variation in Human Neurons
McConnell, M. J., Lindberg, M. R., Brennand, K. J., Piper, J. C., Voet, T., Cowing-Zitron, C., Shumilina, S., Lasken, R. S., Vermeesch, J. R., Hall, I. M., et al. (2013) · Science · doi:10.1126/science.1243472 · Cited by 551 · see citing works
Neuronal and Glial Somal Size in the Prefrontal Cortex: A Postmortem Morphometric Study of Schizophrenia and Huntington Disease
Rajkowska, G., Selemon, L. D., & Goldman-Rakic, P. S. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.3.215 · Cited by 537 · see citing works
Miniature synaptic events maintain dendritic spines via AMPA receptor activation
McKinney, R. A., Capogna, M., Dürr, R., Gähwiler, B. H., & Thompson, A. S. M. (1999) · Nature Neuroscience · doi:10.1038/4548 · Cited by 523 · see citing works
A Transgenic Alzheimer Rat with Plaques, Tau Pathology, Behavioral Impairment, Oligomeric Aβ, and Frank Neuronal Loss
Cohen, R. M., Rezai-Zadeh, K. P., Weitz, T. M., Rentsendorj, A., Gate, D., Spivak, I. E., Bholat, Y., Vasilevko, V., Glabe, C. G., Breunig, J. J., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3672-12.2013 · Cited by 522 · see citing works
Vesicular Glutamate Transporters 1 and 2 Target to Functionally Distinct Synaptic Release Sites
Fremeau, R. T., Kam, K., Qureshi, T., Johnson, J., Copenhagen, D. R., Storm‐Mathisen, J., Chaudhry, F. A., Nicoll, R. A., & Edwards, R. H. (2004) · Science · doi:10.1126/science.1097468 · Cited by 500 · see citing works
Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia.
Erhardt, S., Blennow, K., Nordin, C., Skogh, E., Lindström, L., & Engberg, G. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(01)02242-x · Cited by 478 · see citing works
Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia
Talbot, K., Eidem, W. L., Tinsley, C. L., Benson, M. A., Thompson, E. W., Smith, R. J., Hahn, C.-G., Siegel, S. J., Trojanowski, J. Q., Gur, R. E., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20425 · Cited by 455 · see citing works
Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics
Akbarian, S., Sucher, N. J., Bradley, D., Tafazzoli, A., Trinh, D., Hetrick, W. P., Potkin, S. G., Sandman, C., Bunney, W. E., & Jones, E. G. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-01-00019.1996 · Cited by 440 · see citing works
Synapses and Alzheimer's Disease
Sheng, M., Sabatini, B. L., & Sudhof, T. C. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005777 · Cited by 436 · see citing works
Synaptic loss in Alzheimer's disease and other dementias
Hamos, J. E., DeGennaro, L. J., & Drachman, D. A. (1989) · Neurology · doi:10.1212/wnl.39.3.355 · Cited by 432 · see citing works
Abnormal Glutamate Receptor Expression in the Medial Temporal Lobe in Schizophrenia and Mood Disorders
Beneyto, M., Kristiansen, L. V., Oni-Orisan, A., McCullumsmith, R. E., & Meador-Woodruff, J. H. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301312 · Cited by 408 · see citing works
Roles and rules of kainate receptors in synaptic transmission
Lerma, J. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1118 · Cited by 373 · see citing works
Kalirin-7 Controls Activity-Dependent Structural and Functional Plasticity of Dendritic Spines
Xie, Z., Srivastava, D. P., Photowala, H., Kai, L., Cahill, M. E., Woolfrey, K. M., Shum, C. Y., Surmeier, D. J., & Penzes, P. (2007) · Neuron · doi:10.1016/j.neuron.2007.10.005 · Cited by 373 · see citing works
Ionotropic Glutamate Receptors and Expression of N-Methyl- d -Aspartate Receptor Subunits in Subregions of Human Hippocampus: Effects of Schizophrenia
Gao, X.-M., Sakai, K., Roberts, R. C., Conley, R. R., Dean, B., & Tamminga, C. A. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.7.1141 · Cited by 371 · see citing works
Presynaptic Regulation of Quantal Size by the Vesicular Glutamate Transporter VGLUT1
Wilson, N. R., Kang, J., Hueske, E. V., Leung, T., Varoqui, H., Murnick, J. G., Erickson, J. D., & Liu, G. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3003-04.2005 · Cited by 335 · see citing works
Reduction of synaptophysin immunoreactivity in the prefrontal cortex of subjects with schizophrenia. Regional and diagnostic specificity.
Glantz, L., & Lewis, D. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830220065010 · Cited by 328 · see citing works
A CSF and postmortem brain study of d-serine metabolic parameters in schizophrenia
Bendikov, I., Nadri, C., Amar, S., Panizzutti, R., DEMIRANDA, J., Wolosker, H., & Agam, G. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2006.10.010 · Cited by 323 · see citing works
Glutamate, Glutamate Receptors, and Downstream Signaling Pathways
Willard, S. S., & Koochekpour, S. (2013) · International Journal of Biological Sciences · doi:10.7150/ijbs.6426 · Cited by 323 · see citing works
Has an Angel Shown the Way? Etiological and Therapeutic Implications of the PCP/NMDA Model of Schizophrenia
Javitt, D. C., Zukin, S. R., Heresco-Levy, U., & Umbricht, D. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs069 · Cited by 322 · see citing works
Impaired Mismatch Negativity Generation Reflects Widespread Dysfunction of Working Memory in Schizophrenia
Javitt, D. C. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950190032005 · Cited by 306 · see citing works
Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer's disease.
Masliah, E., Terry, R. D., Alford, M. F., DeTeresa, R. M., & Hansen, L. A. (1991) · PubMed Central · Cited by 296 · see citing works
Reduced Dendritic Spine Density in Auditory Cortex of Subjects with Schizophrenia
Sweet, R. A., Henteleff, R. A., Zhang, W., Sampson, A. R., & Lewis, D. A. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2008.67 · Cited by 290 · see citing works
Self-citation
Quantitative immunohistochemistry of synaptophysin in human neocortex: an alternative method to estimate density of presynaptic terminals in paraffin sections.
Masliah, E., Terry, R. D., Alford, M. F., & DeTeresa, R. M. (1990) · Journal of Histochemistry & Cytochemistry · doi:10.1177/38.6.2110586 · Cited by 267 · see citing works
Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a Western blot study of synaptophysin, GAP-43 and the complexins
Eastwood, S. L., & Harrison, P. J. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00530-5 · Cited by 262 · see citing works
Decreased Somal Size of Deep Layer 3 Pyramidal Neurons in the Prefrontal Cortex of Subjects With Schizophrenia
Pierri, J. N., Volk, C. L. E., Auh, S., Sampson, A., & Lewis, D. A. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.5.466 · Cited by 257 · see citing works
Lamina-Specific Abnormalities of NMDA Receptor-Associated Postsynaptic Protein Transcripts in the Prefrontal Cortex in Schizophrenia and Bipolar Disorder
Beneyto, M., & Meador‐Woodruff, J. H. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301604 · Cited by 255 · see citing works
Associated deficits in mismatch negativity generation and tone matching in schizophrenia
Javitt, D. C., Shelley, A. M., & Ritter, W. (2000) · Clinical Neurophysiology · doi:10.1016/s1388-2457(00)00377-1 · Cited by 253 · see citing works
Pathology of Layer V Pyramidal Neurons in the Prefrontal Cortex of Patients With Schizophrenia
Black, J. E., Kodish, I. M., Grossman, A. W., Klintsova, A. Y., Orlovskaya, D., Vostrikov, V., Uranova, N., & Greenough, W. T. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.4.742 · Cited by 250 · see citing works
Synaptic and plasticity-associated proteins in anterior frontal cortex in severe mental illness
Honer, W. G., Falkai, P., Chen, C., Arango, V., Mann, J. J., & Dwork, A. J. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00679-4 · Cited by 244 · see citing works
Review Article The family of sodium-dependent glutamate transporters: a focus on the GLT-1/EAAT2 subtype
Robinson, M. B. (1998) · Neurochemistry International · doi:10.1016/s0197-0186(98)00055-2 · Cited by 242 · see citing works
Lamina-Specific Reductions in Dendritic Spine Density in the Prefrontal Cortex of Subjects With Schizophrenia
Kolluri, N., Sun, Z., Sampson, A. R., & Lewis, D. A. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.6.1200 · Cited by 241 · see citing works
Negative schizophrenic symptomatology and the PCP (phencyclidine) model of schizophrenia.
Javitt, D. (1987) · PubMed · Cited by 240 · see citing works
Excitatory amino acid transporters: keeping up with glutamate
Amara, S., & Fontana, A. C. K. (2002) · Neurochemistry International · doi:10.1016/s0197-0186(02)00018-9 · Cited by 240 · see citing works
Decreased hippocampal expression of a glutamate receptor gene in schizophrenia
Harrison, P. J., McLaughlin, D. P., & Kerwin, R. W. (1991) · The Lancet · doi:10.1016/0140-6736(91)93392-m · Cited by 240 · see citing works
Molecular evidence of N-methyl-D-aspartate receptor hypofunction in schizophrenia
Weickert, C. S., Fung, S. J., Catts, V. S., Schofield, P. R., Allen, K. M., Moore, L., Newell, K. A., Pellen, D., Huang, X.-F., Catts, S. V., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.137 · Cited by 234 · see citing works
Ionotropic Glutamate Receptor Binding and Subunit mRNA Expression in Thalamic Nuclei in Schizophrenia
Ibrahim, H. M., Hogg, A. J., Healy, D. J., Haroutunian, V. H., Davis, K. L., & Meador‐Woodruff, J. H. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.11.1811 · Cited by 233 · see citing works
Astrocyte glutamine synthetase: pivotal in health and disease
Rose, C. F., Verkhratsky, A., & Parpura, V. (2013) · Biochemical Society Transactions · doi:10.1042/bst20130237 · Cited by 224 · see citing works
Evidence for a decrease in basilar dendrites of pyramidal cells in schizophrenic medial prefrontal cortex
Broadbelt, K. G. (2002) · Schizophrenia Research · doi:10.1016/s0920-9964(02)00201-3 · Cited by 224 · see citing works
Altered synaptophysin expression as a marker of synaptic pathology in schizophrenia
Eastwood, S. L., Burnet, P. W. J., & Harrison, P. J. (1995) · Neuroscience · doi:10.1016/0306-4522(94)00586-t · Cited by 223 · see citing works
Cofactors of serine racemase that physiologically stimulate the synthesis of the N -methyl- d -aspartate (NMDA) receptor coagonist d -serine
Miranda, J. D., Panizzutti, R., Foltyn, V. N., & Wolosker, H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222421299 · Cited by 221 · see citing works
Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia
Kristiansen, L. V., Beneyto, M., Haroutunian, V, & Meador-Woodruff, J. H. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001844 · Cited by 220 · see citing works
Detection of stimulus deviance within primate primary auditory cortex: intracortical mechanisms of mismatch negativity (MMN) generation
Javit, D. C., Steinschneider, M., Schroeder, C. E., Vaughan, H. G., & Arezzo, J. C. (1994) · Brain Research · doi:10.1016/0006-8993(94)91496-6 · Cited by 219 · see citing works
Multiple risk pathways for schizophrenia converge in serine racemase knockout mice, a mouse model of NMDA receptor hypofunction
Balu, D. T., Li, Y., Puhl, M. D., Benneyworth, M. A., Basu, A. C., Takagi, S., Bolshakov, V. Y., & Coyle, J. T. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1304308110 · Cited by 217 · see citing works
Alterations in synaptic proteins and their encoding mRNAs in prefrontal cortex in schizophrenia: a possible neurochemical basis for ‘hypofrontality’
Karson, C. N., Mrak, R. E., Schluterman, K. O., Sturner, W. Q., Sheng, J. G., & Griffin, W. S. T. (1999) · Molecular Psychiatry · doi:10.1038/sj.mp.4000459 · Cited by 211 · see citing works
Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia
Ohnuma, T., Augood, S. J., Arai, H., McKenna, P. J., & Emson, P. C. (1998) · Molecular Brain Research · doi:10.1016/s0169-328x(98)00063-1 · Cited by 210 · see citing works
Decreased expression of mRNAs encoding non-NMDA glutamate receptors GluRl and GluR2 in medial temporal lobe neurons in schizophrenia
Eastwood, S. L., McDonald, B., Burnet, P. W. J., Beckwith, J. P., Kerwin, R. W., & Harrison, P. J. (1995) · Molecular Brain Research · doi:10.1016/0169-328x(94)00247-c · Cited by 207 · see citing works
Defining cortical frequency tuning with recurrent excitatory circuitry
Liu, B.-H., Wu, G. K., Arbuckle, R., Tao, H. W., & Zhang, L. I. (2007) · Nature Neuroscience · doi:10.1038/nn2012 · Cited by 200 · see citing works
The Human Brain Revisited Opportunities and Challenges in Postmortem Studies of Psychiatric Disorders
Lewis, D. A. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00393-1 · Cited by 197 · see citing works
Decreased synaptophysin in the medial temporal lobe in schizophrenia demonstrated using immunoautoradiography
Eastwood, S. L., & Harrison, P. J. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00324-c · Cited by 193 · see citing works
Increased brain d-amino acid oxidase (DAAO) activity in schizophrenia
Madeira, C., Freitas, M. E., Vargas-Lopes, C., Wolosker, H., & Panizzutti, R. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.02.002 · Cited by 190 · see citing works
N-Methyl- d -Aspartic Acid Receptor Expression in the Dorsolateral Prefrontal Cortex of Elderly Patients With Schizophrenia
Dracheva, S. M., Marras, S. A. E., Elhakem, S. L., Kramer, F. R., Davis, K. L., & Haroutunian, V. H. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.9.1400 · Cited by 190 · see citing works
Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons
Eastwood, S. L., & Harrison, P. J. (2004) · Schizophrenia Research · doi:10.1016/j.schres.2004.05.010 · Cited by 187 · see citing works
Expression of NMDAR1, GluR1, GluR7, and KA1 Glutamate Receptor mRNAs Is Decreased in Frontal Cortex of “Neuroleptic‐Free” Schizophrenics: Evidence on Reversible Up‐Regulation by Typical Neuroleptics
Sokolov, B. P. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.71062454.x · Cited by 186 · see citing works
Abnormalities of the NMDA Receptor and Associated Intracellular Molecules in the Thalamus in Schizophrenia and Bipolar Disorder
Clinton, S. M., & Meador‐Woodruff, J. H. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300451 · Cited by 177 · see citing works
d ‐Amino acid oxidase and serine racemase in human brain: normal distribution and altered expression in schizophrenia
Louise, V., Walker, M. A., Rawlings, N. B., Benzel, I. M., Kew, J. N. C., Harrison, P. J., & Burnet, P. W. J. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05769.x · Cited by 176 · see citing works
Impaired precision, but normal retention, of auditory sensory ("echoic") memory information in schizophrenia.
Javitt, D. C., Strous, R. D., Grochowski, S., Ritter, W., & al, E. (1997) · Journal of Abnormal Psychology · doi:10.1037//0021-843x.106.2.315 · Cited by 168 · see citing works
Downregulated Kynurenine 3-Monooxygenase Gene Expression and Enzyme Activity in Schizophrenia and Genetic Association With Schizophrenia Endophenotypes
Wonodi, I., Stine, O. C., Sathyasaikumar, K. V., Roberts, R. C., Mitchell, B. D., Hong, L. E., Kajii, Y., Thaker, G. K., & Schwarcz, R. M. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.71 · Cited by 166 · see citing works
Levels of the growth-associated protein GAP-43 are selectively increased in association cortices in schizophrenia
Perrone-Bizzozero, N. I., Sower, A. C., Bird, E. D., Benowitz, L. I., Ivins, K. J., & Neve, R. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.14182 · Cited by 162 · see citing works
Glutamatergic abnormalities in schizophrenia: A review of proton MRS findings
Poels, E. M. P., Kegeles, L. S., Kantrowitz, J. T., Javitt, D. C., Lieberman, J. A., Abi‐Dargham, A., & Girgis, R. R. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2013.12.013 · Cited by 158 · see citing works
Distribution of kainate receptor subunit mRNAs in human hippocampus, neocortex and cerebellum, and bilateral reduction of hippocampal GluR6 and KA2 transcripts in schizophrenia
Porter, R. H. P., Eastwood, S. L., & Harrison, P. J. (1997) · Brain Research · doi:10.1016/s0006-8993(96)01404-7 · Cited by 158 · see citing works
The neuronal excitatory amino acid transporter EAAC1/EAAT3: does it represent a major actor at the brain excitatory synapse?
Nieoullon, A. L., Canolle, B., Masmejean, F., Guillet, B. A., Pisano, P. S., & Lortet, S. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03978.x · Cited by 155 · see citing works
Deviance-elicited Changes in Event-related Potentials are Attenuated by Ketamine in Mice
Ehrlichman, R. S., Maxwell, C. R., Majumdar, S., & Siegel, S. J. (2008) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.2008.20097 · Cited by 154 · see citing works
Distribution of Glutamate Transporter Subtypes During Human Brain Development
Bar-Peled, O., Ben‐Hur, H., Biegon, A. R., Groner, Y., Dewhurst, S., Furuta, A., & Rothstein, J. D. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69062571.x · Cited by 153 · see citing works
The dendritic architecture of prefrontal pyramidal neurons in schizophrenic patients
Kalus, P., Muller, T. J., Zuschratter, W., & Senitz, D. (2000) · NeuroReport · doi:10.1097/00001756-200011090-00044 · Cited by 146 · see citing works
Metabotropic glutamate receptor protein expression in the prefrontal cortex and striatum in schizophrenia
Gupta, D. S., McCullumsmith, R. E., Beneyto, M., Haroutunian, V., Davis, K. L., & Meador‐Woodruff, J. H. (2005) · Synapse · doi:10.1002/syn.20164 · Cited by 146 · see citing works
Cingulate cortex synaptic terminal proteins and neural cell adhesion molecule in schizophrenia
Honer, W. G., Falkai, P., Young, C., Wang, T., Xie, J., Bonner, J., Hu, L., Boulianne, G. L., Luo, Z., & Trimble, W. S. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00489-7 · Cited by 144 · see citing works
NR3A NMDA receptor subunit mRNA expression in schizophrenia, depression and bipolar disorder
Mueller, H. T., & Meador‐Woodruff, J. H. (2004) · Schizophrenia Research · doi:10.1016/j.schres.2004.02.016 · Cited by 139 · see citing works
Impaired precision, but normal retention, of auditory sensory ("echoic") memory information in schizophrenia.
Javitt, D. C., Strous, R. D., Grochowski, S., et al. (1997) · Journal of Abnormal Psychology · doi:10.1037/0021-843x.106.2.315 · Cited by 136 · see citing works
Glutamate receptor subtype expression in human postmortem brain tissue from schizophrenics and alcohol abusers
Breese, C. R., Freedman, R., & Leonard, S. S. (1995) · Brain Research · doi:10.1016/0006-8993(94)01384-t · Cited by 134 · see citing works
Increased concentrations of presynaptic proteins in the cingulate cortex of subjects with schizophrenia.
Gabriel, S., Haroutunian, V., Powchik, P., Honer, W. G., Davidson, M., Davies, P., & Davis, K. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830180077010 · Cited by 133 · see citing works
Cortical expression of glial fibrillary acidic protein and glutamine synthetase is decreased in schizophrenia
Steffek, A. E., McCullumsmith, R. E., Haroutunian, V. H., & Meador‐Woodruff, J. H. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.04.032 · Cited by 124 · see citing works
Presynaptic proteins in the prefrontal cortex of patients with schizophrenia and rats with abnormal prefrontal development
Halim, N. D., Weickert, C. S., McClintock, B. W., Hyde, T. M., Weinberger, D. R., Kleinman, J. E., & Lipska, B. K. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001319 · Cited by 124 · see citing works
Abnormal glycosylation of EAAT1 and EAAT2 in prefrontal cortex of elderly patients with schizophrenia
Bauer, D., Haroutunian, V. H., Meador‐Woodruff, J. H., & McCullumsmith, R. E. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.07.025 · Cited by 124 · see citing works
Auditory sensory ("echoic") memory dysfunction in schizophrenia
Strous, R. D., Cowan, N., Ritter, W., & Javitt, D. C. (1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.10.1517 · Cited by 122 · see citing works
Altered Transcript Expression of NMDA Receptor-Associated Postsynaptic Proteins in the Thalamus of Subjects With Schizophrenia
Clinton, S. M., Haroutunian, V. H., Davis, K. L., & Meador‐Woodruff, J. H. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.6.1100 · Cited by 119 · see citing works
Contributions of the d-serine pathway to schizophrenia
Labrie, V., Wong, A. H. C., & Roder, J. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.01.030 · Cited by 118 · see citing works
Spectral integration in primary auditory cortex: Laminar processing of afferent input, in vivo and in vitro
Kaur, S., Rose, H. J., Lazar, R., Liang, K., & Metherate, R. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.04.052 · Cited by 117 · see citing works
Serine racemase deletion disrupts memory for order and alters cortical dendritic morphology
DeVito, L. M., Balu, D. T., Kanter, B. R., Lykken, C., Basu, A. C., COYLE, J. T., & Eichenbaum, H. (2010) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2010.00656.x · Cited by 114 · see citing works
Lamina-specific abnormalities of AMPA receptor trafficking and signaling molecule transcripts in the prefrontal cortex in schizophrenia
Beneyto, M., & Meador‐Woodruff, J. H. (2006) · Synapse · doi:10.1002/syn.20329 · Cited by 113 · see citing works
Immunocytochemical localization of d-amino acid oxidase in rat brain
Moreno, S., Nardacci, R., Cimini, A., & Cer`, M. P. (1999) · Journal of Neurocytology · doi:10.1023/a:1007064504007 · Cited by 111 · see citing works
Alterations in Metabotropic Glutamate Receptor 1α and Regulator of G Protein Signaling 4 in the Prefrontal Cortex in Schizophrenia
Volk, D. W., Eggan, S. M., & Lewis, D. A. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.10030318 · Cited by 111 · see citing works
Abnormal expression of glutamate transporter and transporter interacting molecules in prefrontal cortex in elderly patients with schizophrenia
Bauer, D., Gupta, D. S., Harotunian, V., Meador‐Woodruff, J. H., & McCullumsmith, R. E. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.06.012 · Cited by 111 · see citing works
Reduced Pyramidal Cell Somal Volume in Auditory Association Cortex of Subjects with Schizophrenia
Sweet, R. A., Pierri, J. N., Auh, S., Sampson, A. R., & Lewis, D. A. (2002) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300120 · Cited by 108 · see citing works
Self-citation
Activity-Dependent Dendritic Spine Structural Plasticity Is Regulated by Small GTPase Rap1 and Its Target AF-6
Xie, Z., Huganir, R. L., & Penzes, P. (2005) · Neuron · doi:10.1016/j.neuron.2005.09.027 · Cited by 108 · see citing works
Vesicular glutamate transporter mRNA expression in the medial temporal lobe in major depressive disorder, bipolar disorder, and schizophrenia
Uezato, A., Meador‐Woodruff, J. H., & McCullumsmith, R. E. (2009) · Bipolar Disorders · doi:10.1111/j.1399-5618.2009.00752.x · Cited by 106 · see citing works
NMDA receptor mRNA correlation with antemortem cognitive impairment in schizophrenia
Humphries, C., Mortimer, A. M., Hirsch, S. R., & de Belleroche, J. (1996) · Neuroreport · doi:10.1097/00001756-199608120-00040 · Cited by 102 · see citing works
Pyramidal cell size reduction in schizophrenia: evidence for involvement of auditory feedforward circuits
Sweet, R. A., Bergen, S. E., Sun, Z., Sampson, A. R., Pierri, J. N., & Lewis, D. A. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.03.002 · Cited by 102 · see citing works
Self-citation
GluR2 glutamate receptor subunit flip and flop isoforms are decreased in the hippocampal formation in schizophrenia: a reverse transcriptase-polymerase chain reaction (RT–PCR) study
Eastwood, S. L., Burnet, P. W. J., & Harrison, P. J. (1997) · Molecular Brain Research · doi:10.1016/s0169-328x(96)00195-7 · Cited by 101 · see citing works
Synaptophysin gene expression in schizophrenia
Eastwood, S. L., Cairns, N. J., & Harrison, P. J. (2000) · The British Journal of Psychiatry · doi:10.1192/bjp.176.3.236 · Cited by 100 · see citing works
Immunoautoradiographic evidence for a loss of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate-preferring non-N-methyl-D-aspartate glutamate receptors within the medial temporal lobe in schizophrenia
Eastwood, S. L., Kerwin, R. W., & Harrison, P. J. (1997) · Biological Psychiatry · doi:10.1016/s0006-3223(96)00220-x · Cited by 100 · see citing works
The synaptic-vesicle-specific proteins rab3a and synaptophysin are reduced in thalamus and related cortical brain regions in schizophrenic brains
Davidsson, P., Gottfries, J., Bogdanović, N., Ekman, R., Karlsson, I., Gottfries, C., & Blennow, K. (1999) · Schizophrenia Research · doi:10.1016/s0920-9964(99)00037-7 · Cited by 100 · see citing works
The NMDA receptor co-agonists, d-serine and glycine, regulate neuronal dendritic architecture in the somatosensory cortex
Balu, D. T., Basu, A. C., Corradi, J., Cacace, A. M., & Coyle, J. T. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.10.006 · Cited by 99 · see citing works
Implications for Altered Glutamate and GABA Metabolism in the Dorsolateral Prefrontal Cortex of Aged Schizophrenic Patients
Gluck, M. R., Thomas, R. G., Davis, K. L., & Haroutunian, V. H. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.7.1165 · Cited by 98 · see citing works
Altered Vesicular Glutamate Transporter Expression in the Anterior Cingulate Cortex in Schizophrenia
Oni-Orisan, A., Kristiansen, L. V., Haroutunian, V. H., Meador‐Woodruff, J. H., & McCullumsmith, R. E. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.10.020 · Cited by 96 · see citing works
Astrocyte and Glutamate Markers in the Superficial, Deep, and White Matter Layers of the Anterior Cingulate Gyrus in Schizophrenia
Katsel, P., Byne, W. M., Roussos, P., Tan, W., Siever, L. J., & Haroutunian, V. H. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.252 · Cited by 96 · see citing works
Differential Expression of Metabotropic Glutamate Receptors 2 and 3 in Schizophrenia: A Mechanism for Antipsychotic Drug Action?
Ghose, S., Gleason, K., Potts, B. W., Lewis‐Amezcua, K., & Tamminga, C. A. (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.08091445 · Cited by 96 · see citing works
Glial fibrillary acidic protein and glutamine synthetase in subregions of prefrontal cortex in schizophrenia and mood disorder
Toro, C. T., Hallak, J. E. C., Dunham, J. S., & Deakin, J. F. W. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.05.067 · Cited by 95 · see citing works
Glutamine synthetase and glutamate dehydrogenase in the prefrontal cortex of patients with schizophrenia
Burbaeva, G. S., Бокша, И. С., Turishcheva, M. S., Vorobyeva, E. A., Savushkina, O. K., & Терешкина, Е. Б. (2003) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(03)00078-2 · Cited by 91 · see citing works
mRNA expression of AMPA receptors and AMPA receptor binding proteins in the cerebral cortex of elderly schizophrenics
Dracheva, S. M., McGurk, S. R., & Haroutunian, V. H. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20423 · Cited by 84 · see citing works
Glutamate Receptor Abnormalities in Schizophrenia: Implications for Innovative Treatments
Rubio, M. D., Drummond, J. B., & Meador‐Woodruff, J. H. (2012) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2012.20.1.001 · Cited by 83 · see citing works
Sex-specific proteome differences in the anterior cingulate cortex of schizophrenia
Martins‐de‐Souza, D., Schmitt, A., Röder, R., et al. (2010) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2010.03.003 · Cited by 82 · see citing works
Anatomical Evidence of Impaired Feedforward Auditory Processing in Schizophrenia
Sweet, R. A., Bergen, S. E., Sun, Z., Marcsisin, M. J., Sampson, A. R., & Lewis, D. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.07.033 · Cited by 81 · see citing works
Self-citation
Abnormal Kainate Receptor Expression in Prefrontal Cortex in Schizophrenia
Meador‐Woodruff, J. H. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00189-5 · Cited by 80 · see citing works
GluR<sub>5,6,7</sub> subunit immunoreactivity on apical pyramidal cell dendrites in hippocampus of schizophrenics and manic depressives
Benes, F. M., Todtenkopf, M. S., & Kostoulakos, P. (2001) · Hippocampus · doi:10.1002/hipo.1065 · Cited by 79 · see citing works
AMPA Receptor Binding and Subunit mRNA Expression in Prefrontal Cortex and Striatum of Elderly Schizophrenics
Healy, D. J., Haroutunian, V. H., Powchik, P., Davidson, M., Davis, K. L., Watson, S. J., & Meador‐Woodruff, J. H. (1998) · Neuropsychopharmacology · doi:10.1016/s0893-133x(98)00014-1 · Cited by 78 · see citing works
Altered levels of glutamatergic receptors and Na+/K+ ATPase-α1 in the prefrontal cortex of subjects with schizophrenia
Corti, C., Xuereb, J. H., Crepaldi, L., et al. (2011) · Schizophrenia Research · doi:10.1016/j.schres.2011.01.021 · Cited by 75 · see citing works
Metabotropic glutamate receptor mRNA expression in the schizophrenic thalamus
Richardson-Burns, S. M., Haroutunian, V. H., Davis, K. L., Watson, S. J., & Meador‐Woodruff, J. H. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00207-3 · Cited by 74 · see citing works
Preliminary evidence for a link between schizophrenia and NMDA–glycine site receptor ligand metabolic enzymes, d -amino acid oxidase (DAAO) and kynurenine aminotransferase-1 (KAT-1)
Kapoor, R., Lim, K. S., Cheng, A., Garrick, T. M., & Kapoor, V. (2006) · Brain Research · doi:10.1016/j.brainres.2006.05.082 · Cited by 73 · see citing works
Increased expression of glutaminase and glutamine synthetase mRNA in the thalamus in schizophrenia
Bruneau, E., McCullumsmith, R. E., Haroutunian, V. H., et al. (2005) · Schizophrenia Research · doi:10.1016/j.schres.2004.12.012 · Cited by 70 · see citing works
Abnormal expression of glutamate transporters in temporal lobe areas in elderly patients with schizophrenia
Shan, D., Lucas, E. K., Drummond, J. B., Haroutunian, V. H., Meador‐Woodruff, J. H., & McCullumsmith, R. E. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2012.12.019 · Cited by 69 · see citing works
Cortical Glutamatergic Markers in Schizophrenia
Scarr, E., Beneyto, M., Meador‐Woodruff, J. H., & Dean, B. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300758 · Cited by 67 · see citing works
AMPA Receptor Binding and Subunit mRNA Expression in Prefrontal Cortex and Striatum of Elderly Schizophrenics
Healy, D. J., Haroutunian, V. H., Powchik, P., et al. (1998) · Neuropsychopharmacology · doi:10.1038/sj.npp.1395198 · Cited by 67 · see citing works
Somal size of prefrontal cortical pyramidal neurons in schizophrenia
Pierri, J. N., Volk, C. L. E., Auh, S., Sampson, A. R., & Lewis, D. A. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00294-4 · Cited by 64 · see citing works
Differential spine loss and regrowth of striatal neurons following multiple forms of deafferentation: a Golgi study
Cheng, H.-W., Rafols, J. A., Goshgarian, H. G., Anavi, Y., Tong, J., & McNeill, T. H. (1997) · Experimental Neurology · doi:10.1006/exnr.1997.6618 · Cited by 64 · see citing works
Altered Glutamate Protein Co-Expression Network Topology Linked to Spine Loss in the Auditory Cortex of Schizophrenia
MacDonald, M. L., Ding, Y., Newman, J. T., Hemby, S. E., Penzes, P., Lewis, D. A., Yates, N. A., & Sweet, R. A. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.09.006 · Cited by 64 · see citing works
Self-citation
The first decade and beyond of transcriptional profiling in schizophrenia
Sequeira, A., Martin, M. V., & Vawter, M. P. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.03.001 · Cited by 64 · see citing works
Up‐regulation of NMDA receptor subunit and post‐synaptic density protein expression in the thalamus of elderly patients with schizophrenia
Clinton, S. M., Haroutunian, V. H., & Meador‐Woodruff, J. H. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03954.x · Cited by 64 · see citing works
Comparative analysis of group II metabotropic glutamate receptor immunoreactivity in Brodmann's area 46 of the dorsolateral prefrontal cortex from patients with schizophrenia and normal subjects
Crook, J. M., Akil, M., Law, B., Hyde, T. M., & Kleinman, J. E. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4000966 · Cited by 60 · see citing works
Localization of D-amino acid oxidase in Bergmann glial cells and astrocytes of rat cerebellum
Horiike, K., Tojo, H., Arai, R., et al. (1987) · Brain Research Bulletin · doi:10.1016/0361-9230(87)90076-1 · Cited by 59 · see citing works
Increased levels of expression of an NMDAR1 splice variant in the superior temporal gyrus in schizophrenia
Corre, S. L., Harper, C. G., López-García, P., Ward, P. B., & Catts, S. V. (2000) · Neuroreport · doi:10.1097/00001756-200004070-00017 · Cited by 55 · see citing works
Lack of Change in Markers of Presynaptic Terminal Abundance Alongside Subtle Reductions in Markers of Presynaptic Terminal Plasticity in Prefrontal Cortex of Schizophrenia Patients
Fung, S. J., Sivagnanasundaram, S., & Weickert, C. S. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.09.036 · Cited by 54 · see citing works
Potential pathophysiological role of d-amino acid oxidase in schizophrenia: immunohistochemical and in situ hybridization study of the expression in human and rat brain
Ono, K., Shishido, Y., Park, H. K., Kawazoe, T., Iwana, S., Chung, S. P., El-Magd, R. M. A., Yorita, K., Okano, M., Watanabe, T., et al. (2009) · Journal of Neural Transmission · doi:10.1007/s00702-009-0289-7 · Cited by 53 · see citing works
Reduced neuron density, enlarged minicolumn spacing and altered ageing effects in fusiform cortex in schizophrenia
Rosa, E. D., Crow, T. J., Walker, M. A., Black, G. B., & Chance, S. A. (2009) · Psychiatry Research · doi:10.1016/j.psychres.2008.04.007 · Cited by 53 · see citing works
High‐affinity Na+/K+‐dependent glutamate transporter EAAT4 is expressed throughout the rat fore‐ and midbrain
Massie, A., Cnops, L., Smolders, I. J., McCullumsmith, R. E., Kooijman, R., Kwak, S., Arckens, L., & Michotte, Y. M. (2008) · The Journal of Comparative Neurology · doi:10.1002/cne.21823 · Cited by 53 · see citing works
Elevated GRIA1 mRNA expression in Layer II/III and V pyramidal cells of the DLPFC in schizophrenia
O’Connor, J. A., & Hemby, S. E. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2007.09.022 · Cited by 53 · see citing works
Glutamatergic Gene Expression Is Specifically Reduced in Thalamocortical Projecting Relay Neurons in Schizophrenia
Sodhi, M., Simmons, M. S., McCullumsmith, R. E., Haroutunian, V. H., & Meador‐Woodruff, J. H. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.02.022 · Cited by 52 · see citing works
Expression of the Hippocampal NMDA Receptor GluN1 Subunit and Its Splicing Isoforms in Schizophrenia: Postmortem Study
Vrajová, M., Šťastný, F., Horáček, J., Lochman, J., Šerý, O., Peková, Š., Klaschka, J., & Höschl, C. (2010) · Neurochemical Research · doi:10.1007/s11064-010-0145-z · Cited by 52 · see citing works
Evidence for reduced neuronal somal size within the insular cortex in schizophrenia, but not in affective disorders
Pennington, K., Dicker, P., Hudson, L., & Cotter, D. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.08.022 · Cited by 51 · see citing works
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“Moreover, non-Bayesian alternatives—such as models based on disordered neuromodulation (Hu et al. 2015), disrupted synaptic pruning (Sekar et al. 2016), or abnormal cortical dynamics (Uhlhaas et al. 2009)—can also account for similar symptom profiles without invoking probabilistic inference.”

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Authors: Hu, W., MacDonald, M. L., Elswick, D. E., & Sweet, R. A.
Affiliations: West Virginia University (US)
University of Pittsburgh (US)
Corresponding author: Sweet, Robert A.
ORCID: Hu, Wei
MacDonald, Matthew L.
Elswick, Daniel E.
Sweet, Robert A.
Venue: Annals of the New York Academy of Sciences
Publisher: Wiley
Published: 2014-10-14
Volume: 1338
Issue: 1
Pages: 38-57
ISSN: 0077-8923 (ISSN-L)
1749-6632
DOI: 10.1111/nyas.12547
PMC: PMC4363164
OpenAlex: W1924382915
Cited by: 286
References: 184
Citations by year: 2026: 18 · 2025: 22 · 2024: 42 · 2023: 21 · 2022: 31 · 2021: 23 · 2020: 24 · 2019: 21 · 2018: 19 · 2017: 33 · 2016: 16 · 2015: 15 · 2012: 1
FWCI: 2.94
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Annals of the New York Academy of Sciences (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (MH071533, MH103204, MH16804)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords: NMDA receptor antagonists, glutamatergic neurons, dendritic morphology, synaptophysin, glutamate receptors, GLT-1, glutamine synthetase, glutaminase, glutamate metabolism, cerebral cortex, postmortem brain, synaptic dysfunction
MeSH terms: Brain, Female, Humans, Male, RNA, Messenger, Schizophrenia, Receptors, Glutamate, Glutamic Acid

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The glutamate hypothesis of schizophrenia: evidence from human brain tissue studies

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