NMDA receptor hypofunction model of schizophrenia
Abstract
Several decades of research attempting to explain schizophrenia in terms of the dopamine hyperactivity hypothesis have produced disappointing results. A new hypothesis focusing on hypofunction of the NMDA glutamate transmitter system is emerging as a potentially more promising concept. In this article, we present a version of the NMDA receptor hypofunction hypothesis that has evolved from our recent studies pertaining to the neurotoxic and psychotomimetic effects of PCP and related NMDA antagonist drugs. In this article, we examine this hypothesis in terms of its strengths and weaknesses, its therapeutic implications and ways in which it can be further tested.
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This results in disinhibition and hyperactivity of excitatory pathways, which will eventually cause neuronal damage.
“This results in disinhibition and hyperactivity of excitatory pathways, which will eventually cause neuronal damage.17”
From Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies (2013) · cites this paper as [17]
The NMDA-receptor hypofunction hypothesis was evolved from studies with NMDA-receptor antagonists, such as PCP and ketamine.
“The NMDA-receptor hypofunction hypothesis was evolved from studies with NMDA-receptor antagonists, such as PCP and ketamine.17”
From Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies (2013) · cites this paper as [17]
Diminished glutamate receptor activation, in particular of the NMDA-type, may be a possible underlying mechanism of reduced synaptic activity because NMDA-receptor antagonists produce the same symptoms as those seen in schizophrenia.
“In fact, diminished glutamate receptor activation, in particular of the NMDA-type of glutamate receptor, may be a possible underlying mechanism of reduced synaptic activity because NMDA-receptor antagonists produce the same symptoms as those seen in schizophrenia.17,18,25”
From Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies (2013) · cites this paper as [17]
The hypothesis that the exceptionally high metabolic rate of the posterior cingulate and precuneus adds to their vulnerability receives some support from animal models of schizophrenia based on pharmacologically induced excitatory amino acid toxicity that preferentially targets this area.
“This hypothesis receives some support from animal models of schizophrenia (36), based on pharmacologically induced, excitatory amino acid toxicity that preferentially (but without explanation to date) targets this area.”
From A default mode of brain function (2001) · cites this paper as [36]
Cites
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
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
Excitatory Amino Acid Transmitters
Watkins, J. C., & Evans, R. H. (1981) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.21.040181.001121 · Cited by 2,497 · see citing works
Blockade of NMDA Receptors and Apoptotic Neurodegeneration in the Developing Brain
Ikonomidou, C., Bosch, F., Miksa, M., Bittigau, P., Vöckler, J., Dikranian, K., Tenkova, T. I., Stefovska, V., Turski, L., & Olney, J. W. (1999) · Science · doi:10.1126/science.283.5398.70 · Cited by 2,055 · see citing works
Self-citationMoghaddam, B., Adams, B., Verma, A., & Daly, D. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-08-02921.1997 · Cited by 1,793 · 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
Self-citationKetamine—its pharmacology and therapeutic uses
white, P. F., Way, W. L., & Trevor, A. J. (1982) · Anesthesiology · doi:10.1097/00000542-198202000-00007 · Cited by 1,474 · see citing works
Pathological Changes Induced in Cerebrocortical Neurons by Phencyclidine and Related Drugs
Olney, J. W., Labruyere, J., & Price, M. T. (1989) · Science · doi:10.1126/science.2660263 · Cited by 1,250 · see citing works
Self-citationStudy of a New Schizophrenomimetic Drug—Sernyl
LUBY, E. D. (1959) · Archives of Neurology And Psychiatry · doi:10.1001/archneurpsyc.1959.02340150095011 · Cited by 921 · see citing works
NMDA Antagonist Neurotoxicity: Mechanism and Prevention
Olney, J. W., Labruyere, J., Wang, G., Wozniak, D. F., Price, M. T., & Sesma, M. A. (1991) · Science · doi:10.1126/science.1835799 · Cited by 841 · see citing works
Self-citationKetamine: an update on the first twenty-five years of clinical experience
Reich, D. L., & Silvay, G. (1989) · Canadian Journal of Anesthesia/Journal canadien d anesthésie · doi:10.1007/bf03011442 · Cited by 707 · see citing works
NMDA Receptor Function and Human Cognition: The Effects of Ketamine in Healthy Volunteers
Malhotra, A. K. (1996) · Neuropsychopharmacology · doi:10.1016/0893-133x(95)00137-3 · Cited by 680 · see citing works
Ketamine-Induced NMDA Receptor Hypofunction as a Model of Memory Impairment and Psychosis
Newcomer, J. W. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(98)00067-0 · Cited by 604 · see citing works
Self-citationARCHIVES OF NEUROLOGY AND PSYCHIATRY
Mott, F. W. (1923) · The Journal of Nervous and Mental Disease · doi:10.1097/00005053-192304000-00071 · Cited by 587 · see citing works
Jakab, R. L., & Goldman-Rakic, P. S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.2.735 · Cited by 536 · see citing works
Widespread origin of the primate mesofrontal dopamine system.
Williams, S. M., & Goldman-Rakic, P. (1998) · Cerebral Cortex · doi:10.1093/cercor/8.4.321 · Cited by 481 · see citing works
Excitatory amino acid transmission
Hicks, T. P., Lodge, D., Mclennan, H., Hardy, J., & Cowburn, R. F. (1987) · FEBS Letters · doi:10.1016/0014-5793(87)80857-8 · Cited by 432 · see citing works
Adams, B. W., & Moghaddam, B. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-14-05545.1998 · Cited by 388 · see citing works
Mental Illness in Adults With Fetal Alcohol Syndrome or Fetal Alcohol Effects
Famy, C., Streissguth, A. P., & Unis, A. S. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.4.552 · Cited by 357 · see citing works
Cholinergic Hyperactivity and Negative Schizophrenic Symptoms
Tandon, R. (1989) · Archives of General Psychiatry · doi:10.1001/archpsyc.1989.01810080075010 · Cited by 354 · see citing works
Kristensen, J. D., Svensson, B. A., & Gordh, T. (1992) · Pain · doi:10.1016/0304-3959(92)90266-e · Cited by 304 · see citing works
PCP (Phencyclidine): Historical and Current Perspectives
Henderson, G. (1982) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(82)91253-6 · Cited by 263 · see citing works
Interactive effects of subanesthetic ketamine and haloperidol in healthy humans
Krystal, J. H., D’Souza, D. C., Karper, L. P., Bennett, A., Abi‐Dargham, A., Abi‐Saab, D., Cassello, K., Bowers, M. B., Vegso, S., Heninger, G. R., et al. (1999) · Psychopharmacology · doi:10.1007/s002130051049 · Cited by 243 · see citing works
Testa, C. M., Friberg, I. K., Weiss, S. W., & Standaert, D. G. (1998) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19980105)390:1 · Cited by 237 · see citing works
Benzodiazepines in the treatment of schizophrenia: a review and reappraisal
Wolkowitz, O. M., & Pickar, D. (1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.6.714 · Cited by 221 · see citing works
Farber, N. B., Wozniak, D. F., Price, M. T., Labruyere, J., Huss, J. M., Peter, H. S., & Olney, J. W. (1995) · Biological Psychiatry · doi:10.1016/0006-3223(95)00046-1 · Cited by 219 · see citing works
Self-citationD1Receptor in Interneurons of Macaque Prefrontal Cortex: Distribution and Subcellular Localization
Muly, E. C., Szigeti‐Buck, K., & Goldman‐Rakic, P. S. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-24-10553.1998 · Cited by 217 · see citing works
Grotta, J. C., Clark, W. M., Coull, B. M., Pettigrew, L. C., Mackay, B., Goldstein, L. B., Meissner, I., Murphy, D. E., & LaRue, L. (1995) · Stroke · doi:10.1161/01.str.26.4.602 · Cited by 208 · see citing works
Clozapine Blunts N-Methyl-d-Aspartate Antagonist-Induced Psychosis: A Study with Ketamine
Malhotra, A. K., Adler, C. M., Kennison, S. D., Elman, I., Pickar, D., & Breier, A. F. (1997) · Biological Psychiatry · doi:10.1016/s0006-3223(96)00546-x · Cited by 200 · see citing works
Interactive effects of subanesthetic ketamine and subhypnotic lorazepam in humans
Krystal, J. H., Karper, L. P., Bennett, A., D’Souza, D. C., Abi‐Dargham, A., Morrissey, K., Abi‐Saab, D., Bremner, J. D., Bowers, M. B., Suckow, R. F., et al. (1998) · Psychopharmacology · doi:10.1007/s002130050503 · Cited by 184 · see citing works
Effects of phencyclidine on excitatory amino acid activation of spinal interneurones in the cat
Lodge, D., & Anis, N. A. (1982) · European Journal of Pharmacology · doi:10.1016/0014-2999(82)90022-x · Cited by 158 · see citing works
Greengard, P., Nairn, A. C., Girault, J., Ouimet, C. C., Snyder, G. L., Fisone, G., Allen, P. B., Fienberg, A. A., & Nishi, A. (1998) · Brain Research Reviews · doi:10.1016/s0165-0173(97)00057-x · Cited by 153 · see citing works
Hypobaric-ischemic conditions produce glutamate-like cytopathology in infant rat brain
Ikonomidou, C., PRICE, M. T., Ogilvie, J. M., Frierdich, G. E., Labruyere, J., Salles, K., & Olney, J. W. (1989) · Journal of Neuroscience · doi:10.1523/jneurosci.09-05-01693.1989 · Cited by 147 · see citing works
Self-citationComparison of Sernyl with Other Drugs
Rosenbaum, G. (1959) · A M A Archives of General Psychiatry · doi:10.1001/archpsyc.1959.03590060113013 · Cited by 141 · see citing works
Comparison of Phencyclidine Hydrochloride (Sernyl) with Other Drugs
Cohen, B. D. (1962) · Archives of General Psychiatry · doi:10.1001/archpsyc.1962.01710230063007 · Cited by 131 · see citing works
Clinical Uses of Benzodiazepines
Hollister, L. E., Müller-Oerlinghausen, B., Rickels, K., & Shader, R. I. (1993) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-199312001-00001 · Cited by 125 · see citing works
Muscarinic cholinergic hyperactivity in schizophrenia
Tandon, R., Shipley, J. E., Greden, J. F., Mann, N. A., Eisner, W. H., & Goodson, J. A. (1991) · Schizophrenia Research · doi:10.1016/0920-9964(91)90006-d · Cited by 120 · see citing works
Diazepam Treatment of Early Signs of Exacerbation in Schizophrenia
Carpenter, W. T., Buchanan, R. W., Kirkpatrick, B. W., & Breier, A. F. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.2.299 · Cited by 117 · see citing works
Multifocal brain damage induced by phencyclidine is augmented by pilocarpine
Corso, T. D., Sesma, M. A., Tenkova, T. I., Der, T. C., Wozniak, D. F., Farber, N. B., & Olney, J. W. (1997) · Brain Research · doi:10.1016/s0006-8993(96)01347-9 · Cited by 108 · see citing works
Self-citationMK-801-induced neuronal damage in rats
Horváth, Z., Czopf, J., & Buzsáki, G. (1997) · Brain Research · doi:10.1016/s0006-8993(96)01290-5 · Cited by 101 · see citing works
Olanzapine and fluperlapine mimic clozapine in preventing MK-801 neurotoxicity
Farber, N. B., Foster, J., Duhan, N. L., & Olney, J. W. (1996) · Schizophrenia Research · doi:10.1016/0920-9964(96)00024-2 · Cited by 98 · see citing works
Self-citationAntipsychotic drugs block phencyclidine receptor-mediated neurotoxicity
Farber, N. B., Price, M. T., Labruyere, J., Nemnich, J., Peter, H. S., Wozniak, D. F., & Olney, J. W. (1993) · Biological Psychiatry · doi:10.1016/0006-3223(93)90265-f · Cited by 97 · see citing works
Self-citationCompetitive and noncompetitive NMDA antagonists induce similar limbic degeneration
Ellison, G. D. (1994) · Neuroreport · doi:10.1097/00001756-199412000-00070 · Cited by 94 · see citing works
Wozniak, D. F., Dikranian, K., Ishimaru, M., Nardi, A., Corso, T. D., Tenkova, T., Olney, J., & Fix, A. (1998) · Neurobiology of Disease · doi:10.1006/nbdi.1998.0206 · Cited by 93 · see citing works
Self-citationDissimilar patterns of degeneration in brain following four different addictive stimulants
Ellison, G. D., & Switzer, R. C. (1993) · Neuroreport · doi:10.1097/00001756-199310000-00004 · Cited by 92 · see citing works
PCP (phencyclidine), historical and current perspectives
Domino, E. F. (1981) · Medical Entomology and Zoology · Cited by 88 · see citing works
Kim, S. H., Price, M. T., Olney, J. W., & Farber, N. B. (1999) · Molecular Psychiatry · doi:10.1038/sj.mp.4000529 · Cited by 86 · see citing works
Self-citationSerotonergic Agents That Activate 5HT2A Receptors Prevent NMDA Antagonist Neurotoxicity
Farber, N. B. (1998) · Neuropsychopharmacology · doi:10.1016/s0893-133x(97)00127-9 · Cited by 68 · see citing works
Self-citationHalothane prevents MK-801 neurotoxicity in the rat cingulate cortex
Ishimaru, M. J., Fukamauchi, F., & Olney, J. W. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11650-l · Cited by 59 · see citing works
Self-citationHasegawa, M., Kinoshita, H., Amano, M., Hasegawa, T., Kameyama, T., & Nabeshima, T. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90106-u · Cited by 55 · see citing works
DUNDEE, J. W., & LILBURN, J. K. (1978) · Anaesthesia · doi:10.1111/j.1365-2044.1978.tb12413.x · Cited by 49 · see citing works
Jevtović‐Todorović, V., Kirby, C. O., & Olney, J. W. (1997) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199702000-00006 · Cited by 48 · see citing works
Self-citationα2 Adrenergic Agonists Prevent MK-801 Neurotoxicity
Farber, N. B. (1995) · Neuropsychopharmacology · doi:10.1016/0893-133x(95)00048-i · Cited by 47 · see citing works
Self-citationAcute phencyclidine (PCP) intoxication: psychopathology and prognosis.
Yesavage, J. A., & Freman, A. M. (1978) · PubMed · Cited by 45 · see citing works
Giovannini, M. G., Camilli, F., Mundula, A., & Pepeu, G. (1994) · Neurochemistry International · doi:10.1016/0197-0186(94)90048-5 · Cited by 43 · see citing works
Muir, K. W., Grosset, D. G., & Lees, K. R. (1997) · Clinical Neuropharmacology · doi:10.1097/00002826-199708000-00003 · Cited by 35 · see citing works
Fix, A. S., Wightman, K. A., & O'Callaghan, J. P. (1995) · PubMed · Cited by 26 · see citing works
d-CPPene (SDZ EAA-494)—A Competitive NMDA Antagonist
Herrling, P. L., Emre, M., & Watkins, J. C. (1997) · Elsevier eBooks · doi:10.1016/b978-012546820-6/50004-9 · Cited by 25 · see citing works
Effect of thiopentone on emergence reactions to ketamine anaesthesia
MAGBAGBEOLA, J. A. O., & Thomas, N. A. (1974) · Canadian Journal of Anesthesia/Journal canadien d anesthésie · doi:10.1007/bf03005737 · Cited by 25 · see citing works
Clinical use of the benzodiazepines.
Dj, G., & Shader, R. I. (1981) · PubMed · Cited by 15 · see citing works
[Clinical use of benzodiazepines].
Bratfos, O. (1977) · PubMed · Cited by 9 · see citing works
Flagged first, then by citations
1 of the 63 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
A default mode of brain function
Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.2.676 · Cited by 12,190 · see citing works
Glutamate receptor ion channels
Mayer, M. L. (2005) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2005.05.004 · Cited by 3,645 · see citing works
Glutamate Receptor Ion Channels: Structure, Regulation, and Function
Traynelis, S. F., Wollmuth, L. P., McBain, C. J., Menniti, F. S., Vance, K. M., Ogden, K. K., Hansen, K. B., Yuan, H., Myers, S. J., & Dingledine, R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002451 · Cited by 3,568 · see citing works
General Anesthesia, Sleep, and Coma
Brown, E. N., Lydic, R., & Schiff, N. D. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0808281 · Cited by 1,346 · see citing works
Lisman, J. E., Coyle, J. T., Green, R. W., Javitt, D. C., Benes, F. M., Heckers, S., & Grace, A. A. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.02.005 · Cited by 1,010 · see citing works
DeGiorgio, L. A., Konstantinov, K. N., Lee, S. C., Hardin, J., Volpe, B. T., & Diamond, B. (2001) · Nature Medicine · doi:10.1038/nm1101-1189 · Cited by 798 · see citing works
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686 · see citing works
Ketamine Pharmacology: An Update ( <i>Pharmacodynamics and Molecular Aspects, Recent Findings</i> )
Mion, G., & Villevieille, T. (2013) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12099 · Cited by 711 · see citing works
Neural synchrony indexes disordered perception and cognition in schizophrenia
Spencer, K., Nestor, P. G., Perlmutter, R., Niznikiewicz, M. A., Klump, M. C., Frumin, M., Shenton, M. E., & McCarley, R. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406074101 · Cited by 591 · see citing works
Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase
Behrens, M. M., Ali, S. S., Dao, D. N., Lucero, J., Shekhtman, G., Quick, K. L., & Dugan, L. L. (2007) · Science · doi:10.1126/science.1148045 · Cited by 585 · see citing works
Javitt, D. C. (2007) · International review of neurobiology · doi:10.1016/s0074-7742(06)78003-5 · Cited by 563 · see citing works
The dysconnection hypothesis (2016)
Friston, K., Brown, H. R., Siemerkus, J., & Stephan, K. E. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.07.014 · Cited by 561 · see citing works
General Anesthesia and Altered States of Arousal: A Systems Neuroscience Analysis
Brown, E. N., Purdon, P. L., & Dort, C. J. V. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153200 · Cited by 551 · see citing works
Regulation of affect by the lateral septum: implications for neuropsychiatry
Sheehan, T. P., Chambers, R. A., & Russell, D. S. (2004) · Brain Research Reviews · doi:10.1016/j.brainresrev.2004.04.009 · Cited by 514 · see citing works
Neill, J. C., Barnes, S. A., Cook, S., Grayson, B., Idris, N. F., McLean, S. L., Snigdha, S., Rajagopal, L., & Harte, M. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.07.004 · Cited by 525 · see citing works
Glutamate as a therapeutic target in psychiatric disorders
Javitt, D. C. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001551 · Cited by 524 · see citing works
Multimodal General Anesthesia: Theory and Practice
Brown, E. N., Pavone, K. J., & Naranjo, M. (2018) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000003668 · Cited by 522 · see citing works
Anti-NMDA receptor encephalitis in Japan
Iizuka, T., Sakai, F., Ide, T., Monzen, T., Yoshii, S., Iigaya, M., Suzuki, K., Lynch, D. R., Suzuki, N., Hata, T., et al. (2007) · Neurology · doi:10.1212/01.wnl.0000278388.90370.c3 · Cited by 517 · see citing works
Lee, K.-H., Williams, L. M., Breakspear, M. J., & Gordon, E. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(02)00220-5 · Cited by 479 · 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
Oxidative stress in schizophrenia: An integrated approach
Bitanihirwe, B. K. Y., & Woo, T.-U. W. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.10.008 · Cited by 474 · 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
The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia
Na, K., Jung, H., & Kim, Y. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.10.022 · Cited by 425 · see citing works
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
Lisman, J. E., & Otmakhova, N. A. (2001) · Hippocampus · doi:10.1002/hipo.1071 · Cited by 402 · see citing works
Motor Symptoms and Schizophrenia
Walther, S., & Strik, W. K. (2012) · Neuropsychobiology · doi:10.1159/000339456 · Cited by 367 · see citing works
Epidemiology-driven neurodevelopmental animal models of schizophrenia
Meyer, U., & Feldon, J. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.10.018 · Cited by 366 · see citing works
Acute mechanisms underlying antibody effects in anti–N‐methyl‐D‐aspartate receptor encephalitis
Moscato, E. H., Peng, X., Jain, A., Parsons, T. D., Dalmau, J. O., & Balice‐Gordon, R. J. (2014) · Annals of Neurology · doi:10.1002/ana.24195 · Cited by 361 · see citing works
Physiological functions of D-amino acid oxidases: from yeast to humans
Pollegioni, L., Piubelli, L., Sacchi, S., Pilone, M. S., & Molla, G. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-6558-4 · Cited by 360 · see citing works
Review: Glutamate and dopamine dysregulation in schizophrenia — a synthesis and selective review
Stone, J., Morrison, P., & Pilowsky, L. (2007) · Journal of Psychopharmacology · doi:10.1177/0269881106073126 · Cited by 392 · 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
Ketamine-induced changes in rat behaviour: A possible animal model of schizophrenia
Becker, A., Peters, B., Schröeder, H., Mann, T., Huether, G., & Grecksch, G. (2003) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(03)00080-0 · Cited by 339 · see citing works
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
Pinault, D. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.10.006 · Cited by 315 · see citing works
Reviewing the ketamine model for schizophrenia
Frohlich, J., & Van Horn, J. D. (2014) · Journal of Psychopharmacology · doi:10.1177/0269881113512909 · Cited by 303 · see citing works
López-Figueroa, A. L., Norton, C. S., López-Figueroa, M. O., Armellini-Dodel, D., Burke, S., Akil, H., López, J. F., & Watson, S. J. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2003.09.017 · Cited by 296 · see citing works
Kinney, G. G., O’Brien, J. A., Lemaire, W., Burno, M., Bickel, D. J., Clements, M. K., Chen, T., Wisnoski, D. D., Lindsley, C. W., Tiller, P. R., et al. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.079244 · Cited by 298 · see citing works
Mauney, S. A., Athanas, K. M., Pantazopoulos, H., Shaskan, N., Passeri, E., Berretta, S., & Woo, T.-U. W. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.05.007 · Cited by 291 · see citing works
The cognitive neuroscience of schizophrenia.
Barch, D. M. (2005) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.1.102803.143959 · Cited by 437 · see citing works
Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis
Gable, M., Gavali, S. S., Radner, A. B., Tilley, D. H., Lee, B., Dyner, L., Collins, A. R., Dengel, A., Dalmau, J. O., & Glaser, C. A. (2009) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-009-0799-0 · Cited by 289 · 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
New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis
Yang, A. C., & Tsai, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18081689 · Cited by 286 · see citing works
Phenothiazine: the seven lives of pharmacology's first lead structure
Ohlow, M. J., & Moosmann, B. (2011) · Drug Discovery Today · doi:10.1016/j.drudis.2011.01.001 · Cited by 283 · see citing works
Thakkar, K. N., Nichols, H. S., McIntosh, L. G., & Park, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027089 · Cited by 264 · see citing works
Gandal, M. J., Edgar, J. C., Klook, K., & Siegel, S. J. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.02.007 · Cited by 269 · see citing works
Krystal, J. H., Abi-Saab, W., Perry, E., D’Souza, D. C., Liu, N., Gueorguieva, R., McDougall, L., Hunsberger, T., Belger, A., Levine, L., et al. (2005) · Psychopharmacology · doi:10.1007/s00213-004-1982-8 · Cited by 272 · see citing works
Novel Neurotransmitters and Their Neuropsychiatric Relevance
Snyder, S. H., & Ferris, C. D. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.11.1738 · Cited by 262 · see citing works
Hippocampal modulation of sensorimotor processes.
Bast, T., & Feldon, J. (2003) · Progress in neurobiology · doi:10.1016/s0301-0082(03)00112-6 · Cited by 267 · see citing works
Red Flags: Clinical Signs for Identifying Autoimmune Encephalitis in Psychiatric Patients
Herken, J., & Prüß, H. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00025 · Cited by 255 · see citing works
The thalamus and schizophrenia: current status of research
Byne, W. M., Hazlett, E. A., Buchsbaum, M. S., & Kemether, E. M. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0404-0 · Cited by 250 · see citing works
Amantadine Inhibits NMDA Receptors by Accelerating Channel Closure during Channel Block
Blanpied, T. A., Clarke, R. J., & Johnson, J. W. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4262-04.2005 · Cited by 248 · see citing works
Kokkinou, M., Ashok, A., & Howes, O. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.190 · Cited by 212 · see citing works
Journey through the K-hole: Phenomenological aspects of ketamine use
Muetzelfeldt, L., Kamboj, S. K., Rees, H., Taylor, J., Morgan, C. J. A., & Curran, H. V. (2008) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2008.01.024 · Cited by 246 · see citing works
Grayson, B., Idris, N. F., & Neill, J. C. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.06.012 · Cited by 243 · see citing works
Serine racemase is predominantly localized in neurons in mouse brain
Miya, K., Inoue, R., Takata, Y., Abe, M., Natsume, R., Sakimura, K., Hongou, K., Miyawaki, T., & Mori, H. (2008) · The Journal of Comparative Neurology · doi:10.1002/cne.21822 · Cited by 243 · see citing works
Interleukin-6 Mediates the Increase in NADPH-Oxidase in the Ketamine Model of Schizophrenia
Behrens, M. M., Ali, S. S., & Dugan, L. L. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4457-08.2008 · Cited by 241 · see citing works
NMDA hypofunction as a convergence point for progression and symptoms of schizophrenia
Snyder, M. A., & Gao, W. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00031 · Cited by 237 · see citing works
Cochran, S. M., Kennedy, M., McKerchar, C. E., Steward, L. J., Pratt, J. A., & MORRIS, B. J. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300031 · Cited by 236 · see citing works
Schizophrenia and Oxidative Stress: Glutamate Cysteine Ligase Modifier as a Susceptibility Gene
Tosic, M., Ott, J., Barral, S., Bovet, P., Deppen, P., Gheorghita, F., Matthey, M.-L., Parnas, J., Preisig, M., Saraga, M., et al. (2006) · The American Journal of Human Genetics · doi:10.1086/507566 · Cited by 234 · see citing works
Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms
Inserra, A., De Gregorio, D., & Gobbi, G. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000056 · Cited by 232 · see citing works
Variable Global Dysconnectivity and Individual Differences in Schizophrenia
Cole, M. W., Anticevic, A., Repovš, G., & Barch, D. M. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.02.010 · Cited by 227 · see citing works
Hakami, T. M., Jones, N. C., Tolmacheva, E. A., Gaudias, J., Chaumont, J., Salzberg, M. R., O'Brien, T. J., & Pinault, D. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006755 · Cited by 222 · see citing works
Molecular Targets for Treating Cognitive Dysfunction in Schizophrenia
Gray, J. A., & Roth, B. L. (2007) · Schizophrenia Bulletin · doi:10.1093/schbul/sbm074 · Cited by 225 · see citing works
Glial transporters for glutamate, glycine and GABA I. Glutamate transporters
Gadea, A., & López-Colomé, A. M. (2001) · Journal of Neuroscience Research · doi:10.1002/jnr.1039 · Cited by 227 · see citing works
Mouchlianitis, E. D., Bloomfield, M., Law, V., Beck, K., Selvaraj, S., Rasquinha, N., Waldman, A. D., Turkheimer, F., Egerton, A., Stone, J. M., et al. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbv151 · Cited by 226 · see citing works
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
Lieberman, J. A., Bymaster, F. P., Meltzer, H. Y., Deutch, A. Y., Duncan, G. E., Marx, C. E., Aprille, J. R., Dwyer, D. S., Li, X., Mahadik, S. P., et al. (2008) · Pharmacological Reviews · doi:10.1124/pr.107.00107 · Cited by 223 · see citing works
Kinney, G. G., Burno, M., Campbell, U. C., Hernández, L. M., Rodriguez, D. E., Bristow, L. J., & Conn, P. J. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.048702 · Cited by 219 · see citing works
Lodge, D. J., & Grace, A. A. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.01.031 · Cited by 215 · see citing works
Freedman, R., Adams, C. E., & Leonard, S. S. (2000) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(00)00109-5 · Cited by 212 · see citing works
The Role of Amino Acids in Neurotransmission and Fluorescent Tools for Their Detection
Dalangin, R., Kim, A., & Campbell, R. E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176197 · Cited by 211 · see citing works
Tatti, R., Haley, M. S., Swanson, O. K., Tselha, T., & Maffei, A. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.09.017 · Cited by 211 · see citing works
Abdul-Monim, Z., Neill, J. C., & Reynolds, G. P. (2007) · Journal of Psychopharmacology · doi:10.1177/0269881107067097 · Cited by 206 · see citing works
Konradi, C. L., & Heckers, S. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01267-7 · Cited by 200 · see citing works
Rajkowska, G., Miguel-Hidalgo, J. J., Makkos, Z., Meltzer, H. Y., Overholser, J. C., & Stockmeier, C. A. (2002) · Schizophrenia Research · doi:10.1016/s0920-9964(02)00339-0 · Cited by 196 · see citing works
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
Wnt Signaling: Role in Alzheimer Disease and Schizophrenia
Inestrosa, N. C., Montecinos-Oliva, C., & Fuenzalida, M. (2012) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-012-9417-5 · Cited by 186 · see citing works
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
Anti-NMDA Receptor Encephalitis in Psychiatry
Kayser, M. S., & Dalmau, J. O. (2011) · Current Psychiatry Reviews · doi:10.2174/157340011797183184 · Cited by 185 · see citing works
Unique Effects of Clozapine: A Pharmacological Perspective
Khokhar, J. Y., Henricks, A. M., Sullivan, E. D. K., & Green, A. I. (2018) · Advances in pharmacology · doi:10.1016/bs.apha.2017.09.009 · Cited by 185 · see citing works
The acute effects of NMDA antagonism: from the rodent to the human brain.
Gunduz-Bruce, H. (2009) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.07.006 · Cited by 182 · see citing works
Wiedholz, L. M., Owens, W. A., Horton, R. E., Feyder, M. J., Karlsson, R.-M., Hefner, K. R., Sprengel, R., Celikel, T., Daws, L. C., & Holmes, A. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4002056 · Cited by 180 · see citing works
Clinton, S. M., & Meador‐Woodruff, J. H. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300451 · Cited by 177 · see citing works
Black, M. D. (2005) · Psychopharmacology · doi:10.1007/s00213-004-2065-6 · Cited by 176 · see citing works
Calcium signaling dysfunction in schizophrenia: a unifying approach
Lidow, M. S. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(03)00203-0 · Cited by 173 · see citing works
Steullet, P., Neijt, H. C., Cuénod, M., & Do, K. Q. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2005.10.014 · Cited by 173 · see citing works
The neuregulin signaling pathway and schizophrenia: From genes to synapses and neural circuits
Buonanno, A. (2010) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2010.07.012 · Cited by 172 · see citing works
Karasawa, J.-I., Hashimoto, K., & Chaki, S. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.07.033 · Cited by 172 · see citing works
Kinney, G. G., Sur, C., Burno, M., Mallorga, P. J., Williams, J. B., Figueroa, D. J., Wittmann, M., Lemaire, W., & Conn, P. J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-20-07586.2003 · Cited by 172 · see citing works
Influence of the NR3A subunit on NMDA receptor functions
Henson, M. A., Roberts, A. C., Pérez‐Otaño, I., & Philpot, B. D. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.01.004 · Cited by 170 · see citing works
Lindsley, C. W., Wisnoski, D. D., Leister, W., O’Brien, J. A., Lemaire, W., David L. Williams, Burno, M., Sur, C., Kinney, G. G., Pettibone, D. J., et al. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm049400d · Cited by 170 · see citing works
ALX 5407: A Potent, Selective Inhibitor of the hGlyT1 Glycine Transporter
Atkinson, B. N., Bell, S. C., Vivo, M. D., Kowalski, L. R., Lechner, S. M., Ognyanov, V. I., Tham, C., Tsai, C., Jia, J., Ashton, D. J., et al. (2001) · Molecular Pharmacology · doi:10.1124/mol.60.6.1414 · Cited by 169 · see citing works
Downregulation of Parvalbumin at Cortical GABA Synapses Reduces Network Gamma Oscillatory Activity
Volman, V., Behrens, M. M., & Sejnowski, T. J. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3041-11.2011 · Cited by 164 · see citing works
Powell, S. B., Sejnowski, T. J., & Behrens, M. M. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.01.049 · Cited by 164 · see citing works
The Neural Circuits Underlying General Anesthesia and Sleep
Moody, O. A., Zhang, E. R., Vincent, K. F., Kato, R., Melonakos, E. D., Nehs, C. J., & Solt, K. (2021) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000005361 · Cited by 165 · see citing works
"Gamma (40 Hz) phase synchronicity" and symptom dimensions in schizophrenia
Lee, K.-H., Williams, L. M., Haig, A. R., & Gordon, E. (2003) · Cognitive Neuropsychiatry · doi:10.1080/713752240 · Cited by 168 · see citing works
Webster, J. P., Kaushik, M., Bristow, G. C., & McConkey, G. A. (2012) · Journal of Experimental Biology · doi:10.1242/jeb.074716 · Cited by 168 · see citing works
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
Sarcosine (N-Methylglycine) Treatment for Acute Schizophrenia: A Randomized, Double-Blind Study
Lane, H., Liu, Y., Huang, C., Chang, Y., Liau, C.-H., Perng, C., & Tsai, G. E. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.04.038 · Cited by 164 · see citing works
- Authors
- Olney, J. W., Newcomer, J. W., & Farber, N. B.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Olney, John W
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 1999-11
- Volume
- 33
- Issue
- 6
- Pages
- 523-533
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2084120702
- Cited by
- 1,020
- References
- 63
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 25 · 2023: 23 · 2022: 24 · 2021: 30 · 2020: 32 · 2019: 33 · 2018: 28 · 2017: 46 · 2016: 29 · 2015: 50 · 2014: 56 · 2013: 38 · 2012: 55
- FWCI
- 11.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k02mh001510-05, 5k20da000290-05)
- National Institute of Mental Health (MH33894, MH-01510)
- National Institute on Drug Abuse (DA00290)
- 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 › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, NMDA receptor hypofunction, phencyclidine, NMDA receptor antagonists, neurotoxicity, psychotomimetic effects, schizophrenia treatment
- MeSH terms
- Animals, Disease Models, Animal, Enzyme Inhibitors, Humans, Models, Biological, Models, Psychological, Phencyclidine, Schizophrenia, Receptors, N-Methyl-D-Aspartate, Rats
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