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The Genetics of Schizophrenia is the Genetics of Neurodevelopment

Published online by Cambridge University Press:  02 January 2018

Peter Jones  and
Robin M. Murray
Peter Jones*
Affiliation:
Genetics Section, Department of Psychological Medicine, Institute of Psychiatry and King's College Hospital
Robin M. Murray
Affiliation:
Institute of Psychiatry and King's College Hospital, London
*
∗Genetics Section, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF
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Extract

Genes are now accepted as being important in the aetiology of schizophrenia (Gottesman & Shields, 1982; McGuffin et al, 1987), and over the past decade the emphasis in genetic research has shifted away from genetic epidemiology to searching the chromosomal DNA for the genes themselves. Despite this increasing technical sophistication, the application of linkage analysis to families multiply affected by schizophrenia has been accompanied by the familiar controversy over the exact borders of the adult clinical phenotype (Sherrington et al, 1988; St Clair et al, 1989). Indeed, the preoccupation of researchers with the vagaries of the clinical definition has resulted in repeated attempts to use genetic studies to determine the relative validity of different operational definitions of schizophrenia (McGuffin et al, 1984; Farmer et al, 1987). To us, such studies beg the question of how precisely genes are involved in the aetiology of schizophrenia; after all, genes code for proteins, not for auditory hallucinations in the third person.

Type
Molecular Biology Symposium
Information
The British Journal of Psychiatry , Volume 158 , Issue 5 , May 1991 , pp. 615 - 623
Copyright
Copyright © Royal College of Psychiatrists, 1991 

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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, 1094–1098.Google Scholar
Benes, F. M. (1989) Myelination of cortical-hippocampal relays during late adolescence. Schizophrenia Bulletin, 15, 585–593.CrossRefGoogle ScholarPubMed
Benes, F. M., Davidson, J. & Bird, E. D. (1986) Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics. Archives of General Psychiatry, 43, 31–35.CrossRefGoogle ScholarPubMed
Benes, F. M. & Bird, E. D. (1987) An analysis of the arrangement of neurones in the cingulate cortex of schizophrenic patients. Archives of General Psychiatry, 44, 608–616.Google Scholar
Blackshaw, S. & Bowen, R. C. (1987) A case of atypical psychosis associated with alexithymia and left fronto-temporal lesion. Canadian Journal of Psychiatry, 32, 668–692.CrossRefGoogle ScholarPubMed
Blinkov, S. M. & Glezer, I. I. (1968) The Human Brain in Figures and Tables: A Quantitative Handbook. New York: Plenum.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, 784–791.CrossRefGoogle ScholarPubMed
Bogerts, B., Ashtari, M., Degreef, G., et al (1990a) Reduced temporal limbic structure volumes on magnetic resonance images in first episode schizophrenia. Psychiatry Research, Neuroimaging, 35, 1–13.CrossRefGoogle ScholarPubMed
Bogerts, B., Falkai, P., Haupts, M., et al (1990b) Postmortem volume measurements of limbic systems and basal ganglia structures in chronic schizophrenics. Initial results from a new brain collection. Schizophrenia Research, 3, 295–301.CrossRefGoogle ScholarPubMed
Brown, A. W. & Brierley, J. B. (1973) The earliest alterations in rat neurons and astrocytes after anoxia-ischaemia. Acta Neuropathologica (Berlin), 23, 9–22.Google Scholar
Bruton, C. J., Crow, T. J., Frith, C. D., et al (1990) Schizophrenia and the brain. Psychological Medicine, 20, 285–304.Google Scholar
Cannon, T. D., Mednick, S. A. & Parnas, J. (1989) Genetic and perinatal determinants of structural brain deficits in schizophrenia. Archives of General Psychiatry, 46, 883–889.Google Scholar
Caviness, V. S. & Rakic, P. (1978) Mechanisms of cortical development. A view from mutations in mice. Annual Review of Neuroscience, 1, 297–326.CrossRefGoogle ScholarPubMed
Chavrier, P., Zerial, M., Lemaire, P., et al (1988) A gene encoding a protein with zinc fingers is activated during GO/G1 transition in cultured cells. EMBO Journal, 7, 29–35.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, 1027–1032.Google Scholar
Cohen, J., Burne, J. F., McKinlay, C., et al (1987) The role of laminin and the laminin/fibronectin receptor complex in the outgrowth of retinal ganglion cell axons. Developmental Biology, 122, 407–418.CrossRefGoogle ScholarPubMed
Conrad, A. J. & Scheibel, A. B. (1987) Schizophrenia and the hippocampus. The embryological hypothesis extended. Schizophrenia Bulletin, 13, 577–587.Google Scholar
Cowan, W. M., Fawcett, J. W., O'Leary, D. D., et al (1984) Regressive events in neurogenesis. Science, 225, 1258–1265.Google Scholar
Crossin, K. L. (1989) Cell and substrate adhesion molecules in embryonic and neural development. Clinical Chemistry, 35, 738–747.Google Scholar
Deakin, J. F. W., Slater, P., Simpson, M. D. C., et al (1989) Frontal cortical and left temporal glutamatergic dysfunction in schizophrenia. Journal of Neurochemistry, 52, 1781–1786.Google Scholar
DeLisi, L. E., Hoff, A. L., Schwartz, J., et al (1990) Brain morphology at the onset of schizophrenics. Proceedings of the American Psychiatric Association, Annual Meeting, New York. Washington, DC: APA.Google Scholar
Eagles, J. M., Gibson, I., Bremner, M. H., et al (1990) Obstetric complications in DSM–III schizophrenics and their siblings. Lancet, 334, 1139–1141.CrossRefGoogle Scholar
Eckenhoff, M. F. & Rakic, P. (1984) Radial organisation of the hippocampal dentate gyrus. A golgi, ultrastructural and immunocytochemical analysis in the developing rhesus monkey. Journal of Comparative Neurology, 223, 1–21.CrossRefGoogle ScholarPubMed
Edelman, G. M. (1986) Cell adhesion molecules in the regulation of animal form and tissue pattern. Annual Review of Cell Biology, 2, 81–116.CrossRefGoogle ScholarPubMed
Edelman, G. M. (1988) Morphoregulatory molecules. Biochemistry, 27, 3533–3543.Google Scholar
Edelman, G. M. & Chuong, C. M. (1982) Embryonic to adult conversion of neural cell adhesion molecules in normal and staggerer mice. Proceedings of the National Academy of Sciences, USA, 79, 7036–7040.CrossRefGoogle ScholarPubMed
Edmondson, J. C. & Hatten, M. E. (1987) Glial-guided granule neuron migration in vitro: a high-resolution time-lapse video microscopic study. Journal of Neuroscience, 7, 1928–1934.CrossRefGoogle ScholarPubMed
Edmondson, J. C., Liem, R. K., Kuster, J. E., et al (1988) Astrotactin: a novel neuronal cell surface antigen that mediates neuron–astroglial interactions in cerebellar microcultures. Journal of Cell Biology, 106, 505–517.Google Scholar
Falkai, P. & Bogerts, B. (1986) Cell loss in the hippocampus of schizophrenics. European Archives of Psychiatry and Neurological Science, 236, 154–161.CrossRefGoogle ScholarPubMed
Falkai, P, Bogerts, B & Rozumek, M. (1988) Limbic pathology in schizophrenia. The entorhinal region - a morphometric study. Biological Psychiatry, 24, 515–521.Google Scholar
Farmer, A. E., McGuffin, P. & Gottesman, I. I. (1987) Twin concordance for DSM–III schizophrenia. Archives of General Psychiatry, 44, 634–641.CrossRefGoogle ScholarPubMed
Ghysen, A. & Dambly-Chaudiere, C. (1989) Genesis of the Drosophila peripheral nervous system. Trends in Genetics, 5, 251–255.CrossRefGoogle ScholarPubMed
Goodman, R. (1988) Are complications of pregnancy and birth causes of schizophrenia? Developmental Medicine and Child Neurology, 30, 391–395.Google Scholar
Goodman, R. (1989) Neuronal misconnections and psychiatric disorder. Is there a link? British Journal of Psychiatry, 154, 292–299.CrossRefGoogle ScholarPubMed
Gottesman, I. I. & Shields, J. (1982) Schizophrenia – The Epigenetic Puzzle. Cambridge: Cambridge University Press.Google Scholar
Green, M. F., Satz, P., Soper, H. V., et al (1987) Relationship between physical anomalies and age of onset of schizophrenia. American Journal of Psychiatry, 144, 666–669.Google ScholarPubMed
Greenberg, J. M., Boehm, T., Sofronieuw, M. V., et al (1990) Segmental and developmental regulation of a presumptive T-cell oncogene in the central nervous system. Nature, 344, 158–160.Google Scholar
Greenough, W. T., Black, J. E. & Wallace, C. S. (1987) Experience and brain development. Child Development, 58, 539–559.CrossRefGoogle ScholarPubMed
Gualtieri, C. T., Adams, A. & Shen, C. D. (1982) Minor physical anomalies in alcoholic and schizophrenic adults and hyperactive and autistic children. American Journal of Psychiatry, 139, 640–643.Google ScholarPubMed
Guy, J. D., Majorski, L. V., Wallace, C. J., et al (1983) The incidence of minor physical anomalies in adult male schizophrenics. Schizophrenia Bulletin, 9, 571–582.CrossRefGoogle ScholarPubMed
Hatten, M. E. (1990) Riding the glial monorail: a common mechanism for glial-guided neuronal migration in different regions of the developing mammalian brain. Trends in Neuroscience, 13, 179–184.Google Scholar
Hatten, M. E., Liem, R. K. H. & Mason, C. A. (1984) Two forms of cerebellar glial cells interact differently with neurons in vitro. Journal of Cell Biology, 98, 193–204.CrossRefGoogle ScholarPubMed
Hatten, M. E., Liem, R. K. H. & Mason, C. A. (1986) Weaver mouse cerebellar granule neurons fail to migrate on wild-type astroglial processes in vitro. Journal of Neuroscience, 6, 2676–2683.Google Scholar
He, X., Treacy, M. N., Simmons, D. M., et al (1989) Expression of a large family of POU-domain regulatory genes in mammalian brain development. Nature, 340, 35–42.Google Scholar
Henderson, C. E., Benoit, P., Huchet, M. et al (1986) Increase of neurite-promoting activity for spinal neurons in muscles of ‘paralyse’ mice and tenotomised rats. Brain Research, 390, 65–70.Google Scholar
Herndon, R. M., Margolis, G. & Kilham, L. (1971) The synaptic organisation of the malformed cerebellum induced by perinatal infection with feline panleukopenia virus (PLV):1. Elements forming the cerebellar glomeruli. Journal of Neuropathology and Experimental Neurology, 30, 196–205.Google Scholar
Hickey, T. L. & Hitchcock, P. F. (1984) Genesis of neurons in the dorsal lateral geniculate nucleus of the cat. Journal of Comparative Neurology, 228, 186–199.Google Scholar
Hubel, D. H. & Wiesel, T. N. (1970) The period of susceptibility to the physiological effects of unilateral eye closure in kittens. Journal of Physiology, 206, 419–436.Google Scholar
Jakob, H. & Beckman, H. (1986) Prenatal developmental disturbances in the limbic allocortex in schizophrenics. Journal of Neural Transmission, 65, 303–326.Google Scholar
Jeste, D. V. & Lohr, J. B. (1989) Hippocampal pathologic findings in schizophrenia: a morphometric study. Archives of General Psychiatry, 46, 1019–1024.Google Scholar
Jorgensen, B. J. & Diemer, N. H. (1982) Selective neuron loss after cerebral ischaemia in the rat: possible role of transmitter glutamate. Acta Neurologica Scandinavica, 66, 536–546.CrossRefGoogle ScholarPubMed
Kolb, B. (1989) Brain development, plasticity, and behaviour. American Psychologist, 44, 1203–1212.CrossRefGoogle Scholar
Kovelman, J. A. & Scheibel, A. B. (1984) A ncurohistological correlate of schizophrenia. Biological Psychiatry, 19, 1601–1621.Google Scholar
Kuffler, S. W., Nicholls, J. G. & Martin, A. R. (1984) From Neuron to Brain: A Cellular Approach to the Function of the Nervous System (2nd edn). Sunderland: Sinauer.Google Scholar
Lewis, S. W. (1987) A comparison of schizophrenics with and without intracranial abnormalities on CT. MPhil thesis, University of London.Google Scholar
Lewis, S. W. & Mezey, G. C. (1985) Clinical correlates of septum pellucidum cavities. Psychological Medicine, 15, 43–54.Google Scholar
Lewis, S. W. & Murray, R. M. (1987) Obstetric complications, neurodevelopmental deviance, and risk of schizophrenia. Journal of Psychiatric Research, 21, 413–421.CrossRefGoogle ScholarPubMed
Lewis, S. W., Owen, M. J. & Murray, R. M. (1989) Obstetric complications and schizophrenia; methodology and mechanisms. In Schizophrenia: A Scientific Focus (eds S. C. Schulz & C. A. Tamminga). New York: Oxford University Press.Google Scholar
Liesi, P. (1985) Laminin-immunoreactive glia distinguish regenerative adult CNS systems from non-regenerative ones. EMBO Journal, 4, 2505–2511.Google Scholar
Lindner, J., Rathjen, F. G. & Schachner, M. (1983) L1 mono-and polyclonal antibodies modify cell migration in early post natal mouse cerebellum. Nature, 305, 427–430.CrossRefGoogle Scholar
Lyons, F., Martin, M. L., Maguire, C., et al (1988) The expression on N-CAM serum fragment is positively correlated with severity of negative features in type II schizophrenia. Biological Psychiatry, 23, 769–775.Google Scholar
Matus, A. (1988) Microtubule-associated proteins and neuronal morphogenesis. In The Making of the Nervous System (eds J. G. Parnavelas, C. D. Stern & R. V. Stirling), pp. 421–433. Oxford: Oxford University Press.Google Scholar
McConnell, S. K. (1988) Fates of visual cortical neurons in the ferret after isochronic and heterochronic transplantation. Journal of Neuroscience, 18, 945–974.Google Scholar
McConville, C. M., Formstone, C. J., Hernandez, D., et al (1990) Fine mapping of the chromosome 11q 22–23 region using PFGE, linkage and haplotype analysis; localisation of the gene for ataxia telangiectasia to a 5cM region flanked by NCAM/DRD2 and STMY/CJ52.75, 0 2.22. Nuclear Acids Research, 18, 4335–4343.CrossRefGoogle Scholar
Mcguffin, P., Farmer, A. E., Gottesman, I. I., et al (1984) Twin concordance for operationally defined schizophrenia. Confirmation of familiality and heritability. Archives of General Psychiatry, 41, 541–545.Google Scholar
Mcguffin, P., Murray, R. M. & Reveley, A. M. (1987) Genetic influence on the psychoses. British Medical Bulletin, 43, 531–556.CrossRefGoogle ScholarPubMed
McNeil, T. F. (1987) Perinatal influences in the development of schizophrenia. In Biological Perspectives of Schizophrenia (eds H. Helmchen & F. A. Henn), pp. 125–138. Chichester: Wiley.Google Scholar
McNeil, T. F. & Kaij, L. (1978) Obstetric factors in the development of schizophrenia - complications in the births of preschizophrenics and in reproduction by schizophrenic parents. In The Nature of Schizophrenia (eds L. C. Wynne, R. L. Cromwell & S. Matthysize), pp. 401–429. New York: Wiley.Google Scholar
Mednick, S. A., Machon, R. A. & Huttunen, M. O. (1990) An update on the Helsinki influenza project. Archives of General Psychiatry, 47, 292.Google Scholar
Murray, B. A., Hemperly, J. J. Prediger, E. A., et al (1986) Alternatively spliced mRNAs code for different polypeptide chains of the chicken neural cells adhesion molecule (N-CAM). Journal of Cell Biology, 102, 189–193.Google Scholar
Murray, R. M., Lewis, S. & Reveley, A. M. (1985) Towards an aetiological classification of schizophrenia. Lancet, i, 1023–1026.Google Scholar
Murray, R. M., Jones, P. B. & O'Callaghan, E. (1990) Foetal brain development and later schizophrenia. In Proceedings of Ciba Symposium No. 156. The Childhood Environment and Adult Disease. Chichester: Wiley.Google Scholar
Nasrallah, H. A., Bogerts, B., Olson, S., et al (1990) Correlates of hippocampus hypoplasia schizophenia. In Proceedings of the American Psychiatric Association, Annual Meeting, New York. Washington, DC: APA.Google Scholar
Nornes, H. O. & Das, G. D. (1974) Temporal patterns of neurons in spinal cord of the rat: I. An autoradiographic study - time and sites of origin and migration and settling pattern of neuroblasts. Brain Research, 73, 121–138.CrossRefGoogle Scholar
Nowakowski, R. S. (1987) Basic concepts of CNS development. Child Development, 58, 568–595.CrossRefGoogle ScholarPubMed
Nowakowski, R. S. & Rakic, P. (1981) The site of origin and route of migration of neurons to the hippocampal region of the rhesus monkey. Journal of Comparative Neurology, 196, 129–154.Google Scholar
O'Callaghan, E., Larkin, C., Kinsella, A., et al (1990) Obstetric complications, the putative familial - sporadic distinction, and tardive dyskinesia in schizophrenia. British Journal of Psychiatry, 157, 578–584.CrossRefGoogle ScholarPubMed
O'Leary, D. D. & Stanfield, B. B. (1985) Occipital cortical neurons with transient pyramidal tract axons extend and maintain collaterals to subcortical but not intracortical targets. Brain Research, 336, 326–333.Google Scholar
Oppenheim, R. W. (1981) Cell death of motor neurons in the chick embryo spinal cord. V. Evidence on the role of cell death and neuromuscular function in the formation of specific connections. Journal of Neuroscience, 1, 141–151.Google Scholar
Owen, M. J., Lewis, S. W. & Murray, R. M. (1988) Obstetric complications and schizophrenia: a computed tomographic study. Psychological Medicine, 18, 331–339.CrossRefGoogle ScholarPubMed
Owen, M. J., Lewis, S. W. & Murray, R. M. (1989) Family history and cerebral ventricular enlargement in schizophrenia: a case control study. British Journal of Psychiatry, 154, 629–634.Google Scholar
Rakic, P. (1971) Neuronglia relationship during granule cell migration in developing cerebellar cortex: a golgi and electron microscopic study in macacus rhesus. Journal of Comparative Neurology, 141, 283–312.CrossRefGoogle ScholarPubMed
Rakic, P. (1988) Specification of cerebral cortical area. Science, 241, 170–176.Google Scholar
Rakic, P., Bourgeois, J. P., Eckenhoff, M. F., et al (1986) Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science, 232, 232–235.Google Scholar
Randall, P. L. (1983) Schizophrenia, abnormal connections and brain evolution. Medical Hypotheses, 10, 247–280.Google Scholar
Raper, J. A., Chang, S., Kapfhammer, J. P., et al (1988) Growth cone guidance and labelled axons. In The Making of the Nervous System (eds J. G. Parnavelas, C. D. Stern & R. V. Stirling), pp. 188–203. Oxford: Oxford University Press.Google Scholar
Reveley, A. M., Reveley, M. A., Clifford, C. A., et al (1982) Cerebral ventricular size in twins discordant for schizophrenia. Lancet, i, 540–541.Google Scholar
Reveley, A. M. & Reveley, M. A., (1983) Aqueduct stenosis and schizophrenia. Journal of Neurology, Neurosurgery and Psychiatry, 46, 18–22.Google Scholar
Risch, N. (1990) Linkage strategies for genetically complex traits. 1. Multilocus models. American Journal of Human Genetics, 46, 222–228.Google Scholar
Schugart, K., Utset, M. F., Fienberg, A., et al (1989) Homeobox containing genes: implications for pattern formation during embryonic development in the mouse. In Genetics of Neuropsychiatric Diseases (ed. L. Wetterberg). Basingstoke: Macmillan.Google Scholar
Sherrington, R., Brynjolfsson, J., Petursson, H., et al (1988) Localisation of a susceptibility locus for schizophrenia on chromosome 5. Nature, 336, 164–167.Google Scholar
Smith, D. W. (1976) Recognizable Patterns in Human Malformation: Genetic, Embryologic and Clinical Aspects. Philadelphia: Saunders.Google Scholar
St Clair, D., Blackwood, D., Muir, W., et al (1989) No linkage of chromosome 5q11-q13 markers to schizophrenia in Scottish families. Nature, 339, 305–309.Google Scholar
Stirling, R. V. & Summerbell, D. (1988) Motor axon guidance in the developing chick limb. In The Making of the Nervous System (eds J. G. Parnavelas, C. D. Stern & R. V. Stirling), pp. 228–247. Oxford: Oxford University Press.Google Scholar
Suddath, R. L., Christison, G., Torrey, E. F., et al (1989) Quantitative magnetic resonance imaging in twin pairs discordant for schizophrenia. Schizophrenia Research, 2, 129.Google Scholar
Suddath, R. L., Christison, G., Torrey, E. F., et al (1990) Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. New England Journal of Medicine, 322, 789–794.Google Scholar
Sutcliffe, J. G., Milner, R. J., Gottesfeld, J. M., et al (1984) Control of neuronal gene expression. Science, 225, 1308–1315.Google Scholar
Temple, S. & Raff, M. C. (1986) Clonal analysis of oligodendrocyte development in culture: evidence for a developmental clock that counts cell divisions. Cell, 44, 773–779.Google Scholar
Thanos, S., Bonhoeffer, F. & Rutishauser, U. (1984) Fiber-fiber interaction and tectal cues influence the development of the chicken retinotectal projection. Proceedings of the National Academy of Sciences, USA, 81, 1906–1910.Google Scholar
Trisler, D. & Collins, F. (1987) Corresponding spatial gradients of TOP molecules in the developing retina and optic tectum. Science, 237, 1208–1209.CrossRefGoogle ScholarPubMed
Waddington, J. L., O'Callaghan, E. & Larkin, C. (1990) Physical anomalies and neurodevelopmental abnormality in schizophrenia: new clinical correlates. Schizophrenia Research, 3, 90.Google Scholar
Weinberger, D. R. (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Archives of General Psychiatry, 44, 660–669.Google Scholar
Wetts, R. & Herrup, K. (1982) Cerebellar purkinje cells are descended from a small number of projenitors committed during early development: quantitative analysis of Lurcher chimeric mice. Journal of Neuroscience, 2, 1494–1498.CrossRefGoogle ScholarPubMed
Wiesel, T. N. (1982) Postnatal development of the visual cortex and the influence of environment. Nature, 299, 583–591.Google Scholar
Wilkinson, D. G., Bhatt, S., Cook, M., et al (1989a) Segmental expression of Hox-2 homobox-containing genes in the developing mouse hindbrain. Nature, 341, 405–409.Google Scholar
Wilkinson, D. G., Bhatt, S., Chavrier, P., et al (1989b) Segment specific expression of a zinc-finger gene in the developing nervous system of the mouse. Nature, 337, 461–464.Google Scholar
Yakovlev, P. I. & Lecours, A. R. (1967) The myelogenic cycles of regional maturation of the brain. In Regional Development of the Brain and Early Life (ed. A. Minowski), pp. 3–70. Boston: Blackwell Scientific.Google Scholar
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