In the past two decades neurobiological research into schizophrenia has seen a shift of emphasis from the dopaminergic pharmacology of subcortical systems to areas of abnormality inferred from direct studies, i.e. frontal cortex and medial temporal lobe. Recent research has tried to integrate morphological abnormalities with neurochemical and pharmacological data. These integrated approaches have uncovered neurochemical systems other than dopamine which are of importance. This approach has led to greater understanding of neurochemical mechanisms associated with these abnormalities and may provide novel approaches for therapeutic intervention.
Andreasen N., Nasrallah H., Dunn V., Olson S.C., Grove W.M., Ehrhardt J.C., Coffmann J.A., Crossett J H W (1986) Structural abnormalities in the frontal system in schizophrenia. Arch Gen Psychiatr43: 136-144
2.
Benes F.M., Davidson J., Bird E.D. (1986) Quantitative cytoarchitectural studies of cerebral cortex of schizophrenia. Arch Gen Psychiatr43: 31-35
3.
Berman K.F., Weinberger D.R. (1990) Lateralisation of cortical function during cognitive tasks: Regional cerebral blood flow studies of normal individuals and patients with schizophrenia. J Neurol, Neurosurg Psychiatr53: 150-160
4.
Berman K.F., Torrey E.F., Daniel D.G., Weinberger D.R. (1989) Prefrontal cortical blood flow in monozygotic twins concordant and discordant for schizophrenia. Schizophrenia Res2: R9p
5.
Bird E.D., Spokes E G S, Iversen L.L. (1979) Increased dopamine concentrations in limbic areas of brain from patients dying with schizophrenia. Brain102: 347-360
6.
Bogerts B., Meertz E., Schonfeldt-Bausch R. (1985) Basal ganglia and limbic system pathology in schizophrenia: A morphometric study of brain volume and shrinkage. Arch Gen Psychiatr42: 784-791
7.
Brown R., Colter N., Corsellis J A N, Crow T.J., Frith C.D., Jagoe R., Johnstone E.C., Marsh I. (1986) Post-mortem evidence of structural brain changes in schizophrenia: Differences in brain weight, temporal horn and parahippocampal gyrus compared with affective disorder. Arch Gen Psychiatr43: 36-42
8.
Brozowski T.J., Brown R.M., Rosvold H.E., Goldman P.S. (1979) Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science205: 929-932
9.
Bunney B.S., Aghajanian G.K. (1976) Dopamine and norepinephrine innervated cells in the rat prefrontal cortex: pharmacological differentiation using microiontophoretic techniques. Life Sci19: 1783-1972
10.
Camps M., Cortes R., Gueye B., Probst A., Palacios J.M. (1989) Dopamine receptors in the human brain: autoradiographic distribution of D2 sites. Neuroscience28: 274-296
11.
Carlsson A., Lindquist M. (1963) Effect of chlorpromazine and haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol20: 140-144
12.
Carruthers B., Dawbarn D., de Quick M., Emson PC, Hunter J., Reynolds G.P. (1984) Changes in neuropeptide content of amygdala in schizophrenia. Br J Pharmacol81: 139P
13.
Carter C.J., Pycock C.J. (1978) Studies on the role of catecholamines in the frontal cortex. Br J Pharmacol62: 402p
14.
Chavez-Noriega L., Patino P., Garcia-Munoz M. (1986) Excitability changes induced in the striatal dopamine containing terminals following frontal cortex stimulation. Brain Res379: 300-306
15.
Christie M.J., Rowe P.J., Beart D.M. (1986) Effect of excitotoxic lesions in the medial prefrontal cortex on cortical and subcortical catecholamine turnover in the rat. J Neurochem47: 1593-1597
16.
Christison G.W., Casanova M.F., Weinberger D.R., Rawlings R., Kleinmann J. (1989) A quantitative investigation of hippocampal pyramidal cell size, shape and variability of orientation in schizophrenia. Arch Gen Psychiatr46: 1027-1032
17.
Chun J J M, Makamura M.J., Shatz C.J. (1987) Transient cells of the developing mammalian telencephalon are peptide immunoreactive neurons. Nature325: 617-620
18.
Clow A., Theodoron A., Jenner P., Marsden C.D. (1980) Changes in rat striatal dopamine turnover and receptor activity during one year's neuroleptic administration. Eur J Pharmacol63: 135-144
19.
Cortes R., Gueye B., Pazos A., Probst A., Palacios J. (1989) Dopamine receptors in human brain autoradiographic distribution of D1 sites. Neuroscience28: 263-273
20.
Costall B., Naylor R.J. (1976) Mesolimbic and extrapyramidal sites for the mediation of stereotyped behaviour patterns and hyperactivity by amphetamine and apomorphine in the rat. In Ellinwood E H, Kibey M M (eds), Cocaine and other stimulants . Plenum Press, New York, pp. 47-76
21.
Crow T.J., Owen F., Cross A.J. et al. (1981) Neurotransmitter enzymes and receptors in post-mortem brain in schizophrenia ; evidence that an increase in D2 receptors is associated with type I syndrome. In Riederer P, Usdin E (eds), Transmitter biochemistry of human brain tissue. Macmillan, London
22.
Crow T.J., Ball J., Bloom S.R., Brown R., Bruton C.D., Colter N., Frith C.D., Johnstone E.C., Owens D G C, Roberts G.W. (1989) Schizophrenia as an anomaly of development of cerebral asymmetry: a post-mortem study and a proposal concerning the genetic basis of the disease. Arch Gen Psychiatr46: 1145-1150
23.
Deakin J F W, Slater P., Simpson M D C, Gilchrist A.C., Skan W.J., Royston M.C., Reynolds G.P., Cross A.J. (1989) Frontal cortical and left temporal glutamatergic dysfunction in schizophrenia. J Neurochem52: 1781-1786
24.
Deakin J F W, Simpson M D C, Royston M.C., Slater P., McKenna P.J., Brophy J. (1991) Social signalling and schizophrenia: The significance of neurochemical and morphological abnormalities of the basolateral circuit . Schizophrenia Res4: 357-360
25.
Deutsch S.I., Weizman A., Goldman M.I., Morihisa J.M. (1988) The sigma receptor: a novel site implicated in psychosis and antipsychotic drug efficacy. Clin Neuropharmacol11: 105-119
26.
Emson P.C., Koob F.G. (1978) The origin and distribution of dopamine containing afferents to the rat frontal cortex. Brain Res142: 249-267
27.
Fagg G.E., Foster A.C. (1984) Amino acid neurotransmitters and their pathways in the mammalian central nervous system. Neuroscience9: 701-727
28.
Falkai P., Bogerts B. (1986) Cell loss in the hippocampus of schizophrenia. Eur Arch Psychiatr Neurol Sci236: 154-161
29.
Falkai P., Bogerts B., Rozumek M. (1988) Limbic pathology in schizophrenia: The entorhinal region—a morphometric study. Biol Psychiatr24: 515-521
30.
Falkai P., Bogerts B., Roberts G.W., Crow T.J. (1988) Measurement of the alpha-cell migration in the entorhinal region: a marker for the developmental disturbances in schizophrenia . Schizophrenia Res1: 157-158
31.
Farde L., Wiesel F.A., Stone-Elander S., Halldin C., Nordstrom A.L., Hall H., Sedvall G. (1990) D2 dopamine receptors in neuroleptic naive schizophrenic patients. Arch Gen Psychiatr47: 213-219
32.
Farmery S.M., Owen F., Poulter M., Crow T.J. (1985) Reduced high affinity cholecystokinin binding in hippocampus and frontal cortex of schizophrenic patients. Life Sci36: 473-477
33.
Ferrier I.N., Roberts G.W., Crow T.J., Johnstone E.C., Owens D G C, Lee Y.C., O'Shaughessy D., Adrian T.E., Polak J.M., Bloom S.R. (1983) Reduced cholecystokinin like and somatostatin like immunoreactivity in limbic lobe is associated with negative symptoms in schizophrenia . Life Sci33: 475-482
34.
Gray J.A. (1982) The neuropsychology of anxiety: an enquiry into the functions of the septo-hippocampal system. Oxford University Press, Oxford/New York
35.
Harrison P.J., McLaughlin D., Kerwin R.W. (1991) Decreased hippocampal expression of a glutamate receptor gene in schizophrenia. Lancet337: 450-452
36.
Herman J.P., Guilloneau D., Dantzer R. (1982) Differential effects of inescapable foot shocks and of stimuli previously paired with inescapable foot shock on dopamine turnover in cortical and limbic areas of the rat. Life Sci30: 2207-2214
37.
Hokfelt T., Skirboll L., Reyfeld J.G., Goldstein M., Markey K., Dann O. ( 1984) A subpopulation of mesencephalic dopamine neurones projecting to limbic areas contain a cholecystokinin like peptide: evidence from immunohistochemistry combined with retrograde tracing. Neuroscience5: 2093-2124
38.
Hollmann M., O'Shea-Greenfield A., Rogers S.W., Heinemann S (1989) Cloning by functional expression of a member of the glutamate receptor family. Nature342: 643-648
39.
Iversen S.D. (1971) The effect of surgical lesions to the frontal cortex and substantia nigra on amphetamine responses in rats. Brain Res31: 295-311
40.
Jakob H., Beckmann H. (1986) Prenatal developmental disturbances in the limbic allocortex in schizophrenics. J Neurol Transmission65: 303-326
41.
Jaskiw GE, Karoum F., Freed WJ, Kleinman JE, Weinberger D.R. (1987) Effect of medial prefrontal cortex lesions on dopamine turnover and dopamine agonist induced behaviours. Soc Neurosci Abstr13: 599p
42.
Jeste D., Lohr J.B. (1989) Hippocampal pathologic findings in schizophrenia . A morphometric study. Arch Gen Psychiatr46: 1019-1024
43.
Johnstone E.C., Crow T.J., Frith C.D., Husband J., Kreel L. (1976) Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancetii: 924-926
44.
Johnstone E.C., Crow T.J., Frith C.D., Carney M W P, Price J.S. (1978) Mechanism of the antipsychotic effect in acute schizophrenia. Lanceti: 848-851
45.
Joyce E.M., Stinus L., Iversen S.D. (1983) Effect of injections of 6-OHDA into either nucleus accumbens septi or frontal cortex on spontaneous and drug induced activity . Neuropharmacology22: 1141-1145
46.
Kelly P.H., Seviour P.W., Iversen S.D. (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum . Brain Res94: 507-522
47.
Kerwin R.W. (1987) Pathology, phenomenology and the dopamine hypothesis of schizophrenia. Br J Psychiatr152: 141 (letter)
48.
Kerwin R.W., Beats B. (1990) Increased forskolin binding in left parahippocampal gyrus and CA1 region in post mortem schizophrenic brain determined by quantitative autoradiography. Neurosci Lett118: 164-168
49.
Kerwin R.W., Patel S., Meldrum B.S., Czudek C., Reynolds G.P. (1988) Asymmetrical loss of glutamate receptor subtype in left hippocampus in schizophrenia. Lancet1: 583-584
50.
Kerwin R.W., Patel S., Meldrum B.S. (1990) Autoradiographic localization of the glutamate receptor system in control and schizophrenia post-mortem hippocampal formation . Neuroscience39: 25-32
51.
Kerwin R.W., Robinson P., Stephenson J. (1992) Autoradiographic analysis of cholecystokinin receptors in post-mortem schizophrenic temporal lobe. Psychol Med22: 37-44
52.
Kohler C., Chan-Palay V.C. (1988) Cholecystokinin octapeptide (CCK-8) receptors in the hippocampal region: a comparative in vitro autoradiographic study in the rat, monkey and the post-mortem human brain. Neurosci Lett90: 51-56
53.
Kornhuber J., Mack-Burkhardt F., Riederer P., Hebenstreit P.F., Reynolds G.P., Andrews H.B., Beckmann H. (1989) 3H·MK801 binding sites in post-mortem brain regions of schizophrenic patients. J Neural Transmission77: 231-236
54.
Kovelman J.A., Scheibel A. (1984) A neurohistological correlate of schizophrenia . Biol Psychiatr19: 1601-1621
55.
Leccesse A.P., Lyness W.P. (1987) Lesions of dopamine neurons in the medial prefrontal cortex: Effects on self administration of amphetamine and dopamine synthesis in the brain of the rat. Neuropharmacology26: 1303-1308
56.
Lee T., Seeman P. (1980) Elevation of brain neuroleptic dopamine receptors in schizophrenia. Am J Psychiatr137: 191-197
57.
Lee T., Seeman P., Tourtelotte W., Farley I., Hornykiew C.Z. (1978) Binding of 3H· apomorphine in schizophrenic brains . Nature274: 897-900
58.
Lindvall O., Bjorklund A., Divac I. (1978) Organisation of catecholamine neurons projecting to the frontal cortex in the rat. Brain Res142: 1-24
59.
Mackay A V P, Iversen L.L., Rossor M., Spokes E., Bird E., Arregui A., Creese I., Snyder S.H. (1982) Increased brain dopamine and dopamine receptors in schizophrenia. Arch Gen Psychiatr39: 991-997
60.
Marsden C.D., Tarsy D., Baldessarini R.J. (1975) In Benson D F, Blumer D (eds), Psychiatric aspects of neurologic disease. Grune & Stratton, New York, pp. 219-265
61.
Martin-Iversen M.T., Szostak C., Fibiger H.C. (1986) 6-hydroxydopamine lesions of the medial prefrontal cortex fail to influence intravenous self administration of cocaine. Psychopharmacology 88: 310-314
62.
Martinot J.L., Pailiere-Martinot C., Loch H., Hardy P., Poirier M.F., Mazoyer B., Beaufils B., Maziere B., Allilaire J.F., Syrota A. (1991) The estimated density of D2 striatal receptors in schizophrenia: A study with positron emission tomography and 76Bromolisuride . Br J Psychiatr158: 346-351
63.
Mattson M.P., Dou P., Kater S.B. (1988) Outgrowth regulating actions of glutamate in isolated hippocampal pyramidal neurones. J Neurosci8: 2087-2100
64.
Montgomery S., Green M C D (1988) The use of cholecystokinin in schizophrenia: a review. Psychol Med18: 593-603
65.
Nemeroff C.B., Youngblood W.W., Manberg P.J., Prange A., Kiza J.S. (1983) Regional brain concentrations of neuropeptides in Huntington's chorea and schizophrenia. Science221: 972-975
66.
Perry R.H., Dockray G.J., Dimaline R., Perry E.K., Blessed G., Tomlinson B.E. (1981) Neuropeptides in Alzheimer's disease, depression and schizophrenia. J Neurol Sci51 : 465-472
67.
Pycock C.J., Carter C.J., Kerwin R.W. (1979) Possible involvement of frontal cortical catecholamine systems in the regulation of neurotransmitter system at subcortical sites . Biochem Soc Trans7: 140-143
68.
Pycock C.J., Carter C.J., Kerwin R.W. (1980) Effect of 6-hydroxydopamine lesions of the medial prefrontal cortex on neurotransmitter systems in subcortical sites in the rat. J Neurochem34: 91-99
69.
Pycock C.J., Kerwin R.W., Carter C.J. (1980) Effect of lesion of cortical dopamine terminals on subcortical dopamine receptors in rats. Nature286: 74-77
70.
Owen F., Crow T.J., Poulter M., Cross A.J., Longden A., Riley G.J. (1978) Increased dopamine receptor sensitivity in schizophrenia . Lancetii: 223-225
71.
Randrup A., Munkvad I. (1967) Stereotyped activities produced by amphetamine in several animal species and man. Psychopharmacologia11: 300-310
72.
Reibaud M., Blanc G., Studler J.M., Glowinski J., Tassin J.P. (1984) Non-DA prefronto-cortical dopamine afferents modulate D1 receptors in the nucleus accumbens. Brain Res305: 43-50
73.
Reynolds G.P. (1983) Increased concentrations and lateral asymmetry of amygdalar dopamine in schizophrenia. Nature305: 527-529
74.
Reynolds G.P. (1988) The post-mortem neurochemistry of schizophrenia . Psychol Med18: 793-797
75.
Reynolds G.P., Czudek C., Andrews H.B. (1990) Deficit and hemispheric asymmetry of GABA uptake sites in the hippocampus in schizophrenia. Biol Psychiatr27: 1038-1044
76.
Roberts G.W. (1991) Schizophrenia: A neuropathological perspective . Br J Psychiatr158: 8-17
77.
Roberts G.W., Bruton C.J. (1990) Annotation: Notes from the Graveyard: Neuropathology and schizophrenia. Neuropathol Appl Biol16: 3-16
78.
Roberts G.W., Ferrier I.N., Lee Y., Crow T.J., Johnstone E.C., Owens D G C, Barcaresa-Hamilton A.J., MacGregor G., O'Shaughessy D., Polak T.M., Bloom S.R. (1983) Peptides, the limbic lobe and schizophrenia. Brain Res288: 199-211
79.
Roberts G.W., Woodhouse P.L., Polak J.M., Crow T.J. (1984) Distribution of neuropeptides in the limbic system of the rat: The hippocampus. Neuroscience11: 37-77
80.
Roberts G.W., Colter N., Lofthouse R., Bogerts B., Zech N., Crow T.J. (1986) Gliosis in schizophrenia. Biol Psychiatr21: 1043-1050
81.
Royston M.C., Simpson M D C (1991) Post-mortem neurochemistry of schizophrenia. In Kerwin R, Dawbarn D, McCulloch J, Tamminga C (eds), Neurobiology and psychiatry vol I. Cambridge University Press, pp. 1-13
82.
Seeman P., Bzowej N.H., Guan H.C., Bergeron C., Reynolds G.P., Bird E.D., Riederer P., Jellinger K., Tourtellette W. (1987) Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimers, Parkinsons and Huntingtons Disease. Neuropsychopharmacology1: 5-15
83.
Schenk S., Horger B.A., Peltier R., Shelton S. (1991) Supersensitivity to the reinforcing effects of cocaine following 6-hydroxydopamine lesions to the medial prefrontal cortex in rats. Brain Res543: 227-235
84.
Shelton R.C., Karson C.N., Doran A.R., Pickar D., Bigelow L., Weinberger D.R. (1988) Cerebral structural pathology in schizophrenia: evidence for a selective prefrontal cortical deficit. Am J Psychiatr145: 154-163
85.
Simpson M D C, Royston M.C., Slater P., Deakin J F W (1990a) Phencyclidine and sigma receptor abnormalities in schizophrenic post-mortem brain. Schizophrenia Res3: 32p
86.
Simpson M D C, Slater P., Deakin J F W, Royston M.C., Skan M. ( 1990b) Reduced GABA uptake sites in the temporal lobe in schizophrenia . Neurosci Lett107: 211-215
87.
Snyder S.H., Bannerjee S., Yamamura H., Greenberg D. (1974) Drugs neurotransmitters and schizophrenia. Science184: 1243-1253
88.
Storm-Mathisen J. (1981) Glutamate in hippocampal pathways. In Dichiari G, Gessa G L (eds), Glutamate as a neurotransmitter. Raven Press , New York, pp. 1598-6030
89.
Suddath R.I., Christison G.W., Torrey E.F., Weinberger D.R. (1990) Cerebral anatomical abnormalities in monozygotic twins discordant for schizophrenia. New Engl J Med322: 789-794
90.
Suga I., Kobayashi T., Ogata H., Toru M. ( 1990) Increased 3H·MK801 binding sites in post-mortem brain of chronic schizophrenic patients. Proc 17th Coll Int Neuropsychopharmacology82: 28
91.
Svendson D.N., Langlais P.J., Benes F.M., Bird E.D. (1986) Monoamine levels in the left and right amygdaloid complex of schizophrenic post-mortem brain tissue. In Shagass C. et al. (eds), Biological psychiatry. Elsevier, Amsterdam, pp. 1115-1117
92.
Tassin J.P., Stinus L., Simon H., Blanc G., Thierry AM, Le Moal M., Cardo B., Glowinski J. (1978) Relationship between the locomotor activity induced by A10 lesions and the destruction of the front-cortico dopaminergic innervation of the rat. Brain Res141: 168-173
93.
Ungerstedt U. (1971) Stereotoxic mapping of the monoamine pathways in the rat brain. Acta Physiol Scand83 (Suppl. 367): 1-48
94.
Weinberger DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatr44: 660-667
95.
Weinberger D., Berman K.F. (1988) Speculation on the meaning of cerebral metabolic hypofrontality in schizophrenia. Schizophrenia Bull14: 157-168
96.
Weinberger D.R., Torrey E.F., Neophytides A.N., Wyatt J.R. (1979) Structural abnormalities in the cerebral cortex of chronic schizophrenic patients. Arch Gen Psychiatr36: 935-939
97.
Weinberger D.R., Berman K.F., Zec R.F. (1986) Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. Arch Gen Psychiatr43: 114-124
98.
Weissman A.D., Casanova M.F., Kleinman J.E., London E., Desouza E.B. (1991) Selective losses of cerebral cortical stigma but not PCP binding sites in schizophrenia. Biol Psychiatr29: 41-54
99.
Wong D.F., Wagner H.N., Tune L.E., Wong D.F., Wagner H.N., Tune L.E., Dannals R.F., Pearlson G.D., Links J.M., Tamminga, C.A., Broussole E.P., Ravert H.T., Wilson A.N., Toung T., Malat J., Williams J.A., O'Tuama L.A., Snyder S.H., Kuhar M.J., Gjedde A. (1986) Positron emission tomography reveals D2 receptors in drug naive schizophrenics. Science234: 1558-1563
