Increased cortical kynurenate content in schizophrenia
Abstract
Background Metabolites of the kynurenine pathway of tryptophan degradation may play a role in the pathogenesis of several human brain diseases. One of the key metabolites in this pathway, kynurenine, is either transaminated to form the glutamate receptor antagonist, kynurenate, or hydroxylated to 3-hydroxykynurenine, which in turn is further degraded to the excitotoxic N-methyl-D-aspartate receptor agonist quinolinate. Because a hypoglutamatergic tone may be involved in the pathophysiology of schizophrenia, it is conceivable that alterations in kynurenine pathway metabolism may play a role in the disease.Methods The tissue levels of kynurenine, kynurenate, and 3-hydroxykynurenine were measured in brain tissue specimens obtained from the Maryland Brain Collection. All three metabolites were determined in the same samples from three cortical brain regions (Brodmann areas 9, 10, and 19), obtained from 30 schizophrenic and 31 matched control subjects.Results Kynurenate levels were significantly increased in schizophrenic cases in Brodmann area 9 (2.9 +/- 2.2 vs. 1.9 +/- 1.3 pmol/mg protein, p <.05), but not in Brodmann areas 10 and 19. Kynurenine levels were elevated in schizophrenic cases in Brodmann areas 9 (35.2 +/- 28.0 vs. 22.4 +/- 14.3 pmol/mg protein; p <.05) and 19 (40.3 +/- 23.4 vs. 30.9 +/- 10.8; p <.05). No significant differences in 3-hydroxykynurenine content were observed between the two groups. In both groups, significant (p <.05) correlations were found in all three brain areas between kynurenine and kynurenate, but not between kynurenine and 3-hydroxykynurenine (p >.05). In rats, chronic (6-months) treatment with haloperidol did not cause an increase in kynurenate levels in the frontal cortex, indicating that the elevation observed in schizophrenia is not due to antipsychotic medication.Conclusions The data demonstrate an impairment of brain kynurenine pathway metabolism in schizophrenia, resulting in elevated kynurenate levels and suggesting a possible concomitant reduction in glutamate receptor function.
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?
Post-mortem studies of schizophrenia brains revealed lower GRIN1 expression, increases in kynurenate, and reductions in D-serine and D-serine racemase.
“Post-mortem studies of the brain of patients with schizophrenia have revealed lower levels of expression of the obligate NMDAR subunit GRIN1 (glutamate receptor ionotropic, NMDA 1), increases in the expression of the endogenous NMDAR antagonist kynurenate, and a reduction in levels of the NMDAR co-agonist D-serine and the enzyme that catalyses its production, D-serine racemase 10,[16][17][18] .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [16]
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
Krystal, J. H. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950030035004 · Cited by 3,330 · 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
Anis, N. A., Berry, S. C., Burton, N. R., & Lodge, D. (1983) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1983.tb11031.x · Cited by 1,399 · see citing works
Quinolinic Acid: An Endogenous Metabolite That Produces Axon-Sparing Lesions in Rat Brain
Schwarcz, R. M., Whetsell, W. O., & Mangano, R. M. (1983) · Science · doi:10.1126/science.6849138 · Cited by 1,269 · see citing works
Self-citationSubanesthetic Doses of Ketamine Stimulate Psychosis in Schizophrenia
Lahti, A. C., Koffel, B., LaPorte, D. J., & Tamminga, C. A. (1995) · Neuropsychopharmacology · doi:10.1016/0893-133x(94)00131-i · Cited by 921 · see citing works
Self-citationHypofrontality in Neuroleptic-Naive Patients and in Patients With Chronic Schizophrenia
Andreasen, N. C. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820120031006 · Cited by 883 · see citing works
Perkins, M. N., & Stone, T. W. (1982) · Brain Research · doi:10.1016/0006-8993(82)91048-4 · Cited by 849 · see citing works
Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia
Kim, J. S., Kornhuber, H. H., Schmid‐Burgk, W., & Holzmüller, B. (1980) · Neuroscience Letters · doi:10.1016/0304-3940(80)90178-0 · Cited by 694 · see citing works
Schizophrenia, sensory gating, and nicotinic receptors
Adler, L. E., Olincy, A., Waldo, M., Harris, J. G., Griffith, J., Stevens, K., Flach, K., Nagamoto, H., Bickford, P., Leonard, S., et al. (1998) · Schizophrenia Bulletin · doi:10.1093/oxfordjournals.schbul.a033320 · Cited by 690 · see citing works
D-Alanine Added to Antipsychotics for the Treatment of Schizophrenia
Tsai, G. E., Yang, P., Chang, Y., & Chong, M. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.06.032 · Cited by 676 · see citing works
D-serine added to antipsychotics for the treatment of schizophrenia
Tsai, G. E., Yang, P., Chung, L.-C., LANGE, N. D., & Coyle, J. T. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00279-0 · Cited by 572 · see citing works
Clinical Experience With Excitatory Amino Acid Antagonist Drugs
Muir, K. W., & Lees, K. R. (1995) · Stroke · doi:10.1161/01.str.26.3.503 · Cited by 503 · see citing works
Efficacy of High-Dose Glycine in the Treatment of Enduring Negative Symptoms of Schizophrenia
Heresco‐Levy, U., Javitt, D. C., Ermilov, M., Mordel, C., Silipo, G. S., & Lichtenstein, M. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.1.29 · Cited by 487 · see citing works
Abnormal Excitatory Neurotransmitter Metabolism in Schizophrenic Brains
Tsai, G. E. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950220039008 · Cited by 455 · see citing works
Akbarian, S., Sucher, N. J., Bradley, D., Tafazzoli, A., Trinh, D., Hetrick, W. P., Potkin, S. G., Sandman, C., Bunney, W. E., & Jones, E. G. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-01-00019.1996 · Cited by 440 · see citing works
Schizophrenia and Glutamatergic Transmission
Tamminga, C. A. (1998) · Critical Reviews in Neurobiology · doi:10.1615/critrevneurobiol.v12.i1-2.20 · Cited by 385 · see citing works
Self-citationGao, X.-M., Sakai, K., Roberts, R. C., Conley, R. R., Dean, B., & Tamminga, C. A. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.7.1141 · Cited by 371 · see citing works
Self-citationTryptophan metabolism and brain function: focus on kynurenine and other indole metabolites
Moroni, F. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(99)00196-x · Cited by 347 · see citing works
Schizophrenia: A Subcortical Neurotransmitter Imbalance Syndrome?
Carlsson, M. L., & Carlsson, A. C. (1990) · Schizophrenia Bulletin · doi:10.1093/schbul/16.3.425 · Cited by 341 · see citing works
Frontostriatal Disorder of Cerebral Metabolism in Never-Medicated Schizophrenics
Buchsbaum, M. S. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820120023005 · Cited by 324 · see citing works
Okuda, S., Nishiyama, N., Saitō, H., & Katsuki, H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.22.12553 · Cited by 302 · see citing works
Presence of Kynurenic Acid in the Mammalian Brain
Moroni, F., Russi, P., Lombardi, G., Beni, M. H. H., & Carla�, V. (1988) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1988.tb04852.x · Cited by 279 · see citing works
Identification and quantification of kynurenic acid in human brain tissue
Turski, W. A., Nakamura, M., Todd, W. P., Carpenter, B. K., Whetsell, W. O., & Schwarcz, R. M. (1988) · Brain Research · doi:10.1016/0006-8993(88)90815-3 · Cited by 220 · see citing works
Self-citationRat Brain Slices Produce and Liberate Kynurenic Acid upon Exposure to l ‐Kynurenine
Turski, W. A., Gramsbergen, J. B., Traitler, H., et al. (1989) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1989.tb09218.x · Cited by 218 · 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
Parsons, C., Danysz, W., Quack, G. ̈., Hartmann, S., Lorenz, B., Wollenburg, C., Baran, L., Przegaliński, E., Kostowski, W., Krza̧ścik, P., et al. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37160-5 · Cited by 207 · see citing works
The excitatory amino acid antagonist d-CPP-ene (SDZ EAA-494) in patients with epilepsy
Sveinbjörnsdóttir, S., Sander, J. W. A. S., Upton, D., Thompson, P. J., Patsalos, P. N., Hirt, D., Emre, M., Lowe, D., & Duncan, J. S. (1993) · Epilepsy Research · doi:10.1016/0920-1211(93)90031-2 · Cited by 200 · see citing works
Changes in mitochondrial membrane potential during oxidative stress-induced apoptosis in PC12 cells
Satoh, T., Enokido, Y., Aoshima, H., Uchiyama, Y., & Hatanaka, H. (1997) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19971101)50:3 · Cited by 196 · see citing works
Two kynurenine aminotransferases in human brain
Okuno, E., Nakamura, M., & Schwarcz, R. M. (1991) · Brain Research · doi:10.1016/0006-8993(91)91583-m · Cited by 166 · see citing works
Self-citationCytotoxicity of 3-hydroxykynurenine in a neuronal hybrid cell line
Eastman, C. L., & Guilarte, T. R. (1989) · Brain Research · doi:10.1016/0006-8993(89)90216-3 · Cited by 161 · see citing works
Heyes, M. P., Brew, B. J., Saito, K., Quearry, B. J., Price, R. W., Lee, K., Bhalla, R. B., Der, M. G., & Markey, S. P. (1992) · Journal of Neuroimmunology · doi:10.1016/0165-5728(92)90214-6 · Cited by 140 · see citing works
Miranda, A., Boegman, R. J., Beninger, R. J., & Jhamandas, K. H. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00655-0 · Cited by 139 · see citing works
Pellicciari, R., Natalini, B., Costantino, G., et al. (1994) · Journal of Medicinal Chemistry · doi:10.1021/jm00031a015 · Cited by 137 · see citing works
Neuroprotective Effects of L-Kynurenine on Hypoxia—Ischemia and NMDA Lesions in Neonatal Rats
Nozaki, K., & Beal, M. F. (1992) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1992.57 · Cited by 136 · see citing works
Breese, C. R., Freedman, R., & Leonard, S. S. (1995) · Brain Research · doi:10.1016/0006-8993(94)01384-t · Cited by 134 · see citing works
Lodge, D., Anis, N. A., & Burton, N. R. (1982) · Neuroscience Letters · doi:10.1016/0304-3940(82)90330-5 · Cited by 130 · see citing works
Swartz, K. J., Matson, W. R., MacGarvey, U. M., et al. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90309-w · Cited by 127 · see citing works
Vécsei, L., Miller, J. M., Macgarvey, U., & Beal, M. (1992) · Brain Research Bulletin · doi:10.1016/0361-9230(92)90184-y · Cited by 118 · see citing works
HOLMES, E. W. (1988) · Analytical Biochemistry · doi:10.1016/0003-2697(88)90478-2 · Cited by 113 · see citing works
Brain‐Specific Modulation of Kynurenic Acid Synthesis in the Rat
Gramsbergen, J. B., Hodgkins, P., Rassoulpour, A., Turski, W. A., Guidetti, P., & Schwarcz, R. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69010290.x · Cited by 105 · see citing works
Self-citationChiarugi, A., Carpenedo, R., Molina, M. T., Mattoli, L., Pellicciari, R., & Moroni, F. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65031176.x · Cited by 105 · see citing works
NMDA receptor mRNA correlation with antemortem cognitive impairment in schizophrenia
Humphries, C., Mortimer, A. M., Hirsch, S. R., & de Belleroche, J. (1996) · Neuroreport · doi:10.1097/00001756-199608120-00040 · Cited by 102 · see citing works
Cerebrospinal fluid levels of quinolinic acid in Huntington's disease and schizophrenia
Schwarcz, R. M., Tamminga, C. A., Kurlan, R., & Shoulson, I. (1988) · Annals of Neurology · doi:10.1002/ana.410240417 · Cited by 102 · see citing works
Self-citationThe novel antipsychotic drugs.
Meltzer, H. Y. (2002) · PubMed · Cited by 101 · see citing works
Eastwood, S. L., Burnet, P. W. J., & Harrison, P. J. (1997) · Molecular Brain Research · doi:10.1016/s0169-328x(96)00195-7 · Cited by 101 · see citing works
Ganguli, R. (1993) · Schizophrenia Research · doi:10.1016/0920-9964(93)90016-c · Cited by 97 · see citing works
Guidetti, P., Eastman, C. L., & Schwarcz, R. M. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65062621.x · Cited by 94 · see citing works
Self-citationGlutamate in schizophrenia: clinical and research implications
GOFF, D. C., & Wine, L. (1997) · Schizophrenia Research · doi:10.1016/s0920-9964(97)00079-0 · Cited by 93 · see citing works
Leiderman, E. A., Zylberman, I., Zukin, S. R., Cooper, T. B., & Javitt, D. C. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00585-4 · Cited by 90 · see citing works
Modulation of striatal quinolinate neurotoxicity by elevation of endogenous brain kynurenic acid
Harris, C. A., Miranda, A., Tanguay, J., et al. (1998) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701834 · Cited by 88 · see citing works
Joseph, M. H., Baker, H. F., Crow, T. J., Riley, G. J., & Risby, D. (1979) · Psychopharmacology · doi:10.1007/bf00431959 · Cited by 80 · see citing works
Heyes, M. P., & Quearry, B. J. (1988) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(00)83925-0 · Cited by 77 · see citing works
Kynurenic Acid in the Quinolinate‐lesioned Rat Hippocampus: Studies In Vitro and In Vivo
Wu, H., Baran, H., Ungerstedt, U., et al. (1992) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1992.tb00152.x · Cited by 70 · see citing works
Self-citationOn the disposition of intrahippocampally injected kynurenic acid in the rat
Turski, W. A., & Schwarcz, R. M. (1988) · Experimental Brain Research · doi:10.1007/bf00248748 · Cited by 63 · see citing works
Self-citationRecent Advances in Tryptophan Research
Filippini, G., Costa, C., & Bertazzo, A. (1996) · Advances in experimental medicine and biology · doi:10.1007/978-1-4613-0381-7 · Cited by 59 · see citing works
Gáal, E. M., Young, R. B., & Sherman, A. D. (1978) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1978.tb12454.x · Cited by 56 · see citing works
Pöeggeler, B., Rassoulpour, A., Guidetti, P., et al. (1998) · Developmental Neuroscience · doi:10.1159/000017309 · Cited by 54 · see citing works
Self-citationQuinolinic Acid in Neurological Disease: Opportunities for Novel Drug Discovery
Reinhard, J. F., Erickson, J. B., & Flanagan, E. M. (1994) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60173-8 · Cited by 40 · see citing works
2‐Oxoacids Regulate Kynurenic Acid Production in the Rat Brain
Hodgkins, P., Wu, H., Zielke, R. H., & Schwarcz, R. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0720643.x · Cited by 36 · see citing works
Self-citationThe Glutamate Hypothesis of Schizophrenia
Ishimaru, M. J., & Toru, M. (1997) · CNS Drugs · doi:10.2165/00023210-199707010-00006 · Cited by 34 · see citing works
Jauch, D., Sethy, V. H., Weick, B. G., et al. (1993) · Neuropharmacology · doi:10.1016/0028-3908(93)90171-x · Cited by 34 · see citing works
Gao, X., Hashimoto, T., Cooper, T. B., et al. (1997) · Journal of Neural Transmission · doi:10.1007/bf01271298 · Cited by 31 · see citing works
Issa, F., Gerhardt, G. A., Bartko, J. J., et al. (1994) · Psychiatry Research · doi:10.1016/0165-1781(94)90069-8 · Cited by 29 · see citing works
Speciale, C., Cini, M., Wu, H., et al. (1996) · Advances in experimental medicine and biology · doi:10.1007/978-1-4613-0381-7_35 · Cited by 26 · see citing works
Self-citationIs there a viral or immune dysfunction etiology to schizophrenia? Re-evaluation a decade later
DeLisi, L. E. (1996) · Schizophrenia Research · doi:10.1016/0920-9964(96)00061-8 · Cited by 25 · see citing works
Issa, F., Kirch, D. G., Gerhardt, G. A., et al. (1994) · Psychiatry Research · doi:10.1016/0165-1781(94)90070-1 · Cited by 17 · see citing works
Increased CSF and brain quinolinic acid in schizophrenia and bipolar disorder
Torrey, E. F., Yolken, R. H., Zito, M. F., et al. (1998) · Schizophrenia Research · doi:10.1016/s0920-9964(97)88530-1 · Cited by 7 · see citing works
Johnston, N. L., Shore, A., Yolken, R. H., et al. (1998) · Schizophrenia Research · doi:10.1016/s0920-9964(97)88528-3 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mammalian nicotinic acetylcholine receptors: from structure to function
Albuquerque, E. X., Pereira, E. F. R., Alkondon, M., & Rogers, S. W. (2009) · Physiological Reviews · doi:10.1152/physrev.00015.2008 · Cited by 1,724 · see citing works
Kynurenines in the mammalian brain: when physiology meets pathology
Schwarcz, R., Bruno, J. P., Muchowski, P. J., & Wu, H.-Q. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3257 · Cited by 1,530 · see citing works
Self-citationGlutamate and Schizophrenia: Beyond the Dopamine Hypothesis
Coyle, J. T. (2006) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-006-9062-8 · Cited by 917 · see citing works
Autism‐like behavioral phenotypes in BTBR T+tf/J mice
McFarlane, H. G., Kusek, G. K., Yang, M., Phoenix, J. L., Bolivar, V. J., & Crawley, J. N. (2008) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2007.00330.x · Cited by 812 · see citing works
Inflammation in schizophrenia: pathogenetic aspects and therapeutic considerations.
Müller, N. (2018) · Schizophrenia Bulletin · doi:10.1093/schbul/sby024 · Cited by 648 · 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
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
Rudzki, L., Ostrowska, L., Pawlak, D., Małus, A., Pawlak, K., Waszkiewicz, N., & Szulc, A. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.10.010 · Cited by 499 · see citing works
Kynurenines in CNS disease: regulation by inflammatory cytokines.
Campbell, B. M., Charych, E., Lee, A. W., & Möller, T. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00012 · Cited by 409 · 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
Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis
Hardingham, G. E., & Do, K. Q. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.19 · Cited by 304 · see citing works
The kynurenine pathway of tryptophan degradation as a drug target
Schwarcz, R. (2004) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2003.10.006 · Cited by 265 · see citing works
Self-citationRéus, G. Z., Jansen, K., Titus, S., Carvalho, A. F., Gabbay, V., & Quevedo, J. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.05.007 · Cited by 221 · see citing works
The NMDA receptor ‘glycine modulatory site’ in schizophrenia: d-serine, glycine, and beyond
Balu, D. T., & Coyle, J. T. (2015) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2014.12.004 · Cited by 208 · see citing works
Role of Adiposity-Driven Inflammation in Depressive Morbidity
Capuron, L., Lasselin, J., & Castanon, N. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.123 · Cited by 182 · see citing works
Glutamatergic Synaptic Dysregulation in Schizophrenia: Therapeutic Implications
Coyle, J. T., Basu, A., Benneyworth, M., Balu, D., & Konopaske, G. (2012) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-25758-2_10 · 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
Neuropsychiatric disorders related to interferon and interleukins treatment
Myint, A. M., Schwarz, M. J., Steinbusch, H. W. M., & Leonard, B. E. (2009) · Metabolic Brain Disease · doi:10.1007/s11011-008-9114-5 · Cited by 116 · see citing works
Brand, S., Moller, M., & Harvey, B. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666150307004545 · Cited by 95 · see citing works
Kynurenine pathway in psychosis: evidence of increased tryptophan degradation
Barry, S., Clarke, G., Scully, P., & Dinan, T. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881108089583 · Cited by 96 · see citing works
CSF biomarkers in suicide attempters – a principal component analysis
Lindqvist, D., Janelidze, S., Erhardt, S., Träskman‐Bendz, L., Engström, G., & Brundin, L. (2011) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2010.01655.x · Cited by 86 · see citing works
Anti-inflammatory treatment in schizophrenia
Müller, N., Myint, A.-M., Krause, D., Weidinger, E., & Schwarz, M. J. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.11.008 · Cited by 89 · see citing works
Modeling autism-relevant behavioral phenotypes in rats and mice: Do ‘autistic’ rodents exist?
Servadio, M., Vanderschuren, L. J. M. J., & Trezza, V. (2015) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000163 · Cited by 76 · see citing works
Timofeeva, O. A., & Levin, E. D. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.08.038 · Cited by 74 · see citing works
Gos, T., Myint, A.-M., Schiltz, K., Meyer-Lotz, G., Dobrowolny, H., Busse, S., Müller, U. J., Mawrin, C., Bernstein, H.-G., Bogerts, B., et al. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.05.012 · Cited by 49 · see citing works
Orhan, F., Bhat, M., Sandberg, K., Ståhl, S., Piehl, F., Karolinska Schizophrenia Project (KaSP) consortium, Svensson, C., Erhardt, S., & Schwieler, L. (2016) · Scandinavian Journal of Immunology · doi:10.1111/sji.12479 · Cited by 47 · see citing works
Zavitsanou, K., Lim, C. K., Purves-Tyson, T., Karl, T., Kassiou, M., Banister, S. D., Guillemin, G. J., & Weickert, C. S. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.05.011 · Cited by 46 · see citing works
Comorbidity of mental and physical disorders
(2014) · Key Issues in Mental Health · doi:10.1159/isbn.978-3-318-02604-7 · Cited by 37 · see citing works
Recent advances in psychoneuroimmunology: Inflammation in psychiatric disorders
Debnath, M., Doyle, K., Langan, C., McDonald, C., Leonard, B., & Cannon, D. (2011) · Translational Neuroscience · doi:10.2478/s13380-011-0019-0 · Cited by 28 · see citing works
Atlas, A., Franzen-Röhl, E., Söderlund, J., Jönsson, E. G., Samuelsson, M., Schwieler, L., Sköldenberg, B., & Engberg, G. (2013) · International Journal of Tryptophan Research · doi:10.4137/ijtr.s13256 · Cited by 25 · see citing works
Costa, A., Riça, L., van de Bilt, M., Zandonadi, F., Gattaz, W., Talib, L., & Sussulini, A. (2023) · Metabolites · doi:10.3390/metabo13050600 · Cited by 25 · see citing works
- Authors
- Schwarcz, R., Rassoulpour, A., Wu, H.-Q., Medoff, D., Tamminga, C. A., & Roberts, R. C.
- Affiliations
- University of Maryland, Baltimore (US)
- Corresponding author
- Schwarcz, Robert
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2001-10
- Volume
- 50
- Issue
- 7
- Pages
- 521-530
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2017661386
- Cited by
- 590
- References
- 69
- Citations by year
- 2026: 15 · 2025: 13 · 2024: 20 · 2023: 24 · 2022: 20 · 2021: 25 · 2020: 32 · 2019: 17 · 2018: 24 · 2017: 32 · 2016: 35 · 2015: 45 · 2014: 42 · 2013: 25 · 2012: 29
- FWCI
- 4.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01mh053494-03)
- National Institute of Mental Health (MH53494)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD16596, P01HD016596)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- schizophrenia, kynurenine pathway, kynurenic acid, 3-hydroxykynurenine, tryptophan metabolism, Brodmann area 9, glutamatergic dysfunction, NMDA receptor, quinolinic acid, haloperidol, antipsychotic effects, brain metabolites
- MeSH terms
- Adult, Aged, Aged, 80 and over, Animals, Female, Frontal Lobe, Haloperidol, Humans, Kynurenic Acid, Kynurenine, Male, Middle Aged, Occipital Lobe, Schizophrenia, Antipsychotic Agents, Rats, Sprague-Dawley, Rats
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
