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A Re-Evaluation of the Viral Hypothesis: Is Psychosis the Result of Retroviral Integration at a Site Close to the Cerebral Dominance Gene?

Published online by Cambridge University Press:  29 January 2018

Timothy J. Crow
Timothy J. Crow*
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex HA1 3UJ
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Summary

The extent to which concordance rates for schizophrenia in monozygotic twins (between 36 and 58%) fall short of 100% is often taken as an index of the role of an environmental factor in schizophrenia, but such an agent remains elusive. That schizophrenic symptoms are observed in some viral illnesses suggests that schizophrenia might be due to a gene-virus interaction, but analysis of age of onset in pairs of siblings with the disease rules out horizontal transmission. An alternative hypothesis is proposed that onset of disease is due to the expression of a ‘provirus', which is integrated in the genome, having been acquired either by prenatal infection or in the germ-line from an affected parent; this could explain why the season of birth effect is accentuated in, and perhaps confined to the group of patients without a family history of the disease.

Germ-line integration is known to occur following infection with agents of the retrovirus class.∗ Such agents can integrate at many sites in the host genome, but their interactions with proto-oncogenes (cellular genes which may act as growth factors) identify one type of integration site, and are. associated with some of their pathogenic effects. Some characteristics of schizophrenic illness, particularly their selectivity for the dominant hemisphere, can be understood on the assumption that the virus (perhaps a retrovirus) responsible for the disease interacts with a proto-oncogene, which induces the asymmetrical brain growth responsible, for laterality and cerebral dominance. The aetiologies of manic-depressive illness and schizophrenia may be related (the season of birth and onset effects are the same for the two conditions) and there is some evidence that the former transmutes into the latter in succeeding generations. The persistence of the functional psychoses may be due to the ability of the psychosis gene (or ‘provirus’) to induce change in the genetic mechanisms responsible for the development of laterality. (∗ See postscript pp 253).

Type
Research Article
Information
The British Journal of Psychiatry , Volume 145 , Issue 3 , September 1984 , pp. 243 - 253
Copyright
Copyright © 1984 The Royal College of Psychiatrists 

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References

Abe, K. (1969) The morbidity rate and environmental influence in monozygotic co-twins of schizophrenics. British Journal of Psychiatry, 115, 519–31.CrossRefGoogle ScholarPubMed
Adam, J., Crow, T. J., Duchen, L. W., Scaravilli, F. & Spokes, E. (1982) Familial cerebral amyloidosis and spongiform encephalopathy. Journal of Neurology, Neurosurgery & Psychiatry, 45, 37–45.CrossRefGoogle ScholarPubMed
Albrecht, P., Torrey, E. F., Boone, E., Hicks, J. T. & Daniel, N. (1980) Raised cytomegalovirus-antibody level in cerebrospinal fluid of schizophrenic patients. Lancet, 2, 769–72.Google ScholarPubMed
Annett, M. (1978) A Single Gene Explanation of Right and Left Handedness and Brainedness. Coventry: Lancaster Polytechnic.Google Scholar
Annett, M. (1981) The genetics of handedness. Trends in Neurosciences, 4, 256–8.Google Scholar
Asher, D. M., Kaufman, C. A., Kleinman, J. E., Weinberger, D. R., Gibbs, C. J. & Gajdusek, D. C. (1984) Attempts to transmit schizophrenia to animals. Proceedings of the 137th Annual Meeting of the American Psychiatric Association, Los Angeles 5–11th May.Google Scholar
Baillarger, L. (1857) Example de contagion d'un delire monomanique. La Moniteur des Hospitaux, 45, 353–4.Google Scholar
Baker, H. F., Bloxham, C. A., Crow, T. J., Davies, H., Ferrier, I. N., Johnstone, E. C., Parry, R. P., Ridley, R. M., Taylor, G. R. & Tyrrell, D. A. J. (1983) The viral hypothesis: some experimental approaches. Advances in Biological Psychiatry, 12, 1–19.Google Scholar
Baltimore, D. (1970) RNA-dependent DNA polymerase in virions of RNA tumor viruses. Nature, 226, 1209–11.CrossRefGoogle Scholar
Bentvelzen, P. & Daams, J. H. (1969) Hereditary infections with mammary tumor viruses in mice. Journal of the National Cancer Institute, 43, 1025–35.Google Scholar
Benveniste, R. E. & Todaro, G. J. (1974) Evolution of C-type viral genes: inheritance of exogenously acquired viral genes. Nature, 252, 456–9.CrossRefGoogle ScholarPubMed
Bishop, J. M. (1983) Cancer genes come of age. Cell, 32, 1018–20.Google ScholarPubMed
Boklage, C. E. (1977) Schizophrenia, brain asymmetry development and twinning: cellular relationship with etiological and possibly prognostic implications. Biological Psychiatry, 12, 19–35.Google ScholarPubMed
Böök, J. A. (1953) A genetic and neuropsychiatric investigation of a North Swedish population. Acta genetica et statistica Medica, 4, 1–100.Google ScholarPubMed
Brown, R., Colter, N., Corsellis, J. A. N., Crow, T. J., Frith, C. D., Jagoe, R., Johnstone, E. C. & Marsh, L. (1984) Changes in Brain Weight and Structure in the Functional Psychoses (in preparation).Google Scholar
Bryant, R. C. (1983) Genetics of schizophrenia. Lancet, i, 1158–9.Google Scholar
Crocetti, G. M., Kulcar, Z., Kesic, B. & Lemkau, P. V. (1971) Selected aspects of the epidemiology of psychoses in Croatia, Yugoslavia. III The cluster sample and results of the pilot survey. American Journal of Epidemiology, 94, 126–34.Google Scholar
Crow, T. J. (1981) Biological basis of mental disorders: the case for viral aetiology. In Epidemiological Impact of Psychotropic Drugs, edited by Tognoni, G., Bellantuono, C. and Lader, M. H. Amsterdam: Elsevier/N. Holland.Google Scholar
Crow, T. J. (1983a) Is schizophrenia an infectious disease? Lancet, i, 173–5.Google Scholar
Crow, T. J. (1983a) Schizophrenia as an infection. Lancet, i, 819–20.Google Scholar
Crow, T. J. (1984) Integrated viral genes as the cause of schizophrenia: a hypothesis. Proceedings of the Tenth Annual Conference of the British Association of Psychopharmacology, Guernsey, April 4th to 8th. Oxford: Oxford University Press.Google Scholar
Crow, T. J. & Done, D. J. (1984) Age of onset of schizophrenia in siblings. (In preparation).Google Scholar
Crow, T. J. Ferrier, I. N., Johnstone, E. C., MacMillan, J. F., Owens, D. G. C., Parry, R. P. & Tyrrell, D. A. J. (1979) Characteristics of patients with schizophrenia or neurological disorder and viruslike agent in cerebrospinal fluid. Lancet, i, 842–4.Google Scholar
Dale, P. W. (1981) Prevalence of schizophrenia in the Pacific Islands of Micronesia. Journal of Psychiatric Research, 16, 103–11.Google Scholar
Fischer, M. (1973) Genetic and environmental factors in schizophrenia. Acta Psychiatrica Scandinavica, 238, 1–58.Google Scholar
Flor-Henry, P. (1969) Psychosis and temporal lobe elilepsy: a controlled investigation. Epilepsia, 10, 363–95.Google Scholar
Galaburda, A. M., Le May, M., Kemper, T. L. & Geschwind, N. (1978) Right-left asymmetries in the brain. Science, 199, 852–6.CrossRefGoogle ScholarPubMed
Goodall, E. (1927) The Eighth Maudsley Lecture: Dealing with some of the work done to elucidate the pathology of the disease falling to be considered under the rubric “insanity”. Journal of Mental Science, 73, 363–90.Google Scholar
Goodall, E. (1932) The exciting cause of certain states, at present classified under “schizophrenia” by psychiatrists, may be infection. Journal of Mental Science, 78, 746–55.Google Scholar
Gottesman, I. I. (1978) Schizophrenia and genetics: Where are we? Are you sure? In: The Nature of Schizophrenia, edited by Wynne, L. C., Cromwell, R. L. & Matthysse, S. New York: Wiley.Google Scholar
Hare, E. H. & Moran, P. (1980) A relation between seasonal temperature and the birth rate of schizophrenic patients. Acta Psychiatrica Scandinavica, 63, 396–405.Google Scholar
Hare, E. H. (1983a) Was insanity on the increase? British Journal of Psychiatry, 142, 439–55.CrossRefGoogle ScholarPubMed
Hare, E. H. (1983b) Epidemiological evidence for a viral factor in the aetiology of the functional psychoses. Advances in Biological Psychiatry, 12, 52–75.Google Scholar
Hare, E. H. & Walter, S. D. (1978) Seasonal variation in admissions of psychiatric patients and its relation to seasonal variation in their birth. Journal of Epidemiology and Community Health, 32, 47–52.CrossRefGoogle Scholar
Harper, P. S. (1977) Mendelian inheritance or transmissible agent?—the lessons of Kuru and Australia antigen. Journal of Medical Genetics, 14, 389–98.CrossRefGoogle ScholarPubMed
Hendrick, I. (1928) Encephalitis lethargica and the interpretation of mental disease. American Journal of Psychiatry, 84, 898–1014.Google Scholar
Himmelhoch, J., Pincus, J., Tucker, G. & Detre, T. (1970) Subacute encephalitis: behavioural and neurological aspects. British Journal of Psychiatry, 116, 531–8.CrossRefGoogle ScholarPubMed
Hirsch, S. R. (1983) Cytomegalic inclusion virus in schizophrenia c.s.f. Proceedings of VIIth World Congress of Psychiatry, Vienna, June 1983.Google Scholar
Hofbauer, B. (1864) Infectio psychica. Osterreichische Medicinische Wochenschrift, 39.Google Scholar
Hunter, R. & Jones, M. (1966) Acute lethargica-type encephalitis. Lancet, 2, 1023–4.Google Scholar
Jaenisch, R. (1976) Germ line integration and Mendelian transmission of the exogenous Moloney leukemia virus. Proceedings of the National Academy of Science, 73, 1260–4.CrossRefGoogle ScholarPubMed
Jelliffe, S. E. (1927) The mental pictures in schizophrenia and in epidemic encephalitis. American Journal of Psychiatry, 6, 413–65.Google Scholar
Karlsson, J. L. (1970a) The rate of schizophrenia in foster-reared close relatives of schizophrenic index cases. Biological Psychiatry, 2, 285–90.Google Scholar
Karlsson, J. L. (1970b) Genetic association of giftedness and creativity with schizophrenia. Hereditas, 66, 177–81.Google Scholar
Kasanetz, E. F. (1979) Tecnica per investigare il ruolo di fattori ambientale sulla genesi delia schizofrenia. Rivista di Psicologia Analitica, 10, 193–202.Google Scholar
Kelleher, M. J., Copeland, J. R. M. & Smith, A. J. (1974) High first admission rates for schizophrenia in the West of Ireland. Psychological Medicine, 4, 460–2.CrossRefGoogle ScholarPubMed
Kendell, R. E. & Gourlay, J. (1970) The clinical distinction between the affective psychoses and schizophrenia. British Journal of Psychiatry, 117, 261–6.Google ScholarPubMed
King, D. J., Cooper, S. J., Martin, S. M. et al (1984) A survey of serum antibodies to eight common viruses in psychiatric patients. British Journal of Psychiatry (in press).Google Scholar
Kinney, D. K. & Jacobsen, B. (1978) Environmental factors in schizophrenia: New adoption study evidence in The Nature of Schizophrenia. Edited by: Wynne, L. C., Cromwell, R. & Mattlysse, S. New York: Wiley.Google Scholar
Levy, J. (1969) Possible basis for the evolution of lateral specialisation of the human brain. Nature, 224, 614–5.Google Scholar
Lewis, R. M. (1974) Spontaneous auto-immune diseases of domestic animals. International Revue of Experimental Pathology, 13, 55–82.Google Scholar
Lindsay, J., Ounsted, C. & Richards, P. (1979) Long-term outcome in children with temporal lobe seizures. III Psychiatric aspects in childhood and adult life. Developmental Medicine and Childhood Neurology, 21, 630–6.Google ScholarPubMed
Lipton, H. L., Friedmann, A., Sethi, P. & Crowther, J. B. (1983) Characterisation of Vilyuisk virus as a Picornavirus. Journal of Medical Virology, 12, 195–203.Google Scholar
Lloyd Still, R. M. (1958) Psychosis following Asian influenza in Barbados. Lancet, 2, 21–1.Google Scholar
Luchins, D., Pollin, W. & Wyatt, R. J. (1980) Laterality in monozygotic schizophrenic twins: an alternative hypothesis. Biological Psychiatry, 15, 87–93.Google Scholar
Luchins, D. Weinberger, D. R. & Wyatt, R. J. (1979) Anomalous lateralisation associated with a milder form of schizophrenia. American Journal of Psychiatry, 136, 1598–99.Google Scholar
Lwoff, A. (1965) Interaction among virus, cell and organism. In Nobel Lectures in Physiology or Medicine 1963–1970. Amsterdam: Elsevier.Google Scholar
McCowan, P. K. & Cook, L. C. (1928) The mental aspect of chronic epidemic encephalitis. Lancet, i, 1316.CrossRefGoogle Scholar
Menninger, K. A. (1928) The schizophrenic syndrome as a product of acute infectious disease. Archives of Neurology & Psychiatry, 20, 464–81.CrossRefGoogle Scholar
Menninger, K. A. (1926) Influenza and schizophenia. An analysis of post-influenzal “dementia praecox” as of 1918, and five years later. American Journal of Psychiatry, 5, 469–529.CrossRefGoogle Scholar
Miller, E. (1971) Handedness and the pattern of human ability. British Journal of Psychology, 62, 111–2.Google Scholar
Misra, P. C. & Hay, G. G. (1971) Encephalitis presenting as acute schizophrenia. British Medical Journal, 1, 523–33.CrossRefGoogle ScholarPubMed
Murray, R. M. & Reveley, A. M. (1983a) Schizophrenia as an infection. Lancet, i, 583.Google Scholar
Murray, R. M. & Reveley, A. M. (1983b) Genetics of schizophrenia. Lancet, i, 1159–60.Google Scholar
Myerson, A. (1925) The Inheritance of Mental Diseases. Baltimore: Williams and Wilkins.Google Scholar
Narayan, O., Herzog, S., Frese, K., Scheefers, H. & Roft, R. (1983) Behavioural disease in rats caused by immunopathological responses to persistent borna virus in the brain. Science, 220, 1401–2.Google Scholar
Payne, L. N. & Chubb, R. C. (1968) Studies on the nature and genetic control of an antigen in normal chick embryos which reacts in the COFAL test. Journal of General Virology, 3, 379–91.CrossRefGoogle ScholarPubMed
Penrose, L. S. (1942) Auxiliary genes for determining sex as contributory causes of mental illness. Journal of Mental Science, 88, 308–16.Google Scholar
Petursson, G., Martin, J. R., Georgsson, N., Nathanson, N. & Palsson, P. A. (1979) Visna, the biology of the agent and the disease. In Aspects of Slow and Persistent Virus Infections, edited by Tyrrell, D. A. J. The Hague: Martinus Nijhoff.Google Scholar
Pollin, W. & Stabenau, J. R. (1968) Biological, psychological and historical differences in a series of monozygotic twins discordant for schizophrenia. Journal of Psychiatric Research, 6, 317–32.CrossRefGoogle Scholar
Powell, A., Thomson, N., Hall, D. J. & Wilson, L. (1973) Parent-child concordance with respect to sex and diagnosis in schizophrenia and manic-depressive psychosis. British Journal of Psychiatry, 123, 653–8.Google Scholar
Ravenholt, R. T. & Foege, W. H. (1982) 1918 Influenza, Encephalitis Lethargica, Parkinsonism. Lancet, 2, 860–4.Google Scholar
Reynolds, G. P. (1983) Increased concentrations and lateral asymmetry of amygdala dopamine in schizophrenia. Nature, 305, 527–9.Google Scholar
Rosenthal, D. (1962) Familial concordance by sex with respect to schizophrenia. Psychological Bulletin, 59, 401–21.Google Scholar
Rosenthal, D. (1970) Genetic Theory and Abnormal Behaviour. New York: McGraw-Hill.Google Scholar
Sackheim, H. A. & Decina, P. (1983) Lateralised neuropsychological abnormalities in bipolar adults and in children of bipolar probands. In Laterality and Psychopathology, edited by FlorHenry, P. and Gruzelier, J. Amsterdam: Elsevier.Google Scholar
Scharfetter, C. (1970) On the hereditary aspects of symbiontic psychoses. A contribution towards the understanding of the schizophrenia-like psychoses. Psychiatric Clinics, 3, 145–52.Google Scholar
Schulz, B. (1940) Erkrandungsalter schizophrenen Eltern und Kinder. Zeitschrift fur Neurologie und Psychiatrie, 168, 709–21.Google Scholar
Sobin, A. & Ozer, M. N. (1966) Mental disorders in acute encephalitis. Journal of the Mount Sinai Hospital, 33, 73–82.Google Scholar
Taylor, D. C. (1975) Factors influencing the occurrence of schizophrenia-like psychosis in patients with temporal lobe epilepsy. Psychological Medicine, 5, 249–54.Google Scholar
Taylor, G. R., Crow, T. J., Ferrier, I. N., Johnstone, E. C., Parry, R. P. & Tyrrell, D. A. J. (1982) Virus-like agent in schizophrenia and some neurological disorders. Lancet, 2, 1166–7.Google Scholar
Taylor, P. J., Dalton, R., Fleminger, J. J. & Lishman, W. A. (1982) Differences between two studies of hand preference in psychiatric patients. British Journal of Psychiatry, 140, 166–73.Google Scholar
Temin, H. M. (1980) Origin of retroviruses from cellular moveable genetic elements. Cell, 21, 599–600.Google Scholar
Temin, H. M. & Mizutani, S. (1970) RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature, 226, 1211–3.Google Scholar
Torrey, E. F. (1980) Schizophrenia and Civilisation. New York: Jason Aronson.Google Scholar
Torrey, E. F. McGuire, M., O'Hare, A., Walsh, D. & Spellman, M. P. (1984) Endemic psychosis in Western Ireland. American Journal of Psychiatry (in press).Google Scholar
Torrey, E. F., Torrey, B. B. & Petersen, M. R. (1977) Seasonality of schizophrenic births in the United States. Archives of General Psychiatry, 34, 1065–70.Google Scholar
Torrey, E. F., Torrey, B. B. & Burton-Bradley, B. G. (1974) The epidemiology of schizophrenia in Papua-New Guinea. American Journal of Psychiatry, 131, 567–73.Google Scholar
Torrey, E. F. Yolken, R. H. & Winfrey, C. J. (1982) Cytomegalovirus antibody in cerebrospinal fluid of schizophrenic patients detected by enzyme immunoassay. Science, 216, 892–4.Google Scholar
Torrey, E. F. Yolken, R. H. & Albrecht, A. (1983) Cytomegalovirus as a possible etiological agent in schizophrenia. Advances in Biological Psychiatry, 12, 150–60.Google Scholar
Tyrrell, D. A. J., Parry, R. P., Crow, T. J., Johnstone, E. C. & Ferrier, I. N. (1979) Possible virus in schizophrenia and some neurological disorders. Lancet, i, 839–41.Google Scholar
Walker, S. F. (1980) Lateralisation of functions in the vertebrate brain: a review. British Journal of Psychiatry, 71, 329–367.Google Scholar
Watson, C. G., Kucala, T., Tilleskjor, C. & Jacobs, L. (1984) Schizophrenic birth seasonality in relation to the incidence of infectious diseases and temperature extremes. Archives of General Psychiatry, 41, 85–90.Google Scholar
Weinstein, E. A. Linn, L. & Kahn, R. L. (1955) Encephalitis with a clinical picture of schizophrenia. Journal of the Mount Sinai Hospital, 21, 341–54.Google Scholar
Weiss, R. A. (1978) Why cell biologists should be aware of genetically transmitted viruses. National Cancer Institute Monograph, 48, 183–9.Google Scholar
Wollenberg, R. (1889) Ueber psychische infection. Archiv für Psychiatrie, 20, 62–88.CrossRefGoogle Scholar
Wunderlich, V. & Zotter, S. (1982) Abrogation of infectivity of mouse mammary tumor virus by reserpine. Experimental Pathology, 21, 59–61.Google Scholar
Wunderlich, V. Fey, F. & Sydow, G. (1980) Antiviral effect of haloperidol on Rauscher murine leukemia virus. Archiv Geschwultsforschung, 50, 758–62.Google Scholar
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