Hostname: page-component-7c8c6479df-p566r Total loading time: 0 Render date: 2024-03-28T09:54:11.029Z Has data issue: false hasContentIssue false

Schizophrenia: A Neuropathological Perspective

Published online by Cambridge University Press:  02 January 2018

G. W. Roberts*
Affiliation:
Department of Anatomy and Cell Biology, St Mary's Hospital Medical School, Norfolk Place, London W2 1PG

Abstract

It is probable that all schizophrenics have abnormalities in the medial temporal lobe, which differ in degree but not in kind. The structures of the medial temporal lobe are believed to have a crucial role in the integration and processing of the output from the association cortex. Dysfunction of this system could result in the clinical symptoms that form the core of the schizophrenia syndrome. The structural differences appear to fit the profile of a disturbance in the normal pattern of brain development. The asymmetrical patterns of normal brain development explain how such a disturbance simultaneously affecting both hemispheres could, disproportionately, affect the left (dominant) hemisphere. Epidemiological and pathological evidence points to aberrant genetic mechanisms as being the cause of the developmental anomaly in the majority of cases; environmental factors probably play a minor role. Despite the great progress made in solving the enigma of the structural changes in the brains of schizophrenics, the cause(s) of the changes – the aberrant genetic mechanism controlling brain development – may prove difficult to define.

Type
Review Article
Copyright
Copyright © The Royal College of Psychiatrists 

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

Amaral, D. G., Insausti, R. & Cowan, W. M. (1987) The entorhinal cortex of the monkey: I cytoarchitectonic organisation. Journal of Comparative Neurology, 264, 326355.Google Scholar
Bogerts, B., Meertz, E. & Schonfeldt-Bausch, R. (1985) Basal ganglia and limbic system pathology in schizophrenia: a morphometric study of brain volume and shrinkage. Archives of General Psychiatry, 42, 784791.Google Scholar
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.Google Scholar
Bruton, C. J., Crow, T. J., Frith, C. D., et al (1990) Schizophrenia and the brain: a prospective clinico-neuropathology study. Psychological Medicine, 20, 285304.CrossRefGoogle Scholar
Burn, J., Povey, S. & Boyd, Y. (1986) Duchenne muscular dystrophy in one of monozygotic twin girls. Journal of Medical Genetics, 23, 494500.Google Scholar
Burn, J. & Corney, G. (1988) Zygosity determination and types of twinning. In Twinning and Twins (eds I. McGillivray et al), pp. 725. London: Wiley.Google Scholar
Chi, Je G., Dooling, E. C. & Gilles, F. H. (1977) Gyral development of human brain. Annals of Neurology, 1, 8693.Google Scholar
Christison, G. W., Casanova, M. F., Weinberger, D. R., et al (1989) A quantitative investigation of parahippocampal pyramidal cell size, shape and variability of orientation in schizophrenia. Archives of General Psychiatry, 46, 10271032.Google Scholar
Crow, T. J. (1980) Molecular pathology of schizophrenia. More than one disease process? British Medical Journal, i, 6669.Google Scholar
Crow, T. J. (1983) Is schizophrenia an infectious disease? Lancet, i, 173175.Google Scholar
Crow, T. J. & Johnstone, E. C. (1987) Schizophrenia: nature of the disease process and its biological correlates. Handbook of Physiology – The Nervous System, V (ed. F. Plum), pp. 843869. Baltimore: American Physiological Society.Google 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 disease. Archives of General Psychiatry, 46, 1145–50.Google Scholar
Corsellis, J. A. N. (1976) Psychoses of obscure pathology. In Greenfields Neuropathology (ed. W. Blackwood & J. A. N. Corsellis), pp. 903915. London: Edward Arnold.Google Scholar
Davison, K. & Bagley, C. R. (1969) Schizophrenia-like psychoses associated with organic disorders of the central nervous system – a review of the literature. In Current Problems in Neuropsychiatry (ed. R. N. Hetherington), British Journal of Psychiatry Special Publication No. 4, pp. 113184. Kent: Headley Bros.Google Scholar
Drevets, W. C. & Rubin, E. H. (1989) Psychotic symptoms and the longitudinal course of senile dementia of the Alzheimer type. Biological Psychiatry, 25, 3948.Google Scholar
Falkai, P. & Bogerts, B. (1986) Cell loss in the hippocampus of schizophrenics. European Archives of Psychiatry and Neurological Sciences, 236, 154161.CrossRefGoogle ScholarPubMed
Falkai, P., Bogerts, B., Roberts, G. W., et al (1988a) Measurement of the alpha-cell-migration in the entorhinal region: a marker for the developmental disturbances in schizophrenia? Schizophrenia Research, 1, 157158.Google Scholar
Falkai, P., Bogerts, B. & Rozumek, M. (1988b) Limbic pathology in schizophrenia: the entorhinal region – a morphometric study. Biological Psychiatry, 24, 515521.Google Scholar
Farmer, A., Jackson, R., McGuffin, P., et al (1987) Cerebral ventricular enlargement in chronic schizophrenia: consistencies and contradictions. British Journal of Psychiatry, 150, 324330.Google Scholar
Frith, C. D. & Done, D. J. (1988) Towards a neuropsychology of schizophrenia. British Journal of Psychiatry, 153, 437443.Google Scholar
Gilles, F. H. & Green, B. E. (1985) Neuropathologic indicators of abnormal development. In Prenatal and Perinatal Factors Associated with Brain Disorders. NIH Publication No. 85–1149 (ed. J. M. Freeman). Bethesda: NIH.Google Scholar
Goodman, R. (1988) Are complications of pregnancy and birth causes of schizophrenia? Developmental Medicine and Child Neurology, 30, 391406.Google Scholar
Goodman, R. (1989) Neuronal misconnections and psychiatric disorder. Is there a link? British Journal of Psychiatry, 154, 292–229.CrossRefGoogle ScholarPubMed
Gottesman, I. I. & Bertelsen, A. (1989) Confirming unexpressed genotypes for schizophrenia. Archives of General Psychiatry, 46, 862867.Google Scholar
Haug, J. O. (1962) Pneumoencephalographic studies in mental disease. Acta Psychiatrica Scandinavica, 38, 1114.Google Scholar
Illowsky, B. N., Juliano, D. M., Bigleow, L. B., et al (1988) Stability of CT scan findings in schizophrenia: results of an 8 year follow-up study. Journal of Neurology, Neurosurgery and Psychiatry, 51, 209213.Google Scholar
Insausti, R., Amaral, D. G. & Cowan, W. M. (1987a) The entorhinal cortex of the monkey: II cortical afferents. Journal of Comparative Neuroloey, 264, 356395.Google Scholar
Insausti, R., Amaral, D. G. & Cowan, W. M. (1987b) The entorhinal cortex of the monkey: II subcortical afferents. Journal of Comparative Neurology, 264, 396408.Google Scholar
Jakob, H. & Beckman, H. (1986) Prenatal developmental disturbances in the limbic allocortex in schizophrenics. Journal of Neural Transmission, 65, 303326.Google Scholar
Jellinger, K. (1985) Neuromorphological background of pathochemical studies in major psychoses. In Pathochemical Markers in Major Psychoses (eds H. Beckman & P. Reiderer), pp. 123. Heidelberg: Springer.Google Scholar
Jeste, D. & Lohr, J. B. (1989) Hippocampal pathologic findings in schizophrenia. A morphometric study. 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., Macmillan, J. F. & Crow, T. J. (1987) The occurrence of organic disease of possible or probable aetiological significance in a population of 268 cases of first episode schizophrenia. Psychological Medicine, 17, 371379.Google Scholar
Johnstone, E. C., Cooling, N. J., Frith, C. D., et al (1988) Phenomenology of organic and functional psychoses and the overlap between them. British Journal of Psychiatry, 153, 770776.Google Scholar
Kaufman, W. E. & Galaburda, A. M. (1989) Cerebrocortical microdysgenesis in neurologically normal subjects: a histopathologic study. Neurology, 39, 238244.CrossRefGoogle Scholar
Koop, M., Rilling, G., Hermann, A., et al (1986) Volumetric development of the fetal telencephalon, cerebral cortex, diencephalon and rhombencephalon including the cerebellum in man. Bibliotheca Anatomica, 28, 5378.Google Scholar
Kovelman, J. A. & Scheibel, A. B. (1984) A neurohistological correlate of schizophrenia. Biological Psychiatry, 191, 16011621.Google Scholar
Kraepelin, E. (1919) Dementia Praecox and Paraphrenia. Edinburgh: Livingston. (Transl. (1971) R. M. Barclay & G. M. Robertson. New York: R. E. Krieger.)Google Scholar
Kretschman, H-J., Kammradt, G., Krauthause, I. et al (1986) Growth of the hippocampal formation in man. Bibliotheca Anatomica, 28, 2752.Google Scholar
Kurihara, M., Yamashita, S., Miyake, S., et al (1986) Computed tomography of epileptic children: an investigation of the temporal horn. No To Hattatsu, 18, 452458.Google Scholar
Lander, E. S. (1988) Splitting schizophrenia. Nature, 336, 105106.Google Scholar
Larroche, J. C. (1984) Malformations of the nervous system. In Greenfields Neuropathology, 4th edn. (eds J. M. Adams, J. A. N. Corsellis & L. W. Duchen), p. 385. London: Edward Arnold.Google Scholar
Lemke, R. (1935) Untersuchungen uber die soziale Prognose der Schizophrenia unter besonderer Beruckichtigung des encephalographischen Befundes. Archives für Psychiatrie und Nervenkrankheiter, 104, 89135.CrossRefGoogle Scholar
Lewis, M. S. (1989a) Age incidence and schizophrenia: Part I. The season of birth controversy. Schizophrenia Bulletin, 15, 5973.Google Scholar
Lewis, M. S. (1989b) Age incidence and schizophrenia: Part II. Beyond age incidence. Schizophrenia Bulletin, 15, 7580.Google Scholar
Lewis, S. W. (1989) Congenital risk factors for schizophrenia. Psychological Medicine, 19, 513.Google Scholar
Lewis, S. W. & Murray, R. M. (1987) Obstetric complications, neurodevelopmental deviance and risk of schizophrenics. Journal of Psychiatric Research, 21, 413421.CrossRefGoogle Scholar
McConnell, S. K. (1988) Development and decision making in the mammalian cerebral cortex. Brain Research Reviews, 13, 123.Google Scholar
McGuffin, P., Farmer, A. & Gottesman, I. I. (1987a) Is there really a split in schizophrenia? The genetic evidence. British Journal of Psychiatry, 150, 581592.CrossRefGoogle ScholarPubMed
McGuffin, P., Murray, R. M. & Reveley, A. M. (1987b) Genetic influence on the psychoses. British Medical Bulletin, 43, 531536.Google Scholar
Mullan, M. J. & Murray, R. M. (1989) The impact of molecular genetics on our understanding of psychoses. British Journal of Psychiatry, 154, 591595.CrossRefGoogle ScholarPubMed
Murray, R. M., Lewis, S. W. & Reveley, A. M. (1985) Towards an aetilogical classification of schizophrenia. Lancet, i, 10231026.CrossRefGoogle Scholar
Murray, R. M., Lewis, S. W., Owen, M. J., et al (1988) The neurodevelopmental origins of dementia praecox. In Schizophrenia – The Major Issues (eds P. McGuffin & P. Bebbington), pp. 90107. London: Heinemann.Google Scholar
Murray, R. M. & Forester, A. (1987) Schizophrenia: is the concept disintegrating? Journal of Psychopharmacology, 1, 133139.Google Scholar
Nimgaonkar, V. L., Wessely, S. & Murray, R. M. (1988) Prevalence of familiality, obstetric complications and structural brain damage in schizophrenic patients. British Journal of Psychiatry, 153, 191197.Google Scholar
Nowakowski, R. S. (1987) Basic concepts of CNS development. Child Development, 58, 568595.Google Scholar
O'Callaghan, E., Larkin, C., Remond, O., et al (1988) ‘Early onset schizophrenia’ after teenage head injury. A case report with magnetic resonance imaging. British Journal of Psychiatry, 153, 394396.Google Scholar
Owen, M. J., Lewis, S. & Murray, R. M. (1989) Family history and cerebral ventricular enlargement in schizophrenia. A case control study. British Journal of Psychiatry, 154, 629634.CrossRefGoogle ScholarPubMed
Pakkenberg, B. (1987) Post-mortem study of chronic schizophrenic brains. British Journal of Psychiatry, 151, 744752.Google Scholar
Rakic, P. (1988) Specification of cerebral cortical areas. Science, 241, 170176.Google Scholar
Reveley, A. M., Chitkara, B. & Lewis, S. W. (1988) Ventricular and cranial size in schizophrenia: a 4–7 year follow-up. Schizophrenia Research, 1, 163.Google Scholar
Reynolds, G. P. (1989) Beyond the dopamine hypothesis: the neurochemical pathology of schizophrenia. British Journal of Psychiatry, 155, 305316.Google Scholar
Roberts, G. W. (1988) Abnormalities in brain structure in schizophrenia. Current Opinion in Psychiatry, 1, 8389.Google Scholar
Roberts, G. W. (1990) Brain development and CCK systems in schizophrenia: a working hypothesis. In International Perspectives in Schizophrenia Research (ed. M. Weller), pp. 5169. London: John Libbey.Google Scholar
Roberts, G. W., Colter, N., Lofthouse, R., et al (1986) Gliosis in schizophrenia. Biological Psychiatry, 21, 10431050.CrossRefGoogle ScholarPubMed
Roberts, G. W. & Crow, T. J. (1987) The neuropathology of schizophrenia - a progress report. British Medical Bulletin, 43, 599615.CrossRefGoogle ScholarPubMed
Roberts, G. W., Colter, N., Lofthouse, R. M., et al (1987) Is there gliosis in schizophrenia? Investigation of the temporal lobe. Biological Psychiatry, 22, 14591486.Google Scholar
Roberts, G. W. & Bruton, C. J. (1990) Notes from the graveyard: schizophrenia and neuropathology. Neuropathology and Applied Neurobiology, 16, 316.Google Scholar
Roberts, G. W., Done, D. J., Bruton, C. J., et al (1990) A ‘mock-up’ of schizophrenia. Schizophrenia-like psychoses and temporal lobe epilepsy. Biological Psychiatry, 28, 127143.Google Scholar
Robertson, M. (1989) False start on manic depression. Nature, 342, 222.Google Scholar
Schneider, G. E. (1979) Is it really better to have your brain lesion early? A revision of the ‘Kennard Principle’. Neuropsychologia. 17, 537583.Google Scholar
Shelton, R. C. & Weinberger, D. R. (1986) X-ray computerised tomography studies of schizophrenia: a review and synthesis. In The Neurology of Schizophrenia (eds H. A. Nasrallah & D. R. Weinberger). Amsterdam: Elsevier.Google Scholar
Stevens, J. R. (1982) Neuropathology of schizophrenia. Archives of General Psychiatry, 39, 11311139.CrossRefGoogle ScholarPubMed
Suddath, R. L., Casanoca, 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
Van Hoesen, G. W. (1982) The parahippocampal gyrus: its cortical connections in the monkey. Trends in Neurosciences, 5, 345350.Google Scholar
Volpe, J. J. (1989) Intraventricular hemorrhage in the premature infant – current concept. Part I. Annals of Neurology, 25, 311.Google Scholar
Vita, A., Sacchetti, E., Valvassori, G., et al (1988) Brain morphology in schizophrenia: a 2–5 year CT scan follow-up study. Acta Psychiatrica Scandinavica, 78, 618621.CrossRefGoogle Scholar
Weinberger, D. R. (1984) Computed tomography (CT) findings in schizophrenia: speculations on the meaning of it all. Journal of Psychiatric Research, 18, 477490.Google Scholar
Weinberger, D. R. (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Archives of General Psychiatry, 44, 660669.Google Scholar
Weinberger, D. R. (1988) Premorbid neuropathology in schizophrenia. Lancet, ii, 959960.Google Scholar
Woody, R. C., Bolyard, K., Eisenhauer, G., et al (1987) CT scan and MRI findings in a child with schizophrenia. Journal of Child Neurology, 2, 105110.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.