Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-16T17:05:32.188Z Has data issue: false hasContentIssue false

Schizophrenia – a Brain Disease? a Critical Review of Structural and Functional Cerebral Abnormality in the Disorder

Published online by Cambridge University Press:  02 January 2018

S. E. Chua
Affiliation:
Institute of Psychiatry, London
P. J. McKenna*
Affiliation:
Fulbourn Hospital, Cambridge
*
Dr McKenna, Fulbourn Hospital, Cambridge CB1 5EF

Abstract

Background

With genetic and neurochemical findings pointing to a biological aetiology, considerable effort has been devoted to finding direct evidence of brain abnormality in schizophrenia.

Method

T, MRI, post-mortem and functional imaging studies are reviewed to assess which structural and/or functional brain abnormalities have been consistently demonstrated.

Results

The only well-established structural abnormality in schizophrenia is lateral ventricular enlargement; this is modest and there is a large overlap with the normal population. There is no consensus on the presence of any localised structural abnormality from MRI and post-mortem studies, but the most promising findings concern temporal lobe limbic structures. Hypofrontality is not a well-replicated finding in schizophrenia under resting conditions, but the evidence is stronger for a selective association with negative symptoms. A number of studies have found hypofrontality under conditions of neuropsychological task activation. However, findings in these studies are divided and a recent methodologically sophisticated study has failed to confirm it, although this study suggested a decoupling of prefrontal and temporal function.

Conclusion

Schizophrenia is characterised by minor structural abnormality which, in the case of lateral ventricular enlargement, may be better understood as a risk factor than a causative lesion. The functional imaging findings are not transparent but suggest that, as a disorder, schizophrenia shows complex alterations in regional patterns of activity rather than any simple deficit in prefrontal function.

Type
Review Article
Copyright
Copyright © Royal College of Psychiatrists, 1995 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Altshuler, L. L., Conrad, A., Kovelman, J. A., et al (1987) Hippocampal pyramidal cell orientation in schizophrenia: a controlled neurohistologic study of the Yakovlev Collection. Archives of General Psychiatry, 44, 10941098.CrossRefGoogle ScholarPubMed
Altshuler, L. L., Casanova, M. F., Goldberg, T. E., et al (1990) The hippocampus and parahippocampus in schizophrenic, suicide and control brains. Archives of General Psychiatry, 47, 10291034.CrossRefGoogle ScholarPubMed
American Psychiatric Association (1980) Diagnostic and Statistical Manual of Mental Disorders (3rd edn) (DSM–III). Washington, DC: APA.Google Scholar
Andreasen, N. C., Nasrallah, H. A., Dunn, V., et al (1986) Structural abnormalities in the frontal system in schizophrenia. Archives of General Psychiatry, 43, 136144.CrossRefGoogle ScholarPubMed
Andreasen, N. C., Swayze, V. W., Flaum, M., et al (1990a) Ventricular enlargement in schizophrenia evaluated with computed tomographic scanning. Archives of General Psychiatry, 47, 10081015.CrossRefGoogle Scholar
Andreasen, N. C., Ehrardt, J. C., Swayze, V. W., et al (1990b) Magnetic resonance imaging of the brain in schizophrenia: the pathophysiologic significance of structural abnormalities. Archives of General Psychiatry, 47, 3544.CrossRefGoogle Scholar
Andreasen, N. C., Rezai, K., Alliger, R., et al (1992) Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Archives of General Psychiatry, 49, 943958.Google Scholar
Ariel, R. N., Golden, C. J., Berg, R. A., et al (1983) Regional cerebral blood flow in schizophrenics. Archives of General Psychiatry, 40, 258263.CrossRefGoogle ScholarPubMed
Arnold, S. E. (1994) Investigations of neuronal morphology and the neuronal cytoskeleton in the hippocampal region in schizophrenia. Neuropsychopharmacology, 10, 634S.Google Scholar
Arnold, S. E., Hyman, B. T., Van Hoesen, G. W., et al (1991) Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia. Archives of General Psychiatry, 48, 625632.CrossRefGoogle ScholarPubMed
Bajc, M., Medved, V., Basic, M., et al (1989) Cerebral perfusion inhomogeneities in schizophrenia demonstrated with single photon emission computed tomography and 99mTc-hexamethyl-propyleneamineoxime. Acta Psychiatrica Scandinavica, 80, 427433.Google Scholar
Barta, P. E., Pearlson, G. D., Powers, R. E., et al (1990) Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. American Journal of Psychiatry, 147, 14571462.Google Scholar
Bebbington, P. & Kuipers, L. (1988) Social influences on schizophrenia. In Schizophrenia: the Major Issues (eds P. Bebbington & P. McGuffin), pp. 201225. Oxford: Heinemann/Mental Health Foundation.Google Scholar
Benes, F. M. (1988) Post-mortem structural analyses of schizophrenic brain: study designs and the interpretation of data. Psychiatric Developments, 6, 213226.Google ScholarPubMed
Benes, F. M., Sorensen, I. & Bird, E. D. (1991) Reduced neuronal size in posterior hippocampus of schizophrenic patients. Schizophrenia Bulletin, 17, 597608.Google Scholar
Berman, K. F., Torrey, E. F., Daniel, D. G., et al (1992) Regional cerebral blood flow in monozygotic twins discordant and concordant for schizophrenia. Archives of General Psychiatry, 49, 927934.CrossRefGoogle ScholarPubMed
Bogerts, B. (1993) Recent advances in the neuropathology of schizophrenia. Schizophrenia Bulletin, 19, 431445.Google Scholar
Bogerts, B., Meertz, E. & Schoenfeldt-Bausch, R. (1985) Basal ganglia and limbic system pathology in schizophrenia: a morphometric study of brain volume shrinkage. Archives of General Psychiatry, 42, 784791.CrossRefGoogle Scholar
Bogerts, B., Ashtari, M., Degreef, G., et al (1990a) Reduced temporal limbic structure volumes on magnetic resonance imaging in first episode schizophrenia. Psychiatry Research: Neuroimaging, 35, 113.CrossRefGoogle Scholar
Bogerts, B., Falkai, P., Haupts, M., et al (1990b) Post-mortem volume measurements of limbic system and basal ganglia structures in chronic schizophrenics. Schizophrenia Research, 3, 295301.Google Scholar
Bogerts, B., Lieberman, J. A., Ashtari, M., et al (1993) Hippocampus–amygdala volumes and psychopathology in chronic schizophrenia. Biological Psychiatry, 33, 236246.Google Scholar
Bornstein, R. A., Schwartzkopf, S. B., Olson, S. C., et al (1992) Third-ventricle enlargement and neuropsychological deficit in schizophrenia. Biological Psychiatry, 31, 954961.CrossRefGoogle ScholarPubMed
Breier, A., Buchanan, R. W., Elkashef, A., et al (1992) Brain morphology and schizophrenia. Archives of General Psychiatry, 49, 921926.CrossRefGoogle ScholarPubMed
Brown, R., Colter, N., Corsellis, J. A. N., et al (1986) Postmortem evidence of structural brain changes in schizophrenia: differences in brain weight, temporal horn area, and parahippocampal gyrus compared with affective disorder. Archives of General Psychiatry, 43, 3642.CrossRefGoogle ScholarPubMed
Bruton, C. J., Crow, T. J., Frith, C. D., et al (1990) Schizophrenia and the brain: a prospective post-mortem study. Psychological Medicine, 20, 285304.CrossRefGoogle Scholar
Buchsbaum, M. S., DeLisi, L. E., Holcomb, H. H., et al (1984) Anteroposterior gradients in cerebral glucose use in schizophrenia and affective disorders. Archives of General Psychiatry, 41, 11591166.CrossRefGoogle ScholarPubMed
Buchsbaum, M. S., Nuechterlein, K. H., Haier, R. J., et al (1990) Glucose metabolic rate in normals and schizophrenics during the continuous performance test assessed by positron emission tomography. British Journal of Psychiatry, 156, 216227.Google Scholar
Buchsbaum, M. S., Haier, R. J., Potkin, S. G., et al (1992) Frontostriatal disorder of cerebral metabolism in never-medicated schizophrenic patients. Archives of General Psychiatry, 49, 935942.CrossRefGoogle Scholar
Busatto, G. F., Costa, D. C., Ell, P. J., et al (1994) Regional cerebral blood flow (rCBF) in schizophrenia during verbal memory activation: a 99mTc-HMPAO single photon emission tomography (SPET) study. Psychological Medicine, 24, 463472.CrossRefGoogle ScholarPubMed
Chapman, L. J. & Chapman, J. P. (1973) Disordered Thought in Schizophrenia. New York: Appleton-Century-Crofts.Google Scholar
Christison, G. W., Casanova, M. F., Weinberger, D. R., et al (1989) A quantitative investigation of hippocampal pyramidal cell size, shape, and variability of orientation in schizophrenia. Archives of General Psychiatry, 46, 10271032.CrossRefGoogle ScholarPubMed
Coffman, J. A. & Nasrallah, H. A. (1986) Magnetic brain imaging in schizophrenia. In The Neurology of Schizophrenia (eds H. A. Nasrallah & D. R. Weinberger), pp. 251266. Amsterdam: Elsevier.Google Scholar
Cohen, R. M., Semple, W. E., Gross, M., et al (1987) Dysfunction in a prefrontal substrate of sustained attention in schizophrenia. Life Sciences, 40, 20312039.Google Scholar
Colombo, C., Abbruzzese, M., Livian, S., et al (1993) Memory functions and temporal–limbic morphology in schizophrenia. Psychiatry Research: Neuroimaging, 50, 4556.CrossRefGoogle ScholarPubMed
Conrad, A. J., Abebe, T., Austin, R., et al (1991) Hippocampal pyramidal cell disarray in schizophrenia as a bilateral phenomenon. Archives of General Psychiatry, 48, 413417.CrossRefGoogle ScholarPubMed
Crawley, J. C., Crow, T. J., Johnstone, E. C., et al (1986) Dopamine D2 receptors in schizophrenia studied in vivo. Lancet, ii, 224225.CrossRefGoogle Scholar
Crow, T. J., Ball, J., Bloom, S. R., et al (1989) Schizophrenia as an anomaly of development of cerebral asymmetry: a post-mortem study and a proposal concerning the genetic basis of the disorder. Archives of General Psychiatry, 46, 11451150.Google Scholar
Dauphinais, I. D., DeLisi, L. E., Crow, T. J., et al (1990) Reduction in temporal lobe size in siblings with schizophrenia: a magnetic resonance imaging study. Psychiatry Research: Neuroimaging, 35, 135147.Google Scholar
David, G. B. (1957) The pathological anatomy of the schizophrenias. In Schizophrenia: Somatic Aspects (ed. Richter, D.), pp. 93130. Oxford: Pergamon.Google Scholar
Day, R. (1981) Life events and schizophrenia: the “triggering” hypothesis. Acta Psychiatrica Scandinavica, 64, 97122.CrossRefGoogle ScholarPubMed
Degreef, G., Ashtari, M., Bogerts, B., et al (1992) Volumes of ventricular system subdivisions measured from magnetic resonance images in first-episode schizophrenic patients. Archives of General Psychiatry, 49, 531537.Google Scholar
DeLisi, L., Buchsbaum, M. S., Holcomb, H. H., et al (1985) Clinical correlates of decreased anteroposterior gradients in positron emission tomography (PET) of schizophrenic patients. American Journal of Psychiatry, 142, 7881.Google ScholarPubMed
DeLisi, L., Dauphinais, I. & Gershon, E. S. (1988) Perinatal complications and reduced size of brain limbic structures in familial schizophrenia. Schizophrenia Bulletin, 14, 185191.CrossRefGoogle ScholarPubMed
DeLisi, L., Hoff, A. L., Schwartz, J. E., et al (1991) Brain morphology in first-episode schizophrenic-like patients: a quantitative magnetic resonance imaging study. Biological Psychiatry, 29, 159175.Google Scholar
DeMyer, M. K., Gilmor, R. L., Hendrie, H. C., et al (1988) Magnetic resonance image in schizophrenic and normal subjects: influence of diagnosis and education. Schizophrenia Bulletin, 14, 2132.CrossRefGoogle ScholarPubMed
Di Michele, V., Rossi, A., Stratta, P., et al (1992) Neuropsychological and clinical correlates of temporal lobe anatomy in schizophrenia. Acta Psychiatrica Scandinavica, 85, 484488.Google Scholar
Dolan, R. J., Bench, C. J., Liddle, P. F., et al (1993) Dorsolateral prefrontal cortex dysfunction in the major psychoses; symptom or disease specificity? Journal of Neurology, Neurosurgery and Psychiatry, 56, 12901294.Google Scholar
Dousse, M., Mamo, H., Ponsin, J. C., et al (1988) Cerebral blood flow in schizophrenia. Experimental Neurology, 100, 98111.Google Scholar
Ebmeier, K. P., Blackwood, D. H. R., Murray, C., et al (1993) Single-photon emission computed tomography with 99mTc-exametrazine in unmedicated schizophrenic patients. Biological Psychiatry, 33, 487495.CrossRefGoogle ScholarPubMed
Falkai, P. & Bogerts, B. (1986) Cell loss in the hippocampus of schizophrenics. European Archives of Psychiatry and Neurological Sciences, 236, 154161.Google Scholar
Falkai, P. & Bogerts, B. & Rozumek, M. (1988) Limbic pathology in schizophrenia: the entorhinal region – a morphometry study. Biological Psychiatry, 24, 515521.CrossRefGoogle Scholar
Farde, L., Wiesel, F.-A., Hall, H., et al (1987) No D2 receptor increase in PET study of schizophrenia. Archives of General Psychiatry, 44, 671672.Google Scholar
Farde, L., Wiesel, F.-A., Stone-Elander, S., et al (1990) D2 dopamine receptors in neuroleptic-naive schizophrenic patients: a positron emission tomography study with [11C]raclopride. Archives of General Psychiatry, 47, 213219.Google Scholar
Farkas, T., Wolf, A. P., Jaeger, J., et al (1984) Regional brain glucose metabolism in chronic schizophrenia: a positron emission transaxial tomographic study. Archives of General Psychiatry, 41, 293300.Google Scholar
Friston, K. J., Frith, C. D., Liddle, P. F., et al (1991) Investigating a network model of word generation with positron emission tomography. Proceedings of the Royal Society of London B, 244, 101106.Google Scholar
Friston, K. J., Frith, C. D., Liddle, P. F., et al (1993) Functional connectivity: the principal component analysis of large (PET) data sets. Journal of Cerebral Blood Flow and Metabolism, 15, 514.CrossRefGoogle Scholar
Frith, C. D., Friston, K. J., Herold, S., et al (1995) Regional brain activity in chronic schizophrenic patients during the performance of a verbal fluency task: evidence for a failure of inhibition in left superior temporal cortex. British Journal of Psychiatry, in press.Google Scholar
Geraud, G., Arne-Bes, M. C., Guell, A., et al (1987) Reversibility of hemodynamic hypofrontality in schizophrenia. Journal of Cerebral Blood Flow and Metabolism, 7, 912.CrossRefGoogle ScholarPubMed
Goldberg, T. E., Weinberger, D. R., Berman, K. F., et al (1987) Further evidence for dementia of prefrontal type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test. Archives of General Psychiatry, 44, 10081014.CrossRefGoogle ScholarPubMed
Gottesman, I. I. (1991) Schizophrenia Genesis: the Origins of Madness. New York: Freeman.Google Scholar
Gur, R. E., Skolnick, B. E. & Gur, R. C. (1983) Brain function in psychiatric disorders I: regional cerebral blood flow in medicated schizophrenics. Archives of General Psychiatry, 40, 12501254.CrossRefGoogle ScholarPubMed
Gur, R. E., Gur, R. C., Skolnick, B. E., et al (1985) Brain function in psychiatric disorders III: regional cerebral blood flow in unmedicated schizophrenics. Archives of General Psychiatry, 42, 329334.CrossRefGoogle ScholarPubMed
Gur, R. E., Resnick, S. M., Alavi, A., et al (1987) Regional brain function in schizophrenia I: a positron emission tomography study. Archives of General Psychiatry, 44, 119125.Google Scholar
Gur, R. E., Mozley, P. D., Resnick, S. M., et al (1991) Magnetic resonance imaging in schizophrenia. Archives of General Psychiatry, 48, 407412.Google Scholar
Gur, R. E., Jaggi, J. L., Shtasel, J., et al (1994) Cerebral blood flow in schizophrenia: effects of memory processing on regional activation. Biological Psychiatry, 35, 315.Google Scholar
Hall, L. D., Herrod, J., Carpenter, T. A., et al (1994) Magnetic resonance imaging in schizophrenia: a review of clinical and methodological issues. In Schizophrenia: Exploring the Spectrum of Psychosis (eds R. J. Ancill, S. Halliday & J. Higenbottam), pp. 115135. Chichester: Wiley.Google Scholar
Harvey, I., Ron, M. A., Du Boulay, G., et al (1993) Reduction of cortical volume in schizophrenia on magnetic resonance imaging. Psychological Medicine, 23, 591604.Google Scholar
Heckers, S., Heinsen, H., Heinsen, Y., et al (1990a) Morphometry of the parahippocampal gyrus in schizophrenics and controls: some anatomical considerations. Journal of Neural Transmission, 80, 151155.Google Scholar
Heckers, S., Heinsen, H., Heinsen, Y., et al (1990b) Limbic structures and lateral ventricle in schizophrenia: a quantitative postmortem study. Archives of General Psychiatry, 47, 10161022.CrossRefGoogle Scholar
Heckers, S., Heinsen, H., Heinsen, Y., et al (1991) Cortex, white matter, and basal ganglia in schizophrenia: a volumetric postmortem study. Biological Psychiatry, 29, 556566.Google Scholar
Heritch, A. J. (1990) Evidence for reduced and dysregulated turnover of dopamine in schizophrenia. Schizophrenia Bulletin, 16, 605615.CrossRefGoogle ScholarPubMed
Hietala, J., Syvalathi, E., Vaorio, K., et al (1994) Striatal D2 dopamine receptor characteristics in neuroleptic-naive schizophrenic patients studied with positron emission tomography. Archives of General Psychiatry, 51, 116123.Google Scholar
Hirsch, S. R. & Leff, J. P. (1975) Abnormalities in Parents of Schizophrenics. London: Oxford University Press.Google Scholar
Ingvar, D. H. & Franzen, G. (1974) Abnormalities of cerebral blood flow distribution in patients with chronic schizophrenia. Acta Psychiatrica Scandinavica, 50, 425462.Google Scholar
Jakob, H. & Beckmann, H. (1986) Prenatal developmental disturbances in the limbic allocortex in schizophrenics. Journal of Neural Transmission, 65, 303326.Google Scholar
Jernigan, T. L., Zisook, S., Heaton, R. K., et al (1991) Magnetic resonance imaging abnormalities in lenticular nuclei and cerebral cortex in schizophrenia. Archives of General Psychiatry, 48, 881890.Google Scholar
Jeste, D. V. & Lohr, J. B. (1989) Hippocampal pathologic findings in schizophrenia. Archives of General Psychiatry, 46, 10191024.Google Scholar
Johnstone, E. C., Crow, T. J., Frith, C. D., et al (1976) Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet, ii, 924926.Google Scholar
Johnstone, E. C., Owens, D. G. C., Crow, T. J., et al (1989) Temporal lobe structure as determined by nuclear magnetic resonance in schizophrenia and bipolar affective disorder. Journal of Neurology, Neurosurgery and Psychiatry, 52, 736741.Google Scholar
Jones, P. B., Harvey, I., Lewis, S. W., et al (1994) Cerebral ventricle dimensions as risk factors for schizophrenia and affective psychosis. Psychological Medicine, 24, 9951011.Google Scholar
Kawasaki, Y., Maeda, Y., Urata, K., et al (1993a) A quantitative magnetic resonance imaging study of patients with schizophrenia. European Archives of Psychiatry and Clinical Neuroscience, 242, 268272.Google Scholar
Kawasaki, Y., Maeda, Y., Suzuki, M., et al (1993b) SPECT analysis of regional cerebral blood flow changes in patients with schizophrenia during the Wisconsin Card Sorting Test. Schizophrenia Research, 10, 109116.Google Scholar
Kelsoe, J., Cadet, J. L., Pickar, D., et al (1988) Quantitative neuroanatomy in schizophrenia. Archives of General Psychiatry, 45, 533541.Google Scholar
Kirch, D. G. & Weinberger, D. R. (1986) Anatomical neuropathology in schizophrenia: post-mortem findings. In Handbook of Schizophrenia, Vol. 1, The Neurology of Schizophrenia (eds H. A. Nasrallah & D. R. Weinberger), pp. 325348. Amsterdam: Elsevier.Google Scholar
Kovelman, J. A. & Scheibel, A. B. (1984) A neurohistological correlate of schizophrenia. Biological Psychiatry, 19, 16011621.Google ScholarPubMed
Kraepelin, E. (1913) Dementia Praecox and Paraphrenia (trans. Barclay, R. M., 1919). Edinburgh: Livingstone.Google Scholar
Kurachi, M., Kobayashi, K., Matusbara, R., et al (1985) Regional cerebral blood flow in schizophrenic disorders. European Neurology, 24, 176181.Google Scholar
Lantos, P. (1988) The neuropathology of schizophrenia: a critical review of recent work. In Schizophrenia: the Major Issues (eds P. Bebbington & P. McGuffin), pp. 7389. Oxford: Heinemann/Mental Health Foundation.Google Scholar
Leff, J. (1991) Schizophrenia in the melting pot. Nature, 353, 693694.Google Scholar
Lewis, S. W. (1990) Computerised tomography in schizophrenia 15 years on. British Journal of Psychiatry, 157 (suppl. 9), 1624.CrossRefGoogle Scholar
Lewis, S. W., Ford, R. A., Syed, G. M., et al (1992) A controlled study of 99mTc-HMPAO single-photon emission ima$ in chronic schizophrenia. Psychological Medicine, 22, 27$ CrossRefGoogle Scholar
Liddle, P. F., Friston, K. J., Frith, C. D., et al ($ 1992) Patterns of cerebral blood flow in schizophrenia. British$ Journal of Psychiatry, 160, 179186.Google Scholar
Liddle, P. F., Herold, S., Fletcher, P., et al (1994) A PET $study of word generation in schizophrenia. Schizophrenia Research, 11, 168.Google Scholar
Marsh, L., Suddath, R. L., Higgins, N., et al (1994) Medial temporal lobe structures in schizophrenia: relationship of size to duration of illness. Schizophrenia Research, 11, 225238.Google Scholar
Martinot, J. L., Peron-Magnan, D., Huret, J. D., et al (1990) Striatal D2 dopaminergic receptors assessed with positron emission tomography and 76Br bromospiperone in untreated schizophrenic patients. American Journal of Psychiatry, 147, 4450.Google Scholar
Martinot, J. L., Paillere-Martinot, M. L., Lich, C., et al (1991) The estimated density of D2 striatal dopamine receptors in schizophrenia. A study with 76Br bromolisuride. British Journal of Psychiatry, 158, 346351.Google Scholar
Mathew, R. J., Duncan, G. C., Weinman, M. L., et al (1982) Regional cerebral blood flow in schizophrenia. Archives of General Psychiatry, 39, 11211124.CrossRefGoogle ScholarPubMed
Mathew, R. J., Wilson, W. H., Tant, S. R., et al (1988) Abnormal resting regional blood flow patterns and their correlates in schizophrenia. Archives of General Psychiatry, 45, 542549.Google Scholar
McGuffin, P., Asherson, P., Owen, M., et al (1994) The strength of the genetic effect: is there room for an environmental influence in the aetiology of schizophrenia. British Journal of Psychiatry, 164, 593599.Google Scholar
McKenna, P. J. (1994) Schizophrenia and Related Syndromes. Oxford: Oxford University Press.Google Scholar
McKenna, P. J., Tamlyn, D., Lund, C. E., et al (1990) Amnesic syndrome in schizophrenia. Psychological Medicine, 20, 967972.CrossRefGoogle ScholarPubMed
Nestor, P. G., Shenton, M. E., McCarley, R. W., et al (1993) Neuropsychological correlates of MRI temporal lobe abnormalities in schizophrenia. American Journal of Psychiatry, 150, 18491855.Google Scholar
Owens, D. G. C., Johnstone, E. C., Crow, T. J., et al (1985) Lateral ventricular size in schizophrenia: relationship to the disease process and its clinical manifestations. Psychological Medicine, 15, 2741.Google Scholar
Pakkenberg, B. (1987) Post-mortem study of chronic schizophrenic brains. British Journal of Psychiatry, 151, 744752.Google Scholar
Pakkenberg, B. (1990) Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. Archives of General Psychiatry, 47, 10231028.Google Scholar
Paulman, R. G., Devous, M. D., Gregory, R. R., et al (1990) Hypofrontality and cognitive impairment in schizophrenia: dynamic single-photon tomography and neuropsychological assessment of schizophrenic brain function. Biological Psychiatry, 27, 377399.CrossRefGoogle ScholarPubMed
Pilowsky, L. S. (1992) Understanding schizophrenia. British Medical Journal, 305, 327328.Google Scholar
Pilowsky, L. S., Costa, D. C., Ell, P. J., et al (1994) D2 dopamine receptor binding in the basal ganglia of antipsychotic-free schizophrenic patients: 123IBZM single photon emission tomography (SPET) study. British Journal of Psychiatry, 164, 1626.Google Scholar
Raine, A., Lencz, T., Reynolds, G., et al (1992) Evaluation of structural and functional prefrontal deficits in schizophrenia. Psychiatry Research: Neuroimaging, 45, 123137.Google Scholar
Raz, S. & Raz, N. (1990) Structural brain abnormalities in the major psychoses: a quantitative review of the evidence from computerised imaging. Psychological Bulletin, 108, 93108.Google Scholar
Raz, S., Raz, N. & Bigler, E. D. (1988) Ventriculomegaly in schizophrenia: is the choice of controls important? Psychiatry Research, 24, 7177.Google Scholar
Roberts, G. W. (1991) Schizophrenia: a neuropathological perspective. British Journal of Psychiatry, 158, 817.Google Scholar
Ron, M. A. & Harvey, I. (1990) The brain in schizophrenia. Journal of Neurology, Neurosurgery and Psychiatry, 53, 725726.Google Scholar
Rossi, A., Stratta, P., D'Albenzio, L., et al (1990) Reduced temporal lobe areas in schizophrenia. Biological Psychiatry, 27, 6168.Google Scholar
Rossi, A., Stratta, P., Mancini, F., et al (1994) Magnetic resonance imaging findings of amygdala-hippocampus shrinkage in male patients with schizophrenia. Psychiatry Research, 52, 4353.Google Scholar
Rubin, P., Holm, S., Friberg, L., et al (1991) Altered modulation of prefrontal and subcortical brain activity in newly diagnosed schizophrenia and schizophreniform psychosis: a regional cerebral blood flow study. Archives of General Psychiatry, 48, 987995.Google Scholar
Sagawa, K., Kawakatsu, S., Shibuya, I., et al (1990) Correlation of regional cerebral blood flow with performance on neuropsychological tests in schizophrenic patients. Schizophrenia Research, 3, 241246.Google Scholar
Saykin, A. J., Gur, R. C., Gur, R. E., et al (1991) Neuropsychological function in schizophrenia: selective impairment in memory and learning. Archives of General Psychiatry, 48, 618624.Google Scholar
Scheibel, A. B. & Kovelman, J. A. (1981) Disorientation of the hippocampal pyramidal cell and its processes in the schizophrenic patient. Biological Psychiatry, 16, 101102.Google Scholar
Schlaepfer, T. E., Harris, G. J., Tien, A. Y., et al (1994) Decreased regional cortical gray matter volume in schizophrenia. American Journal of Psychiatry, 151, 842848.Google ScholarPubMed
Seeman, P. (1987) Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse, 1, 133152.Google Scholar
Seidman, L. J., Yurgelin-Todd, D., Kremen, W. S., et al (1994) Relationship of prefrontal and temporal lobe MRI measures to neuropsychological performance in chronic schizophrenia. Biological Psychiatry, 35, 235246.Google Scholar
Shallice, T., Burgess, P. W. & Frith, C. D. (1991) Can the neuropsychological case-study approach be applied to schizophrenia. Psychological Medicine, 21, 661673.CrossRefGoogle ScholarPubMed
Shallice, T., Fletcher, P., Frith, C. D., et al (1994) Brain regions associated with acquisition and retrieval of verbal episodic memory. Nature, 368, 633635.Google Scholar
Shapiro, R. M. (1993) Regional neuropathology in schizophrenia: where are we? Where are we going. Schizophrenia Research, 10, 187239.Google Scholar
Shenton, M. E., Kikinis, R., Jolesz, F. A., et al (1992) Abnormalities of the left temporal lobe and thought disorder in schizophrenia. New England Journal of Medicine, 327, 604612.Google Scholar
Siegel, B. V., Buchsbaum, M. S., Bunney, W. E., et al (1993) Cortical–striatal–thalamic circuits and brain glucose metabolism in 70 unmedicated male schizophrenic patients. American Journal of Psychiatry, 150, 13251336.Google Scholar
Smith, G. N. & Iacono, W. G. (1986) Lateral ventricular size in schizophrenia and choice of control group. Lancet, i, 1450.Google Scholar
Smith, R. C., Baumgartner, R. & Calderon, M. (1987) Magnetic resonance imaging studies of the brains of schizophrenic patients. Psychiatry Research, 20, 3346.Google Scholar
Spitzer, R. L., Endicott, J. & Robins, E. (1978) Research Diagnostic Criteria for a Selected Group of Functional Disorders. New York: Biometric Research, New York State Psychiatric Institute.Google Scholar
Suddath, R. L., Casanova, M. F., Goldberg, T. E., et al (1989) Temporal lobe pathology in schizophrenia: a quantitative magnetic resonance imaging study. American Journal of Psychiatry, 146, 464472.Google Scholar
Suddath, R. L., Christison, G. W., Torrey, E. F., et al (1990) Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. New England Journal of Medicine, 322, 789794.Google Scholar
Szechtman, H., Nahmias, C., Garnett, S., et al (1988) Effect of neuroleptics on altered cerebral glucose metabolism in schizophrenia. Archives of General Psychiatry, 45, 523532.Google Scholar
Tamminga, C. A., Thaker, G. K., Buchanan, M., et al (1992) Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome. Archives of General Psychiatry, 49, 522530.CrossRefGoogle ScholarPubMed
Torrey, F. C. (1992) Are we overestimating the genetic contribution to schizophrenia? Schizophrenia Bulletin, 18, 159170.Google Scholar
Tune, L. E., Wong, D. F. & Pearlson, G. D. (1992) Elevated dopamine D2 receptor density in 23 schizophrenic patients: a positron emission tomography study with [11C]N-methylspiperone. Schizophrenia Research, 6, 147.Google Scholar
Uematsu, M. & Kaiya, H. (1989) Midsagittal cortical pathomorphology of schizophrenia: a magnetic resonance imaging study. Psychiatry Research, 30, 1120.Google Scholar
Van Horn, J. D. & McManus, I. C. (1992) Ventricular enlargement in schizophrenia: a meta-analysis of studies of the ventricle: brain ratio (VBR). British Journal of Psychiatry, 160, 687697.Google Scholar
Volkow, N. D., Wolf, A. P., Van Gelder, P., et al (1987) Phenomenological correlates of metabolic activity in 18 patients with chronic schizophrenia. American Journal of Psychiatry, 144, 151158.Google Scholar
Waddington, J. L. (1990) Sight and insight: regional cerebral metabolic activity in schizophrenia visualised by positron emission tomography, and competing neurodevelopmental perspectives. British Journal of Psychiatry, 156, 615619.Google Scholar
Warkentin, S., Nilsson, A., Risberg, J., et al (1990) Regional cerebral blood flow in schizophrenia: repeated studies during a psychotic episode. Psychiatry Research: Neuroimaging, 35, 2738.Google Scholar
Weinberger, D. R., Torrey, E. F., Neophytides, A. N., et al (1979) Lateral cerebral ventricular enlargement in schizophrenia. Archives of General Psychiatry, 36, 735739.Google Scholar
Weinberger, D. R., Berman, K. F. & Zec, R. F. (1986) Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia: I. Regional cerebral blood flow evidence. Archives of General Psychiatry, 43, 114124.Google Scholar
Weinberger, D. R., Berman, K. F. & Illowsky, B. P. (1988) Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia: III. A new cohort and evidence for a monoaminergic mechanism. Archives of General Psychiatry, 45, 609615.Google Scholar
Wiesel, F. A., Wik, G., Sjogren, G., et al (1987) Regional brain glucose metabolism in drug free schizophrenic patients and clinical correlates. Acta Psychiatrica Scandinavica, 76, 628641.Google Scholar
Wolkin, A., Angrist, B., Wolf, A., et al (1988) Low frontal glucose utilization in chronic schizophrenia: a replication study. American Journal of Psychiatry, 145, 251253.Google Scholar
Wolkin, A., Sanfilipo, M., Wolf, A. P., et al (1992) Negative symptoms and hypofrontality in chronic schizophrenia. Archives of General Psychiatry, 49, 959965.Google Scholar
Wong, D. F., Wagner, H. N., Tune, L. E., et al (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science, 234, 15581563.Google Scholar
World Health Organization (1977) The Ninth Revision of the International Statistical Classification of Diseases, Injuries and Causes of Death (ICD–9). Geneva: WHO.Google Scholar
Young, A. H., Blackwood, D. H. R., Roxburgh, H., et al (1991) A magnetic resonance imaging study of schizophrenia. British Journal of Psychiatry, 158, 158164.Google Scholar
Zipursky, R. B., Lim, K. O., Sullivan, E. V., et al (1992) Widespread cerebral gray matter volume deficits in schizophrenia. Archives of General Psychiatry, 49, 195205.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.