4
Views
9
CrossRef citations to date
0
Altmetric
Original

Signal transmission, rather than reception, is the underlying neurochemical abnormality in schizophrenia

Pages 560-569 | Received 13 Oct 1999, Accepted 12 Jan 2000, Published online: 07 Aug 2009

References

  • Chua SE, McKenna PJ. Schizophrenia ‐ a brain disease? A critical review of structural and functional cerebral abnormality in the disorder. British Journal of Psychiatry 1995; 166: 563–582
  • Stahl S. Psychopharmacology of antipsychotics. Marin Dunitz, London 1999
  • Carlsson A, Linquist M. Effect of chlorpromazine or haloperidol on formation of 3‐methoxy‐tyramine and normetanephrine in mouse brain. Acta Pharmacologia et Toxicologia 1963; 20: 140–144
  • Meltzer HY. Biological studies in schizophrenia. Schizophrenia Bulletin 1987; 13: 77–107
  • Bird ED, Spokes EG, Barnes J, Mackay AVP, Iversen LL, Shepherd M. Increased brain dopamine and reduced glutamic acid decarboxylase and choline acetyl transferase activity in schizophrenia and related psychoses. Lancet 1977; ii: 1157–1159
  • Reynolds GP. Increased concentrations and lateral asymmetries of amygdala dopamine in schizophrenia. Nature 1983; 305: 527–529
  • Toru M, Nishikawa T, Mataga N, Tashima M. Dopamine metabolism increases in post‐mortem schizophrenic basal ganglia. Journal of Neural Transmission 1982; 54: 181–191
  • Beskow J, Gottfries CG, Roos BE, Winblad B. Determination of monoamine and monoamine metabolites in the human brain: post mortem studies in a group of suicides and in a control group. Acta Psychiatrica Scandinavica 1976; 53: 7–20
  • Bachus SE, Kleinman JE. The neuropathology of schizophrenia. Journal of Clinical Psychiatry 1996; 57(Suppl. 11)72–83
  • Reynolds GP, Reynolds LM, Riederer P, Jellinger K, Gabriel E. Dopamine receptors and schizophrenia: drug effect or illness. Lancet 1980; i: 1251
  • Kebabian JW, Calne DB. Multiple receptors for dopamine. Nature 1979; 277: 93–96
  • Sibley DR, Monsma FJ. Molecular biology of dopamine receptors. Trends in Pharmacological Sciences 1992; 13: 61–69
  • Roberts DA, Balderson D, Pickering‐Brown SM, Deakin JFW, Owen F. The abundance of mRNA for dopamine D2 receptor isoforms in brain tissue from controls and schizophrenics. Brain Research: Molecular Brain Research 1994; 25: 173–175
  • Van Tol HHM, Bunzow JR, Guan H‐C, et al. Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 1991; 350: 610–614
  • Baldessarini RJ, Frankenburg FR. Clozapine: a novel antipsychotic agent. New England Medical Journal 1991; 324: 746–754
  • Meador‐Woodruff JH, Haroutunian V, Powchik P, Davidson M, Davis KL, Watson SJ. Dopamine receptor transcript expression in striatum and prefrontal and occipital cortex ‐ focal abnormalities in orbitofrontal cortex in schizophrenia. Archives of General Psychiatry 1997; 54: 1089–1095
  • Dean B, Pavey G, Opeskin K. [3H]raclopride binding to brain tissue from subjects with schizophrenia: methodological aspects. Neuropharmacology 1997; 36: 779–786
  • Stefanis NC, Bresnick JN, Kerwin RW, Schofield WN, McAllister G. Elevation of D4 dopamine receptor mRNA in postmortem schizophrenic brain. Brain Research: Molecular Brain Research 1998; 53: 112–119
  • Mulcrone J, Kerwin RW. No difference in the expression of the D4 gene in post‐mortem frontal cortex from controls and schizophrenics. Neuroscience Letters 1996; 219: 163–166
  • Schmauss C, Haroutunian V, Davis KL, Davidson M. Selective loss of dopamine D3‐type receptor mRNA expression in parietal and motor cortices of patients with chronic schizophrenia. Proceedings of the National Academy of Sciences of the United States of America 1993; 90: 8942–8946
  • Gilbert DB, Millar J, Cooper SJ. The putative dopamine D3 agonist, 7‐OH‐DPAT, reduces dopamine release in the nucleus accumbens and electrical self‐stimulation to the ventral tegmentum. Brain Research 1995; 681: 1–7
  • Meller E, Bohmaker K, Goldstein M, Basham DA. Evidence that striatal synthesis‐inhibiting autoreceptors are dopamine D3 receptors. European Journal of Pharmacology 1993; 249: R5–R6
  • Clark D, Hjorth S, Carlsson A. Dopamine receptor agonists: mechanisms underlying autoreceptor selectivity. II: theoretical considerations. Journal of Neural Transmission 1985; 62: 171–207
  • Laruelle M, Abi‐Dargham A, van Dyck CH, et al. Single photon emission computerized tomography imaging of amphetamine‐induced dopamine release in drug‐free schizophrenic subjects. Proceedings of the National Academy of Sciences of the United States of America 1996; 93: 9235–9240
  • Breier A, Su TP, Saunders R, Carson RE, et al. Schizophrenia is associated with elevated amphetamine‐induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proceedings of the National Academy of Sciences of the United States of America 1997; 94: 2569–2574
  • Huttunen M. The evolution of the serotonin‐dopamine antagonist concept. Journal of Clinical Psychopharmacology 1995; 15(Suppl. 1)4S–10S
  • Bennett JP, Enna SJ, Bylund DB, Gillin JC, Wyatt RJ, Snyder SH. Neurotransmitter receptors in frontal cortex of schizophrenics. Archives of General Psychiatry 1979; 36: 927–934
  • Whitaker PM, Crow TJ, Ferrier IN. Tritiated LSD binding in frontal cortex in schizophrenia. Archives of General Psychiatry 1981; 38: 278–280
  • Mita T, Hanada S, Nishino N, et al. Decreased serotonin S2 and increased dopamine D2 receptors in chronic schizophrenics. Biological Psychiatry 1986; 21: 1407–1414
  • Gurevich EV, Joyce JN. Alterations in the cortical serotonergic system in schizophrenia: a postmortem study. Biological Psychiatry 1997; 42: 529–545
  • Dean B, Hayes W, Hill C, Copolov D. Decreased serotonin 2A receptors in Brodmann's area 9 from schizophrenic subjects. A pathological or pharmacological phenomenon?. Molecular and Chemical Neuropathology 1998; 34: 133–145
  • Burnet PW, Eastwood SL, Harrison PJ. 5‐HT1A and 5‐HT2A receptor mRNA and binding site densities are differentially altered in schizophrenia. Neuropsychopharmacology 1996; 15: 442–455
  • Lewis R, Kapur S, Jones C, et al. Serotonin 5‐HT2 receptors in schizophrenia: a PET study using [18F]setoperone in neuroleptic‐naive patients and normal subjects. American Journal of Psychiatry 1999; 156: 72–78
  • Trichard C, Paillere‐Martinot ML, Attar‐Levy D, Blin J, Feline A, Martinot JL. No serotonin 5‐HT2A receptor density abnormality in the cortex of schizophrenic patients studied with PET. Schizophrenia Research 1998; 31: 13–17
  • Hashimoto T, Nishino N, Nakai H, Tanaka C. Increase in serotonin 5‐HT1A receptors in prefrontal and temporal cortices of brains from patients with chronic schizophrenia. Life Sciences 1991; 48: 355–363
  • Laruelle M, Abi‐Dargham A, Casanova MF, Toti R, Weinberger DR, Kleinman JE. Selective abnormalities of prefrontal serotonergic receptors in schizophrenia: a postmortem study. Archives of General Psychiatry 1993; 50: 810–818
  • Sumiyoshi T, Stockmeier CA, Overholser JC, Dilley GE, Meltzer HY. Serotonin 1A receptors are increased in post‐mortem prefrontal cortex in schizophrenia. Brain Research 1996; 708: 209–214
  • Simpson MDC, Lubman DI, Slater P, Deakin JFW. Autoradiography with [3H]8‐OH‐DPAT reveals increases in 5‐HT1A receptors in ventral prefrontal cortex in schizophrenia. Biological Psychiatry 1996; 39: 919–928
  • Joyce JN, Shane A, Lexow N, Winokur A, Casanova MF, Kleinman JE. Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics. Neuropsychopharmacology 1993; 8: 315–336
  • Dean B, Tomaskovic‐Crook E, Opeskin K, Keks N, Copolov D. No change in the density of the serotonin 1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex from subjects with schizophrenia. Neurochemistry International 1999; 34: 109–115
  • Hashimoto T, Kitamura N, Kajimoto Y, et al. Differential changes in serotonin 5‐HT1A and 5‐HT2 receptor binding in patients with chronic schizophrenia. Psychopharmacology 1993; 112: S35–S39
  • Dean B, Opeskin K, Pavey G, et al. [3H]paroxetine binding is altered in the hippocampus but not the frontal cortex or caudate nucleus from subjects with schizophrenia. Journal of Neurochemistry 1995; 64: 1197–1202
  • Naylor L, Dean B, Opeskin K, et al. Changes in the serotonin transporter in the hippocampus of subjects with schizophrenia identified using [3H]paroxetine. Journal of Neural Transmission 1996; 103: 749–757
  • Naylor L, Dean B, Pereira A, Mackinnon A, Kouzmenko A, Copolov D. No association between the serotonin transporter‐linked promoter region polymorphism and either schizophrenia or density of the serotonin transporter in human hippocampus. Molecular Medicine 1998; 4: 671–674
  • Deutsch SI, Mastropaolo J, Schwartz BL, Rosse RB, Morihisa JM. A ‘glutamate hypothesis’ of schizophrenia. Clinical Neuropharmacology 1989; 12: 1–13
  • Javitt DC. Negative symptoms and the PCP (phencyclidine) model of schizophrenia. Hillside Journal of Clinical Psychiatry 1987; 9: 12–35
  • Simpson MDC, Slater P, Royston MC, Deakin JFW. Alterations in phencyclidine and sigma binding sites in schizophrenic brain. Schizophrenia Research 1992; 6: 41–48
  • Dean B, Scarr E, Bradbury R, Copolov D. Decreased hippocampal (CA3) NMDA receptors in schizophrenia. Synapse 1999; 32: 67–69
  • Aparicio‐Legarza MI, Davis B, Hutson PH, Reynolds GP. Increased density of glutamate/N‐methyl‐D‐aspartate receptors in putamen from schizophrenic patients. Neuroscience Letters 1998; 241: 143–146
  • Kornhuber J, Mack‐Burkhardt F, Riederer P, et al. [3H]MK‐801 binding sites in postmortem brain regions of schizophrenic patients. Journal of Neural Transmission 1989; 77: 231–236
  • Noga JT, Hyde TM, Herman MM, et al. Glutamate receptors in the postmortem striatum of schizophrenic, suicide, and control brains. Synapse 1997; 27: 168–176
  • Grimwood S, Slater P, Deakin JF, Hutson PH. NR2B‐containing NMDA receptors are up‐regulated in temporal cortex in schizophrenia. Neuroreport 1999; 10: 461–465
  • Collingridge GL, Lester RAJ. Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacological Reviews 1989; 40: 145–210
  • Nishikawa T, Takashima M, Toru M. Increased [3H]kainic acid binding in the prefrontal cortex in schizophrenia. Neuroscience Letters 1983; 40: 245–250
  • Deakin JFW, Slater P, Simpson MDC, et al. Frontal cortical and left temporal glutamatergic dysfunction in schizophrenia. Journal of Neurochemistry 1989; 52: 1781–1786
  • Toru M, Watanabe S, Shibuya H, et al. Neurotransmitter, receptors and neuropeptides in post‐mortem brains of chronic schizophrenic patients. Acta Psychiatrica Scandinavica 1988; 78: 121–137
  • Kerwin RW, Patel S, Meldrum B. Quantitative autoradiographic analysis of glutamate binding sites in the hippocampal formation in normal and schizophrenic brain post mortem. Neuroscience 1990; 39: 25–32
  • Kurumaji A, Ishimaru M, Toru M. α‐[3H]amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid binding to human cerebral cortical membranes: minimal changes in postmortem brains of chronic schizophrenics. Journal of Neurochemistry 1992; 59: 829–837
  • Seeburg PH. The TINS/TiPS lecture: The molecular biology of mammalian glutamate receptor channels. Trends in Pharmacological Sciences 1993; 16: 359–365
  • Humphries C, Mortimer A, Hirsch S, De Belleroche J. NMDA receptor mRNA correlation with antemortem cognitive impairment in schizophrenia. Neuroreport 1996; 7: 2051–2055
  • Sokolov BP. Expression of NMDAR1, GluR1, GluR7, and KA1 glutamate receptor mRNAs is decreased in frontal cortex of ‘neuroleptic‐free’ schizophrenics: evidence on reversible up‐regulation by typical neuroleptics. Journal of Neurochemistry 1998; 71: 2454–2464
  • Akbarian S, Sucher NJ, Bradley D, et al. Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics. Journal of Neuroscience 1996; 16: 19–30
  • Harrison PJ, McLaughlin D, Kerwin RW. Decreased hippocampal expression of a glutamate receptor gene in schizophrenia. Lancet 1991; 337: 450–452
  • Porter RHP, Eastwood SL, Harrison PJ. Distribution of kainate receptor subunit mRNAs in human hippocampus, neocortex and cerebellum, and bilateral reduction of hippocampal GluR6 and KA2 transcripts in schizophrenia. Brain Research 1997; 751: 217–231
  • Eastwood SL, Burnet PW, Harrison PJ. GluR2 glutamate receptor subunit flip and flop isoforms are decreased in the hippocampal formation in schizophrenia: a reverse transcriptase‐polymerase chain reaction (RT‐PCR) study. Brain Research: Molecular Brain Research 1997; 44: 92–98
  • Eastwood SL, Kerwin RW, Harrison PJ. Immunoautoradiographic evidence for a loss of alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate‐preferring non‐N‐methyl‐D‐aspartate glutamate receptors within the medial temporal lobe in schizophrenia. Biological Psychiatry 1997; 41: 636–643
  • Bartha R, Williamson PC, Drost DJ, et al. Measurement of glutamate and glutamine in the medial prefrontal cortex of never‐treated schizophrenic patients and healthy controls by proton magnetic resonance spectroscopy. Archives of General Psychiatry 1997; 54: 959–965
  • Lahti AC, Holcomb HH, Medoff DR, Tamminga CA. Ketamine activates psychosis and alters limbic blood flow in schizophrenia. Neuroreport 1995; 6: 869–872
  • Simpson MDC, Slater P, Royston MC, Deakin JFW. Regionally selective deficits in uptake sites for glutamate and gamma‐aminobutyric acid in the basal ganglia of schizophrenics. Psychiatry Research 1992; 42: 273–282
  • Aparicio‐Legarza MI, Cutts AJ, Davis B, Reynolds GP. Deficits of [3H]D‐aspartate binding to glutamate uptake sites in striatal and accumbens tissue in patients with schizophrenia. Neuroscience Letters 1997; 232: 13–16
  • van Kammen DP. γ‐Aminobutyric acid (GABA) and the dopamine hypothesis of schizophrenia. American Journal of Psychiatry 1977; 134: 138–143
  • Perry TL, Buchanan J, Kish SJ, Hansen S. γ‐aminobutyric‐acid deficiency in brain of schizophrenic patients. Lancet 1979; i: 237–239
  • Mhatre MC, Ticku MK. Chronic GABA treatment downregulates the GABAA receptor alpha 2 and alpha 3 subunit mRNAS as well as polypeptide expression in primary cultured cerebral cortical neurons. Brain Research Molecular Brain Research 1994; 24: 159–165
  • Benes FM, Vincent SL, Alsterberg G, Bird ED, SanGiovanni JP. Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenia. Journal of Neuroscience 1992; 12: 924–929
  • Benes FM, Vincent SL, Marie A, Khan Y. Up‐regulation of GABAA receptor binding on neurons of the prefrontal cortex in schizophrenic subjects. Neuroscience 1996; 75: 1021–1031
  • Dean B, Hussain T, Hayes W, et al. Changes in serotonin2A and GABA (A) receptors in schizophrenia: studies on the human dorsolateral prefrontal cortex. Journal of Neurochemistry 1999; 72: 1593–1599
  • Benes FM, Khan Y, Vincent SL, Wickramasinghe R. Differences in the subregional and cellular distribution of GABAA receptor binding in the hippocampal formation of schizophrenic brain. Synapse 1996; 22: 338–349
  • Kiuchi Y, Kobayashi T, Takeuchi J, Shimizu H, Ogata H, Toru M. Benzodiazepine receptors increase in post‐mortem brain of chronic schizophrenics. European Archives of Psychiatry and Neurological Science 1989; 239: 71–78
  • Reynolds GP, Stroud D. Hippocampal benzodiazepine receptors in schizophrenia. Journal of Neural Transmission (General Section) 1993; 93: 151–155
  • Pandey GN, Conley RR, Pandey SC, et al. Benzodiazepine receptors in the post‐mortem brain of suicide victims and schizophrenic subjects. Psychiatry Research 1997; 71: 137–149
  • Squires RF, Lajtha A, Saederup E, Palkovits M. Reduced [3H]flunitrazepam binding in cingulate cortex and hippocampus of postmortem schizophrenic brains: is selective glutamatergic neurons associated with major psychosis?. Neurochemical Research 1993; 18: 219–223
  • Akbarian S, Huntsman MM, Kim JJ, et al. GABAA receptor subunit gene expression in human prefrontal cortex. Comparison of schizophrenics and controls. Cerebral Cortex 1995; 5: 550–560
  • Huntsman MM, Tran BV, Potkin SG, Bunney WE, Jr, Jones EG. Altered ratios of alternatively spliced long and short gamma2 subunit mRNAs of the gamma‐amino butyrate type A receptor in prefrontal cortex of schizophrenics. Proceedings of the National Academy of Sciences of the United States of America 1998; 95: 15066–15071
  • Busatto GF, Pilowsky LS, Costa DC, et al. Correlation between reduced in vivo benzodiazepine receptor binding and severity of psychotic symptoms in schizophrenia. American Journal of Psychiatry 1997; 154: 56–63
  • Ball S, Busatto GF, David AS, et al. Cognitive functioning and GABAA/benzodiazepine receptor binding in schizophrenia: a 123I‐Iomazenil SPET study. Biological Psychiatry 1998; 43: 107–117
  • Schroder J, Bubeck B, Demish S, Sauer H. Benzodiazepine receptor distribution and diazepam binding in schizophrenia: an exploratory study. Psychiatry Research 1997; 68: 125–131
  • Simpson MDC, Slater P, Deakin JFW, Royston MC, Skan WJ. Reduced GABA uptake sites in the temporal lobe in schizophrenia. Neuroscience Letters 1989; 107: 211–215
  • Reynolds GP, Czudek C, Andrews HB. Deficit and hemispheric asymmetry of GABA uptake sites in hippocampus in schizophrenia. Biological Psychiatry 1990; 27: 1038–1044
  • Woo T‐U, Miller JL, Lewis DA. Schizophrenia and the parvalbumin‐containing class of cortical local circuit neurons. American Journal of Psychiatry 1997; 154: 1013–1015
  • Akbarian S, Kim JJ, Potkin SG, et al. Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Archives of General Psychiatry 1995; 52: 258–266
  • Tandon R. Cholinergic aspects of schizophrenia. British Journal of Psychiatry 1999; 37(Suppl.)7–11
  • Sarter M, Bruno JP. Abnormal regulation of corticopetal cholinergic neurons and impaired information processing in neuropsychiatric disorders. Trends in Neuroscience 1999; 22: 67–74
  • Tollefson GD, Beasley CM, Jr, Tran PV, et al. Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. American Journal of Psychiatry 1997; 154: 457–465
  • Bymaster FP, Calligaro DO, Falcone JF, et al. Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology 1996; 14: 87–96
  • McGeer PL, McGeer EG. Possible changes in striatal and limbic cholinergic systems in schizophrenia. Archives of General Psychiatry 1977; 34: 1319–1323
  • Domino EF, Krause RR, Bowers J. Various enzymes involved with putative neurotransmitters. Archives of General Psychiatry 1973; 29: 195–201
  • Karson GN, Casanova MF, Kleinman JE, Griffin WST. Choline acetyltransferase in schizophrenia. American Journal of Psychiatry 1993; 150: 454–459
  • Watanabe S, Nishikawa T, Takashima M, Toru M. Increased muscarinic cholinergic receptors in prefrontal cortices of medicated schizophrenics. Life Sciences 1983; 33: 2187–2196
  • Dean B, Crook JM, Opeskin K, Hill C, Keks N, Copolov DL. The density of muscarinic M1 receptors is decreased in the caudate‐ putamen of subjects with schizophrenia. Molecular Psychiatry 1996; 1: 54–58
  • Dean B, Crook JM, Pavey G, Opeskin K, Copolov DL. Studies on M1 and M2 muscarinic receptor mRNA in the human caudate‐putamen: no change in M1 receptor mRNA in schizophrenia. Molecular Psychiatry 2000; 5: 203–207
  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders4th edn. American Psychiatric Association, Washington 1994
  • Marsh M, McMahon HT. The structural era of endocytosis. Science 1999; 285: 215–220

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.