Imaging glutamate in schizophrenia: review of findings and implications for drug discovery
Abstract
Currently, all treatments for schizophrenia (SCZ) function primarily by blocking D(2)-type dopamine receptors. Given the limitations of these medications, substantial efforts have been made to identify alternative neurochemical targets for treatment development in SCZ. One such target is brain glutamate. The objective of this article is to review and synthesize the proton magnetic resonance spectroscopy ((1)H MRS) and positron emission tomography (PET)/single-photon emission computed tomography (SPECT) investigations that have examined glutamatergic indices in SCZ, including those of modulatory compounds such as glutathione (GSH) and glycine, as well as data from ketamine challenge studies. The reviewed (1)H MRS and PET/SPECT studies support the theory of hypofunction of the N-methyl-D-aspartate receptor (NMDAR) in SCZ, as well as the convergence between the dopamine and glutamate models of SCZ. We also review several advances in MRS and PET technologies that have opened the door for new opportunities to investigate the glutamate system in SCZ and discuss some ways in which these imaging tools can be used to facilitate a greater understanding of the glutamate system in SCZ and the successful and efficient development of new glutamate-based treatments for SCZ.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Trials of drugs aimed at glutamatergic, immune, or antioxidant targets have yielded mixed findings, some encouraging and others inconclusive.
“To date, clinical trials using molecules targeting either the glutamatergic system (mGluR5, mGluR2/3, glycine site of NMDARs) (Javitt, 2012; Kantrowitz and Javitt, 2012; Poels et al., 2014; Vinson and Conn, 2012), the immune (Leza et al., 2014; Muller et al., 2013), or antioxidant systems (Leza et al., 2014; Reddy and Reddy, 2011) have produced mixed results, some encouraging and others inconclusi”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Poels et al., 2014
Glu concentration abnormalities exist in schizophrenia relative to healthy controls.
“Studies show Glu concentration abnormalities in SCZ relative to healthy controls, 49,50”
From Are hallucinations due to an imbalance between excitatory and inhibitory influences on the brain? (2016) · cites this paper as [49]
Cites
Implications of Normal Brain Development for the Pathogenesis of Schizophrenia
Weinberger, D. R. (1987) · Archives of General Psychiatry · doi:10.1001/archpsyc.1987.01800190080012 · Cited by 3,724 · 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
Dopamine in schizophrenia: a review and reconceptualization
Davis, K. L., Kahn, R. S., Ko, G., & Davidson, M. (1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.11.1474 · Cited by 2,021 · see citing works
Consensus Nomenclature for <i>in vivo</i> Imaging of Reversibly Binding Radioligands
Innis, R. B., Cunningham, V. J., Delforge, J., Fujita, M., Gjedde, A., Gunn, R. N., Holden, J., Houle, S., Huang, S.-C., Ichise, M., et al. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600493 · Cited by 1,955 · see citing works
Self-citationLaruelle, M., Abi-Dargham, A., van Dyck, C. H., Gil, R., D'Souza, C. D., Erdos, J., McCance, E., Rosenblatt, W., Fingado, C., Zoghbi, S. S., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.17.9235 · Cited by 1,291 · see citing works
Self-citationBreier, A., Su, T.-P., Saunders, R., Carson, R. E., Kolachana, B. S., de Bartolomeis, A., Weinberger, D. R., Weisenfeld, N., Malhotra, A. K., Eckelman, W. C., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.6.2569 · Cited by 1,154 · see citing works
Kapur, S., Zipursky, R., Jones, C., Remington, G., & Houle, S. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.4.514 · Cited by 1,090 · see citing works
Coupling of mGluR/Homer and PSD-95 Complexes by the Shank Family of Postsynaptic Density Proteins
Tu, J. C., Xiao, B., Naisbitt, S. R., Yuan, J. P., Petralia, R. S., Brakeman, P., Doan, A., Aakalu, V. K., Lanahan, A. A., Sheng, M., et al. (1999) · Neuron · doi:10.1016/s0896-6273(00)80810-7 · Cited by 1,047 · see citing works
Increased baseline occupancy of D <sub>2</sub> 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
Self-citationNaisbitt, S., Kim, E., Tu, J. C., Xiao, B., Sala, C., Valtschanoff, J., Weinberg, R. J., Worley, P. F., & Sheng, M. (1999) · Neuron · doi:10.1016/s0896-6273(00)80809-0 · Cited by 1,009 · see citing works
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
Self-citationIncreased striatal dopamine transmission in schizophrenia: confirmation in a second cohort.
Abi-Dargham, A., Gil, R. B., Krystal, J., Baldwin, R., Seibyl, J., Bowers, M., van Dyck, C., Charney, D., Innis, R., & Laruelle, M. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.6.761 · Cited by 860 · see citing works
Self-citationPrefrontal Dopamine D<sub>1</sub>Receptors and Working Memory in Schizophrenia
Abi-Dargham, A., Mawlawi, O., Lombardo, I., Gil, R., Martinez, D., Huang, Y., Hwang, D.-R., Keilp, J., Kochan, L., Van Heertum, R., et al. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03708.2002 · Cited by 724 · see citing works
Self-citationN-Acetylcysteine—a safe antidote for cysteine/glutathione deficiency
Atkuri, K. R., Mantovani, J. J., Herzenberg, L. A., & Herzenberg, L. A. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.04.005 · Cited by 721 · see citing works
Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET
Okubo, Y., Suhara, T., Suzuki, K., Kobayashi, K., Inoue, O., Terasaki, O., Someya, Y., Sassa, T., Sudo, Y., Matsushima, E., et al. (1997) · Nature · doi:10.1038/385634a0 · Cited by 710 · see citing works
Malhotra, A. K. (1997) · Neuropsychopharmacology · doi:10.1016/s0893-133x(97)00036-5 · Cited by 681 · see citing works
Effects of Ketamine in Normal and Schizophrenic Volunteers
Lahti, A. C. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00243-3 · Cited by 674 · see citing works
Metabotropic glutamate receptors
Ferraguti, F., & Shigemoto, R. (2006) · Cell and Tissue Research · doi:10.1007/s00441-006-0266-5 · Cited by 647 · see citing works
Lu, Y.-M., Jia, Z., Janus, C., Henderson, J. T., Gerlai, R., Wojtowicz, J. M., & Roder, J. C. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-13-05196.1997 · Cited by 634 · see citing works
Miyamoto, S., Miyake, N., Jarskog, L. F., Fleischhacker, W. W., & Lieberman, J. A. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.47 · Cited by 576 · see citing works
Self-citationBerk, 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
Provocative tests with psychostimulant drugs in schizophrenia
Lieberman, J. A., Kane, J. M., & Alvir, J. (1987) · Psychopharmacology · doi:10.1007/bf00216006 · Cited by 535 · see citing works
Self-citationNordström, A., Farde, L., Wiesel, F., Forslund, K., Pauli, S., Halldin, C., & Uppfeldt, G. (1993) · Biological Psychiatry · doi:10.1016/0006-3223(93)90288-o · Cited by 527 · 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
Self-citationDean, O., Giorlando, F., & Berk, M. (2011) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.100057 · Cited by 494 · see citing works
Kegeles, L., Abi-Dargham, A., Zea-Ponce, Y., Rodenhiser-Hill, J., Mann, J., Heertum, R. V. V., Cooper, T. B., Carlsson, A., & Laruelle, M. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(00)00976-8 · Cited by 425 · see citing works
Self-citationAbi‐Dargham, A., Krystal, J. H., Anjilvel, S., Scanley, B. E., Zoghbi, S. S., Baldwin, R. M., Rajeevan, N., Ellis, S. P., Petrakis, I. L., Seibyl, J. P., et al. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.11.1550 · Cited by 405 · see citing works
Self-citationThéberge, J., Bartha, R., Drost, D. J., Menon, R. S., MALLA, A. K., Takhar, J., Neufeld, R. W. J., Rogers, J. S., Pavlosky, W. F., Schaefer, B., et al. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.11.1944 · Cited by 398 · see citing works
Kantrowitz, J. T., & Javitt, D. C. (2010) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2010.04.006 · Cited by 397 · see citing works
Self-citationElevated dopa decarboxylase activity in living brain of patients with psychosis
Reith, J., Benkelfat, C., Sherwin, A., Yasuhara, Y., Kuwabara, H., Andermann, F., Bachneff, S., Cumming, P., Diksic, M., & Dyve, S. E. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.24.11651 · Cited by 342 · see citing works
Adler, C. M., Malhotra, A. K., Elman, I., Goldberg, T. E., Egan, M. F., Pickar, D., & Breier, A. F. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.10.1646 · Cited by 337 · see citing works
Presynaptic dopamine function in striatum of neuroleptic-naive schizophrenic patients
Hietala, J. A., Syvälahti, E. K. G., Kuoppamäki, M., Hietala, J., Syvälahti, E. K. G., Haaparanta‐Solin, M., Kuoppamäki, M., Ruotsalainen, U., Vuorio, K. A., Räkköläinen, V., et al. (1995) · The Lancet · doi:10.1016/s0140-6736(95)91801-9 · Cited by 321 · see citing works
Pisani, A., Gubellini, P., Bonsi, P., Conquet, F., Picconi, B., Centonze, D., Bernardi, G., & Calabresi, P. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00297-4 · Cited by 311 · see citing works
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
Mao, X. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.1519 · Cited by 296 · see citing works
Stone, J. M., Dietrich, C., Edden, R., Mehta, M. A., De Simoni, S., Reed, L. J., Krystal, J. H., Nutt, D., & Barker, G. J. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.171 · Cited by 295 · see citing works
First in vivo evidence of an NMDA receptor deficit in medication-free schizophrenic patients
Pilowsky, L. S., Bressan, R. A., Stone, J. M., Erlandsson, K., Mulligan, R. S., Krystal, J. H., & Ell, P. J. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001751 · Cited by 278 · see citing works
Deschwanden, A., Karolewicz, B., Feyissa, A. M., Treyer, V., Ametamey, S. M., Johayem, A., Burger, C., Auberson, Y. P., Sovago, J., Stockmeier, C. A., et al. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.09111607 · Cited by 278 · see citing works
Abnormal Glutamatergic Neurotransmission and Neuronal-Glial Interactions in Acute Mania
Öngür, D., Jensen, J. E., Prescot, A. P., Stork, C., Lundy, M. Y., Cohen, B. M., & Renshaw, P. F. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.05.014 · Cited by 272 · see citing works
MODEL PSYCHOSES AND SCHIZOPHRENIA
Luby, E. D., Gottlieb, J. S., Cohen, B. D., Rosenbaum, G., & Domino, E. F. (1962) · American Journal of Psychiatry · doi:10.1176/ajp.119.1.61 · Cited by 268 · see citing works
Kinon, B. J., Zhang, L., Millen, B. A., Osuntokun, O. O., Williams, J. E., Kollack-Walker, S., Jackson, K., Kryzhanovskaya, L., & Jarkova, N. (2011) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318218dcd5 · Cited by 256 · see citing works
NMDA receptor channels: Subunit-specific potentiation by reducing agents
Köhr, G., Eckardt, S., Lüddens, H., Monyer, H., & Seeburg, P. H. (1994) · Neuron · doi:10.1016/0896-6273(94)90311-5 · Cited by 255 · see citing works
McGowan, S., Lawrence, A., Sales, T., Quested, D., & Grasby, P. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.2.134 · Cited by 251 · see citing works
de la Fuente-Sandoval, C., León-Ortíz, P., Favila, R., Stephano, S., Mamo, D., Ramírez-Bermúdez, J., & Graff-Guerrero, A. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.65 · Cited by 248 · see citing works
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
Bartha, R. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830220085012 · Cited by 230 · see citing works
Breier, A., Adler, C. M., Weisenfeld, N., Su, T.-P., Elman, I., Picken, L., Malhotra, A. K., & Pickar, D. (1998) · Synapse · doi:10.1002/(sici)1098-2396(199806)29:2 · Cited by 226 · see citing works
Vollenweider, F. X., Vontobel, P., Øye, I., Hell, D., & Leenders, K. L. (2000) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(99)00031-x · 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
Ayala, J. E., Chen, Y., Banko, J. L., Sheffler, D. J., Williams, R. D., Telk, A. N., Watson, N. L., Xiang, Z., Zhang, Y., Jones, P. J., et al. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.30 · Cited by 206 · see citing works
Matsuzawa, D., Obata, T., Shirayama, Y., Nonaka, H., Kanazawa, Y., Yoshitome, E., Takanashi, J., Matsuda, T., Shimizu, E., Ikehira, H., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001944 · Cited by 201 · see citing works
G Smith, P. D. (1998) · Neuropsychopharmacology · doi:10.1016/s0893-133x(97)00092-4 · Cited by 201 · see citing works
Meta-Analysis of the Efficacy of Adjunctive NMDA Receptor Modulators in Chronic Schizophrenia
Singh, S. P., & Singh, V. (2011) · CNS Drugs · doi:10.2165/11586650-000000000-00000 · Cited by 194 · see citing works
Uslaner, J. M., Parmentier‐Batteur, S., Flick, R. B., Surles, N. O., Lam, J. S. H., McNaughton, C. H., Jacobson, M. A., & Hutson, P. H. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.07.022 · Cited by 193 · 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
Ametamey, S. M., Kessler, L. J., Honer, M., Wyss, M. T., Buck, A., Hintermann, S., Auberson, Y. P., Gasparini, F., & Schubiger, P. A. (2006) · PubMed · Cited by 183 · see citing works
Liu, F., Grauer, S. M., Kelley, C., Navarra, R. L., Graf, R., Zhang, G., Atkinson, P. J., Popiolek, M., Wantuch, C., Khawaja, X. Z., et al. (2008) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.136580 · Cited by 183 · see citing works
de la Fuente‐Sandoval, C., León-Ortíz, P., Azcárraga, M., Stephano, S., Favila, R., Díaz-Galvis, L., Alvarado-Alanis, P., Ramírez‐Bermúdez, J., & Graff‐Guerrero, A. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.289 · Cited by 181 · 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
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
PET Study of D1 Dopamine Receptor Binding in Neuroleptic-Naive Patients With Schizophrenia
Karlsson, P., Farde, L., Halldin, C., & Sedvall, G. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.5.761 · Cited by 172 · see citing works
Altered Prefrontal Dopaminergic Function in Chronic Recreational Ketamine Users
Narendran, R., Frankle, W. G., Keefe, R. S. E., Gil, R. B., Martínez, D., Slifstein, M., Kegeles, L. S., Talbot, P. S., Huang, Y. H., Hwang, D., et al. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.12.2352 · Cited by 170 · see citing works
Self-citationTranslating Glutamate: From Pathophysiology to Treatment
Javitt, D. C., Schoepp, D., Kalivas, P. W., Volkow, N. D., Zarate, C., Merchant, K., Bear, M. F., Umbricht, D., Hajos, M., Potter, W. Z., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002804 · Cited by 168 · see citing works
Self-citationEgerton, A., Brugger, S. P., Raffin, M., Barker, G. J., Lythgoe, D. J., McGuire, P. K., & Stone, J. M. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.113 · Cited by 168 · see citing works
van Elst, L. T., Valerius, G., Büchert, M., Thiel, T., Rüsch, N., Bubl, E., Hennig, J., Ebert, D., & Olbrich, H. M. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.04.041 · Cited by 164 · 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
Miller, D. W., & Abercrombie, E. D. (1996) · Brain Research Bulletin · doi:10.1016/0361-9230(95)02144-2 · Cited by 146 · see citing works
Henry, S. (2002) · Neuropharmacology · doi:10.1016/s0028-3908(02)00332-5 · Cited by 145 · see citing works
White Matter Alterations in Deficit Schizophrenia
Rowland, L. M., Spieker, E. A., Francis, A., Barker, P. B., Carpenter, W. T., & Buchanan, R. W. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.207 · Cited by 144 · see citing works
Pinard, E., Alanine, A. I., Alberati, D., Bender, M., Borroni, E., Bourdeaux, P., Brom, V., Burner, S., Fischer, H., Hainzl, D., et al. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100210p · Cited by 135 · see citing works
das Neves Duarte, J. M., Kulak, A., Gholam-Razaee, M. M., Cuenod, M., Gruetter, R., & Do, K. Q. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.07.035 · Cited by 124 · see citing works
Assessments of Function and Biochemistry of the Anterior Cingulate Cortex in Schizophrenia
Reid, M. A., Stoeckel, L. E., White, D. M., Avsar, K. B., Bolding, M., Akella, N. S., Knowlton, R. C., den Hollander, J. A., & Lahti, A. C. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.04.013 · Cited by 122 · see citing works
Abi‐Dargham, A., Xu, X., Thompson, J. L., Gil, R. B., Kegeles, L. S., Urban, N., Narendran, R., Hwang, D., Laruelle, M. A., & Slifstein, M. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881111409265 · Cited by 120 · see citing works
Self-citationFusar‐Poli, P. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.46 · Cited by 117 · see citing works
Ohrmann, P., Siegmund, A., Suslow, T., Pedersen, A., Spitzberg, K., Kersting, A., Rothermundt, M., Arolt, V., Heindel, W., & Pfleiderer, B. (2007) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2006.07.002 · Cited by 116 · see citing works
Contribution of Cystine–Glutamate Antiporters to the Psychotomimetic Effects of Phencyclidine
Baker, D. L., Madayag, A., Kristiansen, L. V., Meador‐Woodruff, J. H., Haroutunian, V. H., & Raju, I. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301532 · Cited by 112 · see citing works
Tayoshi, S., Sumitani, S., Taniguchi, K., Shibuya‐Tayoshi, S., Numata, S., Iga, J., Nakataki, M., Ueno, S., Harada, M., & Ohmori, T. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.11.014 · Cited by 111 · see citing works
NMDA antagonist effects on striatal dopamine release: Positron emission tomography studies in humans
Kegeles, L., Martinez, D., Kochan, L., Hwang, D., Huang, Y., Mawlawi, O., Suckow, R., Heertum, R. V. V., & Laruelle, M. (2002) · Synapse · doi:10.1002/syn.10010 · Cited by 106 · see citing works
Self-citationMedial temporal lobe glutathione concentration in first episode psychosis: A 1H-MRS investigation
Wood, S. J., Berger, G. E., Wellard, R. M., Proffitt, T., McConchie, M., Berk, M., McGorry, P. D., & Pantelis, C. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.11.018 · Cited by 105 · see citing works
Grey matter and social functioning correlates of glutamatergic metabolite loss in schizophrenia
Aoyama, N., Théberge, J., Drost, D. J., Manchanda, R., Northcott, S., Neufeld, R. W. J., Menon, R. S., Rajakumar, N., Pavlosky, W. F., Densmore, M., et al. (2011) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.110.079608 · Cited by 105 · see citing works
Wong, D. F., Waterhouse, R. N., Kuwabara, H., Kim, J., Brašić, J. R., Chamroonrat, W., Stabins, M., Holt, D. P., Dannals, R. F., Hamill, T. G., et al. (2013) · Journal of Nuclear Medicine · doi:10.2967/jnumed.112.107995 · Cited by 105 · see citing works
Stone, J. M., Erlandsson, K., Arstad, E., Squassante, L., Teneggi, V., Bressan, R. A., Krystal, J. H., Ell, P. J., & Pilowsky, L. S. (2008) · Psychopharmacology · doi:10.1007/s00213-007-1047-x · Cited by 103 · see citing works
Chang, L., Friedman, J. I., Ernst, T., Zhong, K., Tsopelas, N. D., & Davis, K. L. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.05.025 · Cited by 101 · see citing works
Ohrmann, P., Siegmund, A., Suslow, T., Spitzberg, K., Kersting, A., Arolt, V., Heindel, W. L., & Pfleiderer, B. (2004) · Schizophrenia Research · doi:10.1016/j.schres.2004.08.021 · Cited by 100 · see citing works
An In Vivo Proton Magnetic Resonance Spectroscopy Study of Schizophrenia Patients
Stanley, J. A., Williamson, P., Drost, D. J., Rylett, R. J., Carr, T. J., MALLA, A. K., & Thompson, R. T. (1996) · Schizophrenia Bulletin · doi:10.1093/schbul/22.4.597 · Cited by 98 · see citing works
Olbrich, H. M., Valerius, G., Rüsch, N., Büchert, M., Thiel, T., Hennig, J., Ebert, D., & van Elst, L. T. (2008) · The World Journal of Biological Psychiatry · doi:10.1080/15622970701227811 · Cited by 96 · see citing works
Cortical glutamate–dopamine interaction and ketamine-induced psychotic symptoms in man
Aalto, S., Ihalainen, J. A., Hirvonen, J., Kajander, J., Scheinin, H., Tanila, H., Någren, K., Vilkman, H., Gustafsson, L. L., Syvälahti, E. K. G., et al. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0092-6 · Cited by 95 · see citing works
Terpstra, M., Vaughan, T. J., Uǧurbil, K., Lim, K. O., Schulz, S. C., & Rolf Gruetter, A. (2005) · Magnetic Resonance Materials in Physics Biology and Medicine · doi:10.1007/s10334-005-0012-0 · Cited by 95 · see citing works
Bustillo, J., Chen, H., Gasparovic, C., Mullins, P. G., Caprihan, A., Qualls, C., Apfeldorf, W. J., Lauriello, J., & Posse, S. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.08.024 · Cited by 94 · see citing works
Synapse structure: glutamate receptors connected by the shanks
Ehlers, M. D. (1999) · Current Biology · doi:10.1016/s0960-9822(00)80043-3 · Cited by 93 · see citing works
Hefti, K., Holst, S. C., Sóvágó, J., Bachmann, V., Buck, A., Ametamey, S. M., Scheidegger, M., Berthold, T., Gomez‐Mancilla, B., Seifritz, E., et al. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.07.030 · Cited by 93 · see citing works
Striatal glutamate and the conversion to psychosis: a prospective 1H-MRS imaging study
de la Fuente‐Sandoval, C., León-Ortíz, P., Azcárraga, M., Favila, R., Stephano, S., & Graff‐Guerrero, A. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712000314 · Cited by 88 · see citing works
Kelly, D. L., Conley, R. R., & Carpenter, W. T. (2005) · Drugs · doi:10.2165/00003495-200565080-00006 · Cited by 87 · see citing works
Metabotropic Glutamate Receptors: Potential Drug Targets for the Treatment of Schizophrenia
Chavez-Noriega, L. E., Schaffhauser, H., & Campbell, U. C. (2002) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1568007023339337 · Cited by 85 · see citing works
Regional Decoupling of N-acetyl-aspartate and Glutamate in Schizophrenia
Kraguljac, N. V., Reid, M. A., White, D. M., den Hollander, J., & Lahti, A. C. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.126 · Cited by 84 · see citing works
Koroś, E., Rosenbrock, H., Birk, G., Weiss, C., & Sams‐Dodd, F. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301133 · Cited by 82 · see citing works
Glutathione depletion in the brain disrupts short-term spatial memory in the Y-maze in rats and mice
Dean, O. M., Bush, A. I., Berk, M., Copolov, D., & van den Buuse, M. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.11.017 · Cited by 81 · see citing works
Choe, B., Suh, T. S., Shinn, K.-S., Lee, C., Lee, C., & Paik, I. (1996) · Investigative Radiology · doi:10.1097/00004424-199606000-00006 · Cited by 79 · see citing works
Bartha, R., Al-Semaan, Y. M., Williamson, P., Drost, D. J., MALLA, A. K., Carr, T. J., Densmore, M., Canaran, G., & Neufeld, R. W. J. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00007-4 · Cited by 77 · see citing works
Yoo, S. Y., Yeon, S., Choi, C., Kang, D.-H., Lee, J., Shin, N. Y., Jung, W. H., Choi, J., Jang, D., & Kwon, J. S. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.03.036 · Cited by 76 · see citing works
Szulc, A., Galińska-Skok, B., Tarasów, E., Dzienis, W., Kubas, B., Konarzewska, B., Walecki, J. M., Alathiaki, A. S., & Czernikiewicz, A. (2005) · Pharmacopsychiatry · doi:10.1055/s-2005-873156 · Cited by 72 · see citing works
Neurochemical and structural correlates of executive dysfunction in schizophrenia
Rüsch, N., van Elst, L. T., Valerius, G., Büchert, M., Thiel, T., Ebert, D., Hennig, J., & Olbrich, H. M. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2007.05.024 · Cited by 72 · see citing works
DeLorenzo, C., Kumar, J. S. D., Mann, J. J., & Parsey, R. V. (2011) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.105 · Cited by 72 · see citing works
Sullivan, J. M., Lim, K., Labaree, D. C., Lin, S.-F., McCarthy, T. J., Seibyl, J. P., Tamagnan, G. D., Huang, Y. H., Carson, R. E., Ding, Y., et al. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.195 · Cited by 72 · see citing works
Block, W., Bayer, T. A., Tepest, R., Träber, F., Rietschel, M., Müller, D. J., Schulze, T. G., Honer, W. G., Maier, W., Schild, H. H., et al. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01264-7 · Cited by 71 · see citing works
Ohrmann, P., Kugel, H., Bauer, J., Siegmund, A., Kölkebeck, K., Suslow, T., Wiedl, K. H., Rothermundt, M., Arolt, V., & Pedersen, A. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.08.005 · Cited by 70 · see citing works
Effect of antipsychotic treatment on the prepulse inhibition deficit of mGluR5 knockout mice
Brody, S. A., Conquet, F., & Geyer, M. A. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1635-3 · Cited by 69 · see citing works
Ketamine does not decrease striatal dopamine D 2 receptor binding in man
Aalto, S., Hirvonen, J., Kajander, J., Scheinin, H., Någren, K., Vilkman, H., Gustafsson, L. L., Syvälahti, E. K. G., & Hietala, J. A. (2002) · Psychopharmacology · doi:10.1007/s00213-002-1236-6 · Cited by 69 · see citing works
Miyake, N., Skinbjerg, M., Easwaramoorthy, B., Kumar, D. J. S., Girgis, R. R., Xu, X., Slifstein, M., & Abi‐Dargham, A. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.12.023 · Cited by 67 · see citing works
Self-citationTaylor, M. J., Tiangga, E. R., Mhuircheartaigh, R. N., & Cowen, P. J. (2012) · Journal of Psychopharmacology · doi:10.1177/0269881111405359 · Cited by 66 · see citing works
Hutcheson, N. L., Reid, M. A., White, D. M., Kraguljac, N. V., Avsar, K. B., Bolding, M., Knowlton, R. C., den Hollander, J. A., & Lahti, A. C. (2012) · Schizophrenia Research · doi:10.1016/j.schres.2012.06.039 · Cited by 65 · see citing works
Preliminary study of frontal lobe 1H MR spectroscopy in childhood‐onset schizophrenia
Thomas, M. A., Ke, Y., Levitt, J. G., Caplan, R., Curran, J. G., Asarnow, R. F., & McCracken, J. T. (1998) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.1880080413 · Cited by 61 · see citing works
Wood, S. J., Yücel, M., Wellard, R. M., Harrison, B. J., Clarke, K., Fornito, A., Velakoulis, D., & Pantelis, C. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2007.05.008 · Cited by 60 · see citing works
DeLorenzo, C., Milak, M. S., Brennan, K. G., Kumar, J. S. D., Mann, J. J., & Parsey, R. V. (2011) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-010-1723-7 · Cited by 60 · see citing works
Keshavan, M. S., Dick, R. M., Diwadkar, V. A., Montrose, D. M., Prasad, K. M. R., & Stanley, J. A. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.08.012 · Cited by 59 · see citing works
Valli, I., Stone, J. M., Mechelli, A., Bhattacharyya, S., Raffin, M., Allen, P., Fusar‐Poli, P., Lythgoe, D. J., Tuura, R., Seal, M. L., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.08.033 · Cited by 59 · see citing works
Yoshimura, R., Gotō, N., Kakeda, S., Nishimura, J., Moriya, J., Hayashi, K., Hori, H., Ikenouchi, A., Umen-Nakano, W., Katsuki, A., et al. (2012) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s25582 · Cited by 58 · see citing works
Bressan, R. A., Erlandsson, K., Stone, J. M., Mulligan, R. S., Krystal, J. H., Ell, P. J., & Pilowsky, L. S. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.03.016 · Cited by 57 · see citing works
Behavioral and biochemical effects of glutathione depletion in the rat brain
Cruz-Aguado, R., Almaguer‐Melian, W., Díaz, C. M., et al. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00484-1 · Cited by 53 · see citing works
Proton Magnetic Resonance Spectroscopy in 22q11 Deletion Syndrome
Alves, F. D. S., Boot, E., Schmitz, N., Nederveen, A. J., Vorstman, J. A. S., Lavini, C., Pouwels, P. J. W., de Haan, L., LINSZEN, D. H., & van Amelsvoort, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021685 · Cited by 51 · see citing works
Szulc, A., Galińska-Skok, B., Tarasów, E., Waszkiewicz, N., Konarzewska, B., Popławska, R., Bibulowicz, D., Simonienko, K., & Walecki, J. M. (2011) · Pharmacopsychiatry · doi:10.1055/s-0031-1279739 · Cited by 51 · see citing works
Translational characterization of [11C]GSK931145, a PET ligand for the glycine transporter type 1
Gunn, R. N., Murthy, V., Catafau, A. M., et al. (2011) · Synapse · doi:10.1002/syn.20966 · Cited by 50 · see citing works
Galińska-Skok, B., Szulc, A., Tarasów, E., Kubas, B., Dzienis, W., Czernikiewicz, A., & Walecki, J. M. (2009) · PubMed · Cited by 50 · see citing works
Modulation of Striatal Dopamine Release by Glycine Transport Inhibitors
Javitt, D., Hashim, A., & Sershen, H. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300589 · Cited by 48 · see citing works
Self-citationMartin‐Facklam, M., Pizzagalli, F., Zhou, Y., et al. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.212 · Cited by 48 · see citing works
Trabesinger, A. H., & Boesiger, P. (2001) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1094 · Cited by 42 · see citing works
Elmenhorst, D., Aliaga, A., Bauer, A., & Rosa‐Neto, P. (2012) · Synapse · doi:10.1002/syn.21542 · Cited by 35 · see citing works
Hamill, T. G., Eng, W., Jennings, A. S. R., Lewis, R. T., Thomas, S., Wood, S., Street, L. J., Wisnoski, D. D., Wolkenberg, S. E., Lindsley, C. W., et al. (2010) · Synapse · doi:10.1002/syn.20842 · Cited by 34 · see citing works
Proton magnetic resonance spectroscopy and thought disorder in childhood schizophrenia
Seese, R. R., O’Neill, J., Hudkins, M. R., Siddarth, P., Levitt, J. G., Tseng, B., Wu, K. N., & Caplan, R. (2011) · Schizophrenia Research · doi:10.1016/j.schres.2011.07.011 · Cited by 30 · see citing works
Glutamatergic changes in the cerebral white matter associated with schizophrenic exacerbation
Ota, M., Ishikawa, M., Sato, N., Hori, H., Sasayama, D., Hattori, K., Teraishi, T., Nakata, Y., & Kunugi, H. (2012) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2012.01853.x · Cited by 29 · see citing works
New double quantum coherence filter for localized detection of glutathione in vivo
Zhao, T., Heberlein, K., Jonas, C. R., et al. (2006) · Magnetic Resonance in Medicine · doi:10.1002/mrm.20788 · Cited by 29 · see citing works
Wong, D. F., Ostrowitzki, S., Zhou, Y., et al. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.11.052 · Cited by 26 · see citing works
Cell-type specificity of mGluR activation in striatal neuronal subtypes
Pisani, A., Bernardi, G., Bonsi, P., et al. (2000) · Amino Acids · doi:10.1007/s007260070040 · Cited by 25 · see citing works
Théberge, J., Al-Semaan, Y. M., Jensen, J. E., et al. (2004) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2004.08.001 · Cited by 22 · see citing works
Evaluation of NMDA Receptors in Vivo in Schizophrenic Patients with [123I]CNS 1261 and SPET
Bressan, R. A., Erlandsson, K., Mulligan, R. S., et al. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1300.027 · Cited by 16 · see citing works
Bullich, S., Slifstein, M., Passchier, J., et al. (2010) · Molecular Imaging and Biology · doi:10.1007/s11307-010-0398-6 · Cited by 16 · see citing works
Self-citationHuang, H.-L., Yeh, C., Chang, K., et al. (2012) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2012.04.091 · Cited by 10 · see citing works
Çağlar, M., I, I. I., AL, H., et al. (2001) · Nuclear Medicine Communications · doi:10.1097/00006231-200101000-00005 · Cited by 5 · see citing works
Zheng, M., Holden, D., Hamill, T. G., et al. (2013) · Journal of Nuclear Medicine · Cited by 4 · see citing works
Munowitz, M. G. (2007) · Encyclopedia of Magnetic Resonance · doi:10.1002/9780470034590.emrstm0131 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
An integrative perspective on the role of dopamine in schizophrenia
Maia, T. V., & Frank, M. J. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.05.021 · Cited by 293 · see citing works
Steullet, P., Cabungcal, J. H., Monin, A., Dwir, D., O'Donnell, P., Cuenod, M., & Do, K. Q. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2014.06.021 · Cited by 262 · see citing works
Altered Cortical Ensembles in Mouse Models of Schizophrenia
Hamm, J. P., Peterka, D. S., Gogos, J. A., & Yuste, R. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.019 · Cited by 175 · see citing works
Are hallucinations due to an imbalance between excitatory and inhibitory influences on the brain?
Jardri, R., Hugdahl, K., Hughes, M., Brunelin, J., Waters, F., Alderson-Day, B., Smailes, D., Sterzer, P., Corlett, P. R., Leptourgos, P., et al. (2016) · Schizophrenia Bulletin · doi:10.1093/schbul/sbw075 · Cited by 157 · see citing works
Development of targeted alpha particle therapy for solid tumors.
Tafreshi, N. K., Doligalski, M. L., Tichacek, C. J., Pandya, D. N., Budzevich, M. M., El-Haddad, G., Khushalani, N. I., Moros, E. G., McLaughlin, M. L., Wadas, T. J., et al. (2019) · Molecules · doi:10.3390/molecules24234314 · Cited by 157 · see citing works
Millan, M. J., Goodwin, G. M., Meyer-Lindenberg, A., & Ove Ögren, S. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.01.016 · Cited by 132 · see citing works
Javitt, D. C., Carter, C. S., Krystal, J. H., Kantrowitz, J. T., Girgis, R. R., Kegeles, L. S., Ragland, J. D., Maddock, R. J., Lesh, T. A., Tanase, C., et al. (2018) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.3572 · Cited by 100 · see citing works
Self-citationGlutamate as a mediating transmitter for auditory hallucinations in schizophrenia: A 1H MRS study
Hugdahl, K., Craven, A. R., Nygård, M., Løberg, E.-M., Berle, J. Ø., Johnsen, E., Kroken, R., Specht, K., Andreassen, O. A., & Ersland, L. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2014.11.015 · Cited by 64 · see citing works
Evolving toward a human-cell based and multiscale approach to drug discovery for CNS disorders
Schadt, E. E., Buchanan, S., Brennand, K. J., & Merchant, K. M. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00252 · Cited by 39 · see citing works
Kosten, L., Verhaeghe, J., wyffels, L., Stroobants, S., & Staelens, S. (2018) · Molecular Imaging · doi:10.1177/1536012118788636 · Cited by 17 · see citing works
- Authors
- Poels, E. M. P., Kegeles, L. S., Kantrowitz, J. T., Slifstein, M., Javitt, D. C., Lieberman, J. A., Abi-Dargham, A., & Girgis, R. R.
- Affiliations
- New York State Psychiatric Institute (US)
- Corresponding author
- Girgis, R R
- Venue
- Molecular Psychiatry
- Published
- 2013-10-29
- Volume
- 19
- Issue
- 1
- Pages
- 20-29
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W1997446269
- Cited by
- 205
- References
- 142
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 5 · 2023: 5 · 2022: 8 · 2021: 14 · 2020: 21 · 2019: 18 · 2018: 21 · 2017: 23 · 2016: 21 · 2015: 35 · 2014: 22
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- F. Hoffmann-La Roche
- National Institutes of Health (5p50mh066171-05)
- National Institute of Mental Health (P50MH066171-01A1)
- National Center for Research Resources (KL2RR024157)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, glutamate, NMDA receptor hypofunction, glutamate imaging, 1H NMR, glutathione, glycine
- MeSH terms
- Animals, Humans, Schizophrenia, Glutamic Acid, Drug Discovery, Neuroimaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review