Glutamate receptor dysfunction and schizophrenia

Olney, John W.

doi:10.1001/archpsyc.1995.03950240016004

Cited by 1,685Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

Glutamate receptor dysfunction and schizophrenia

Olney, John W.·1995·Archives of General Psychiatry

DOI 10.1001/archpsyc.1995.03950240016004

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Abstract

In this article, we advance a unified hypothesis pertaining to combined dysfunction of dopamine and N-methyl-D-aspartate glutamate receptors that highlights N-methyl-D-aspartate receptor hypofunction as a key mechanism that can help explain major clinical and pathophysiological aspects of schizophrenia. The following fundamental features of schizophrenia are accommodated by this hypothesis: (1) the occurrence of structural brain changes during early development that have the potential for producing subsequent clinical manifestations of schizophrenia, (2) a quiescent period in infancy and adolescence before clinical manifestations are expressed, (3) onset in early adulthood of psychotic symptoms, (4) involvement of dopamine (D2) receptors in some cases but not others that would explain why some but not all patients are responsive to typical neuroleptic therapy, and (5) ongoing neurodegenerative changes and cognitive deterioration in some patients. We propose that since N-methyl-D-aspartate receptor hypofunction can cause psychosis in humans and corticolimbic neurodegenerative changes in the rat brain, and since these changes are prevented by certain antipsychotic drugs, including atypical neuroleptic agents (clozapine, olanzapine, fluperlapine), a better understanding of the N-methyl-D-aspartate receptor hypofunction mechanism and ways of preventing its neurodegenerative consequences in the rat brain may lead to improved pharmacotherapy in schizophrenia.

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Increasing evidence supports dysfunction of the glutaminergic system as the primary pathophysiological change seen in schizophrenia.
“In recent years, however, increasing evidence supports dysfunction of the glutaminergic system as being the primary pathophysiological changes seen in schizophrenia [105].”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [105]
The resemblance between patient contrast response curves and NMDA antagonist effects is consistent with glutamatergic theories of schizophrenia.
“The decreased slope at low contrast and decreased plateau in patients closely resembles results seen after microinfusion of an NDMA antagonist into cat LGN and visual cortex (16,17) (Figure 3A and 3B), consistent with glutamatergic theories of schizophrenia (23–25).”
From Visual perception and its impairment in schizophrenia (2008) · cites this paper as [24]
The decreased slope at low contrast and decreased plateau in patients closely resembles results seen after microinfusion of an NMDA antagonist into cat LGN and visual cortex.
“The decreased slope at low contrast and decreased plateau in patients closely resembles results seen after microinfusion of an NDMA antagonist into cat LGN and visual cortex (16,17) (Figure 3A and 3B), consistent with glutamatergic theories of schizophrenia (23–25).”
From Visual perception and its impairment in schizophrenia (2008) · cites this paper as [24]

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A review of MRI findings in schizophrenia
Shenton, M. E., Dickey, C. C., Frumin, M., & McCarley, R. W. (2001) · Schizophrenia Research · doi:10.1016/s0920-9964(01)00163-3 · Cited by 2,346 · see citing works
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NMDA Receptor Hypofunction Produces Opposite Effects on Prefrontal Cortex Interneurons and Pyramidal Neurons
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Increased baseline occupancy of D 2 receptors by dopamine in schizophrenia
Abi-Dargham, A., Rodenhiser, J., Printz, D., Zea-Ponce, Y., Gil, R., Kegeles, L. S., Weiss, R., Cooper, T. B., Mann, J. J., Van Heertum, R. L., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.14.8104 · Cited by 1,020 · see citing works
NMDA receptor hypofunction model of schizophrenia
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Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs
Miyamoto, S., Duncan, G. E., Marx, C. E., & Lieberman, J. A. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001556 · Cited by 988 · see citing works
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The Computational Anatomy of Psychosis
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“NMDA-Rs play a central role in theories of schizophrenia (Olney and Farber, 1995; Abi-Saab et al., 1998; Goff and Coyle, 2001; Stephan et al., 2006; Corlett et al., 2011).”
BackgroundMethod
White Matter Changes in Schizophrenia: Evidence for Myelin-Related Dysfunction
Davis, K. L., Stewart, D. G., Friedman, J. I., Buchsbaum, M., Harvey, P. D., Hof, P. R., Buxbaum, J., & Haroutunian, V. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.5.443 · Cited by 793 · see citing works
Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes
Belforte, J. E., Zsiros, V., Sklar, E. R., Jiang, Z., Yu, G., Li, Y., Quinlan, E. M., & Nakazawa, K. (2010) · Nature Neuroscience · doi:10.1038/nn.2447 · Cited by 752 · see citing works
Glutamate and dopamine in schizophrenia: An update for the 21 st century
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Functional and Anatomical Aspects of Prefrontal Pathology in Schizophrenia
Goldman-Rakic, P. S., & Selemon, L. D. (1997) · Schizophrenia Bulletin · doi:10.1093/schbul/23.3.437 · Cited by 668 · see citing works
Half a century of antipsychotics and still a central role for dopamine D2 receptors
Kapur, S., & Mamo, D. (2003) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2003.09.004 · Cited by 638 · 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
Glutamatergic mechanisms in schizophrenia
Tsai, G., & Coyle, J. T. (2002) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.42.082701.160735 · Cited by 577 · see citing works
N-Acetyl Cysteine as a Glutathione Precursor for Schizophrenia—A Double-Blind, Randomized, Placebo-Controlled Trial
Berk, M., Copolov, D., Dean, O., Lu, K., Jeavons, S., Schapkaitz, I., Anderson-Hunt, M., Judd, F., Katz, F., Katz, P., et al. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.03.004 · Cited by 552 · see citing works
Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo
Do, K. Q., Trabesinger, A. H., Kirsten‐Krüger, M., Lauer, C. J., Dydak, U., Hell, D., Holsboer, F., Boesiger, P., & Cuénod, M. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00229.x · Cited by 540 · see citing works
A Follow-up Magnetic Resonance Imaging Study of Schizophrenia: Relationship of Neuroanatomical Changes to Clinical and Neurobehavioral Measures
Gur, R. E., Cowell, P., Turetsky, B. I., Gallacher, F., Cannon, T., Bilker, W., & Gur, R. C. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.2.145 · Cited by 540 · see citing works
NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development
Krystal, J. H., D'Souza, D. C., Mathalon, D., Perry, E., Belger, A., & Hoffman, R. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1582-z · Cited by 530 · see citing works
Serotonin model of schizophrenia: emerging role of glutamate mechanisms
Aghajanian, G. (2000) · Brain Research Reviews · doi:10.1016/s0165-0173(99)00046-6 · Cited by 529 · see citing works
GABAergic interneuron origin of schizophrenia pathophysiology
Nakazawa, K., Zsiros, V., Jiang, Z., Nakao, K., Kolata, S., Zhang, S., & Belforte, J. E. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.01.022 · Cited by 498 · see citing works
Pharmacology and behavioral pharmacology of the mesocortical dopamine system
Tzschentke, T. M. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00033-2 · Cited by 481 · see citing works
Disrupted prediction-error signal in psychosis: Evidence for an associative account of delusions
Corlett, P. R., Murray, G. K., Honey, G. D., Aitken, M. R. F., Shanks, D. R., Robbins, T. W., Bullmore, E. T., Dickinson, A., & Fletcher, P. C. (2007) · Brain · doi:10.1093/brain/awm173 · Cited by 460 · see citing works
Visual perception and its impairment in schizophrenia
Butler, P. D., Silverstein, S. M., & Dakin, S. C. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.03.023 · Cited by 472 · see citing works
Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies
Marsman, A., van den Heuvel, M. P., Klomp, D. W. J., Kahn, R. S., Luijten, P. R., & Hulshoff Pol, H. E. (2013) · Schizophrenia Bulletin · doi:10.1093/schbul/sbr069 · Cited by 457 · see citing works
Convergence of biological and psychological perspectives on cognitive coordination in schizophrenia
Phillips, W. A., & Silverstein, S. M. (2003) · Behavioral and Brain Sciences · doi:10.1017/s0140525x03000025 · Cited by 445 · see citing works
NMDA receptor hypofunction produces concomitant firing rate potentiation and burst activity reduction in the prefrontal cortex
Jackson, M. E., Homayoun, H., & Moghaddam, B. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308455101 · Cited by 430 · see citing works
Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia
Hof, P. R., Haroutunian, V., Friedrich, V. L., Byne, W., Buitron, C., Perl, D. P., & Davis, K. L. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00237-3 · Cited by 433 · see citing works
Glutamate, Dopamine, and Schizophrenia: From Pathophysiology to Treatment
LARUELLE, M., KEGELES, L. S., & ABI‐DARGHAM, A. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1300.063 · Cited by 437 · see citing works
Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains
Torrey, E. F., Barci, B. M., Webster, M. J., Bartko, J. J., Meador-Woodruff, J. H., & Knable, M. B. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.10.019 · Cited by 426 · see citing works
Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine: Support for Hyperglutamatergic Effects ofN-methyl-D-aspartate Receptor Antagonists
Anand, A., Charney, D. S., Oren, D. A., Berman, R. M., Hu, X. S., Cappiello, A., & Krystal, J. H. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.3.270 · Cited by 426 · see citing works
The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments
Buchanan, R. W., Javitt, D. C., Marder, S. R., Schooler, N. R., Gold, J. M., McMahon, R. P., Heresco-Levy, U., & Carpenter, W. T. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.06081358 · Cited by 419 · see citing works
Adenosine receptors and brain diseases: neuroprotection and neurodegeneration
Gomes, C. V., Kaster, M. P., Tomé, A. R., Agostinho, P. M., & Cunha, R. A. (2011) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2010.12.001 · Cited by 419 · see citing works
Density of Glutamic Acid Decarboxylase 67 Messenger RNA–ContainingNeurons That Express the N-Methyl-D-AspartateReceptor Subunit NR2A in the Anterior Cingulate Cortex in Schizophreniaand Bipolar Disorder
Woo, T.-U. W., Walsh, J. P., & Benes, F. M. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.7.649 · Cited by 411 · see citing works
Neural development, cell-cell signaling, and the “two-hit” hypothesis of schizophrenia
Maynard, T. M., Sikich, L., Lieberman, J. A., & LaMantia, A.-S. (2001) · Schizophrenia Bulletin · doi:10.1093/oxfordjournals.schbul.a006887 · Cited by 383 · see citing works
Nature of Glutamate Alterations in Schizophrenia: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies
Merritt, K., Egerton, A., Kempton, M. J., Taylor, M. J., & McGuire, P. K. (2016) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.0442 · Cited by 367 · see citing works
Early-stage visual processing and cortical amplification deficits in schizophrenia
Butler, P. D., Zemon, V., Schechter, I., Saperstein, A. M., Hoptman, M. J., Lim, K. O., Revheim, N., Silipo, G., & Javitt, D. C. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.5.495 · Cited by 362 · see citing works
Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment
Konradi, C., & Heckers, S. (2003) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(02)00328-5 · Cited by 336 · see citing works
A Specific Role for NR2A-Containing NMDA Receptors in the Maintenance of Parvalbumin and GAD67 Immunoreactivity in Cultured Interneurons
Kinney, J. W., Davis, C. N., Tabarean, I., Conti, B., Bartfai, T., & Behrens, M. M. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4722-05.2006 · Cited by 329 · see citing works
N-Methyl d-Aspartate Receptor Antagonists Ketamine and MK-801 Induce Wake-Related Aberrant γ Oscillations in the Rat Neocortex
Pinault, D. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.10.006 · Cited by 315 · 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
Glutamate and the Neural Basis of the Subjective Effects of Ketamine: A Pharmaco–Magnetic Resonance Imaging Study
Deakin, J. F. W., Lees, J., McKie, S., Hallak, J. E. C., Williams, S. R., & Dursun, S. M. (2008) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2007.37 · Cited by 311 · see citing works
Effects of Ketamine on Anterior Cingulate Glutamate Metabolism in Healthy Humans: A 4-T Proton MRS Study
Rowland, L. M., Bustillo, J. R., Mullins, P. G., Jung, R. E., Lenroot, R., Landgraf, E., Barrow, R., Yeo, R., Lauriello, J., & Brooks, W. M. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.2.394 · Cited by 304 · see citing works
Altered excitatory-inhibitory balance in the NMDA-hypofunction model of schizophrenia
Kehrer, C. (2008) · Frontiers in Molecular Neuroscience · doi:10.3389/neuro.02.006.2008 · Cited by 287 · see citing works
The glutamate hypothesis of schizophrenia: evidence from human brain tissue studies
Hu, W., MacDonald, M. L., Elswick, D. E., & Sweet, R. A. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12547 · Cited by 286 · see citing works
Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy
Mao, X. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.1519 · Cited by 296 · see citing works
Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments
Butler, P. D., Martinez, A., Foxe, J. J., Kim, D., Zemon, V., Silipo, G., Mahoney, J., Shpaner, M., Jalbrzikowski, M., & Javitt, D. C. (2007) · Brain · doi:10.1093/brain/awl233 · Cited by 292 · see citing works
Antioxidants, Redox Signaling, and Pathophysiology in Schizophrenia: An Integrative View
Yao, J. K., & Keshavan, M. S. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3603 · Cited by 285 · see citing works
Reduced d-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients
Hashimoto, K., Engberg, G., Shimizu, E., Nordin, C., Lindström, L. H., & Iyo, M. (2005) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2005.04.023 · Cited by 267 · see citing works
Anatomical Abnormalities of the Anterior Cingulate Cortex in Schizophrenia: Bridging the Gap Between Neuroimaging and Neuropathology
Fornito, A., Yucel, M., Dean, B., Wood, S. J., & Pantelis, C. (2009) · Schizophrenia Bulletin · doi:10.1093/schbul/sbn025 · Cited by 259 · see citing works
Ketamine: NMDA Receptors and Beyond
Zorumski, C. F., Izumi, Y., & Mennerick, S. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.1547-16.2016 · Cited by 254 · see citing works
How can drug discovery for psychiatric disorders be improved?
Agid, Y., Buzsáki, G., Diamond, D. M., Frackowiak, R., Giedd, J., Girault, J.-A., Grace, A., Lambert, J. J., Manji, H., Mayberg, H., et al. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2217 · Cited by 240 · see citing works
Perceptual organization, the disorganization syndrome, and context processing in chronic schizophrenia
Silverstein, S. M., Kovács, I., Corry, R., & Valone, C. (2000) · Schizophrenia Research · doi:10.1016/s0920-9964(99)00180-2 · Cited by 240 · see citing works
Glutamate dysfunction in people with prodromal symptoms of psychosis: relationship to gray matter volume
Stone, J. M., Day, F., Tsagaraki, H., Valli, I., McLean, M. A., Lythgoe, D. J., O'Gorman, R. L., Barker, G. J., & McGuire, P. K. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.05.006 · Cited by 231 · see citing works
Glutamatergic model psychoses: prediction error, learning, and inference
Corlett, P. R., Honey, G. D., Krystal, J. H., & Fletcher, P. C. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.163 · Cited by 229 · see citing works
Novel Findings from CNVs Implicate Inhibitory and Excitatory Signaling Complexes in Schizophrenia
Pocklington, A. J., Rees, E., Walters, J. T. R., Han, J., Kavanagh, D. H., Chambert, K. D., Holmans, P., Moran, J. L., McCarroll, S. A., Kirov, G., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.04.022 · Cited by 193 · see citing works
Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat
López-Gil, X., Babot, Z., Amargós-Bosch, M., Suñol, C., Artigas, F., & Adell, A. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301356 · Cited by 183 · see citing works
Longitudinal grey-matter and glutamatergic losses in first-episode schizophrenia
Théberge, J., Williamson, K. E., Aoyama, N., Drost, D. J., Manchanda, R., Malla, A. K., Northcott, S., Menon, R. S., Neufeld, R. W. J., Rajakumar, N., et al. (2007) · British Journal of Psychiatry · doi:10.1192/bjp.bp.106.033670 · Cited by 185 · see citing works
Reduced size and abnormal asymmetry of parietal cortex in women with borderline personality disorder
Irle, E., Lange, C., & Sachsse, U. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.10.004 · Cited by 182 · see citing works
Mechanisms of action of second generation antipsychotic drugs in schizophrenia: insights from brain imaging studies
Abi-Dargham, A., & Laruelle, M. (2005) · European Psychiatry · doi:10.1016/j.eurpsy.2004.11.003 · Cited by 179 · see citing works
Potential Psychiatric Applications of Metabotropic Glutamate Receptor Agonists and Antagonists
Krystal, J. H., Mathew, S. J., DʼSouza, D. C., Garakani, A., Gunduz-Bruce, H., & Charney, D. S. (2010) · CNS Drugs · doi:10.2165/11533230-000000000-00000 · Cited by 180 · see citing works
Glutamate receptors in the rat medial prefrontal cortex regulate set-shifting ability
Stefani, M. R., Groth, K., & Moghaddam, B. (2003) · Behavioral Neuroscience · doi:10.1037/0735-7044.117.4.728 · Cited by 164 · see citing works
Assessment of Glutamate Transporter GLAST (EAAT1)-Deficient Mice for Phenotypes Relevant to the Negative and Executive/Cognitive Symptoms of Schizophrenia
Karlsson, R.-M., Tanaka, K., Saksida, L. M., Bussey, T. J., Heilig, M., & Holmes, A. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2008.215 · Cited by 165 · see citing works
Differential role of NR2A and NR2B subunits in N-Methyl-D-Aspartate receptor antagonist-induced aberrant cortical gamma oscillations
Kocsis, B. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.10.002 · Cited by 159 · see citing works
Dysfunctional long-term potentiation-like plasticity in schizophrenia revealed by transcranial direct current stimulation
Hasan, A., Nitsche, M. A., Rein, B., Schneider-Axmann, T., Guse, B., Gruber, O., Falkai, P., & Wobrock, T. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.05.017 · Cited by 156 · see citing works
1H-MRS at 4 Tesla in minimally treated early schizophrenia
Bustillo, J. R., Rowland, L. M., Mullins, P., Jung, R., Chen, H., Qualls, C., Hammond, R., Brooks, W. M., & Lauriello, J. (2010) · Molecular Psychiatry · doi:10.1038/mp.2009.121 · Cited by 153 · see citing works
A single application of MK801 causes symptoms of acute psychosis, deficits in spatial memory, and impairment of synaptic plasticity in rats
Manahan‐Vaughan, D., von Haebler, D., Winter, C., Juckel, G., & Heinemann, U. (2008) · Hippocampus · doi:10.1002/hipo.20367 · Cited by 149 · see citing works
Perceptual grouping in disorganized schizophrenia
Uhlhaas, P. J., Phillips, W. A., Mitchell, G., & Silverstein, S. M. (2006) · Psychiatry Research · doi:10.1016/j.psychres.2005.10.016 · Cited by 149 · see citing works
Glutamatergic deficits and parvalbumin-containing inhibitory neurons in the prefrontal cortex in schizophrenia
Bitanihirwe, B., Lim, M., Kelley, J., Kaneko, T., & Woo, T. (2009) · BMC Psychiatry · doi:10.1186/1471-244x-9-71 · Cited by 137 · see citing works
Dysfunctional neural plasticity in patients with schizophrenia
Daskalakis, Z. J., Christensen, B. K., Fitzgerald, P. B., & Chen, R. (2008) · Archives of General Psychiatry · doi:10.1001/archpsyc.65.4.378 · Cited by 130 · see citing works
At Issue: Schizophrenia and Rheumatoid Arthritis: The Negative Association Revisited
Oken, R. J., & Schulzer, M. (1999) · Schizophrenia Bulletin · doi:10.1093/oxfordjournals.schbul.a033407 · Cited by 129 · see citing works
Can Long-Term Outcomes Be Improved by Shortening the Duration of Untreated Illness in Psychiatric Disorders? A Conceptual Framework
Dell’Osso, B., Glick, I. D., Baldwin, D. S., & Altamura, A. C. (2013) · Psychopathology · doi:10.1159/000338608 · Cited by 118 · see citing works
Prenatal exposure to an NMDA receptor antagonist, MK-801 reduces density of parvalbumin-immunoreactive GABAergic neurons in the medial prefrontal cortex and enhances phencyclidine-induced hyperlocomotion but not behavioral sensitization to methamphetamine in postpubertal rats
Abekawa, T., Ito, K., Nakagawa, S., & Koyama, T. (2007) · Psychopharmacology · doi:10.1007/s00213-007-0729-8 · Cited by 118 · see citing works
Comparing the actions of lanicemine and ketamine in depression: key role of the anterior cingulate
Downey, D., Dutta, A., McKie, S., Dawson, G. R., Dourish, C. T., Craig, K., Smith, M. A., McCarthy, D. J., Harmer, C. J., Goodwin, G. M., et al. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2016.03.006 · Cited by 116 · see citing works
The relationship between cortical glutamate and striatal dopamine in first-episode psychosis: a cross-sectional multimodal PET and magnetic resonance spectroscopy imaging study
Jauhar, S., McCutcheon, R., Borgan, F., Veronese, M., Nour, M., Pepper, F., Rogdaki, M., Stone, J., Egerton, A., Turkheimer, F., et al. (2018) · The Lancet Psychiatry · doi:10.1016/s2215-0366(18)30268-2 · Cited by 114 · see citing works
The role of cortical inhibition in the pathophysiology and treatment of schizophrenia
Daskalakis, Z. J., Fitzgerald, P. B., & Christensen, B. K. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.09.006 · Cited by 111 · see citing works
Left temporal lobe structural and functional abnormality underlying auditory hallucinations
Hugdahl, K. (2009) · Frontiers in Neuroscience · doi:10.3389/neuro.01.001.2009 · Cited by 112 · see citing works
“A glutamate hypothesis has been proposed for schizophrenia (see Carlsson et al., 1999; Kehrer et al., 2008; Olney and Farber, 1995), suggesting that glutamate function in addition to dopamine function may be altered in patients with schizophrenia.”
Background
A transcranial magnetic stimulation study of inhibitory deficits in the motor cortex in patients with schizophrenia
Fitzgerald, P. B., Brown, T. L., Daskalakis, Z. J., & Kulkarni, J. (2002) · Psychiatry Research: Neuroimaging · doi:10.1016/s0925-4927(02)00002-1 · Cited by 110 · see citing works
Gamma oscillation deficits and the onset and early progression of schizophrenia
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Authors: Olney, J. W.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Olney, John W.
Venue: Archives of General Psychiatry
Publisher: American Medical Association (AMA)
Published: 1995-12-01
Volume: 52
Issue: 12
Pages: 998
ISSN: 0003-990X (ISSN-L)
DOI: 10.1001/archpsyc.1995.03950240016004
OpenAlex: W2093248761
Cited by: 1,685
References: 99
Citations by year: 2026: 20 · 2025: 13 · 2024: 17 · 2023: 23 · 2022: 35 · 2021: 37 · 2020: 44 · 2019: 49 · 2018: 37 · 2017: 49 · 2016: 51 · 2015: 52 · 2014: 53 · 2013: 54 · 2012: 62
FWCI: 45.32
Type: journal article
Language: en
Open access: closed
Locations: Archives of General Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1r01da006454-01)
National Institute on Drug Abuse (R01DA005072, DA07261, DA05072, T32DA007261, DA 06454)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: schizophrenia, NMDA receptor hypofunction, dopamine D2 receptor, psychosis, atypical antipsychotics, clozapine, olanzapine, neurodegeneration, brain development, cognitive decline
MeSH terms: Animals, Brain, Gyrus Cinguli, Microscopy, Electron, Models, Neurological, Schizophrenia, Receptors, N-Methyl-D-Aspartate, Receptors, Glutamate, Pyramidal Cells, Rats

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Glutamate receptor dysfunction and schizophrenia

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