Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-23T21:44:35.008Z Has data issue: false hasContentIssue false

The Continuum of Psychosis and Its Genetic Origins

The Sixty-fifth Maudsley Lecture

Published online by Cambridge University Press:  02 January 2018

T. J. Crow*
Affiliation:
Division of Psychiatry, Clinical Research Centre, Watford Road, Harrow, Middlesex HA1 3UJ

Abstract

Attempts to draw a line of genetic demarcation between schizophrenic and affective illnesses have failed. It must be assumed that these diseases are genetically related. A post-mortem study has demonstrated that enlargement of the temporal horn of the lateral ventricle in schizophrenia but not in Alzheimer-type dementia is selective to the left side of the brain. This suggests that the gene for psychosis is the ‘cerebral dominance gene‘, the factor that determines the asymmetrical development of the human brain. That the psychosis gene is located in the pseudoautosomal region of the sex chromosomes is consistent with observations that sibling pairs with schizophrenia are more often than would be expected of the same sex and share alleles of a polymorphic marker at the short-arm telomeres of the X and Y chromosomes above chance expectation. That the cerebral dominance gene also is pseudoautosomal is suggested by the pattern of verbal and performance deficits associated with sex-chromosome aneuploidies. The psychoses may thus represent aberrations of a late evolutionary development underlying the recent and rapid increase in brain weight in the transition from Australopithecus through Homo habilis and Homo erectus to Homo sapiens.

Type
Lecture
Copyright
Copyright © Royal College of Psychiatrists, 1990 

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

Angst, J. & Scharfetter, C. (1990a) Familial aspects of bipolar schizoaffective disorder. In Affective Disorders, World Psychiatric Association Symposium, Athens, 1985, abstract S104. WPA.Google Scholar
Angst, J. & Scharfetter, C. (1990b) Schizoaffective Psychosen. Ein Nosologisches Aergernis. In Affektive Psychosen (eds E. Lungershausen, W. P. Kaschka & R. J. Witkowski). Stuttgart: Schattauer Verlag.Google Scholar
Angst, J. & Stassen, H. H. (1983) Classification of schizo-affective patients by multidimensional scaling and cluster analysis. Psychiatria Clinica, 16, 254264.Google Scholar
Annett, M. (1985) Left, Right, Hand and Brain: the Right Shift Theory. London: L. Erlbaum.Google Scholar
Book, J. A. (1953) Schizophrenia as a gene mutation. Acta Genetica et Statistica Medica, 4, 133139.Google ScholarPubMed
Broca, P. (1861) Perte de la parole. Ramollisement chronique et destruction partielle du lobe anterieur gauche du cerveau. Bulletin de la Society d'Anthropologie 2, 219235.Google Scholar
Brown, R., Colter, N., Corsellis, J. A. N., et al (1986) Post-mortem evidence of structural brain changes in schizophrenia. Archives of General Psychiatry, 43, 3642.CrossRefGoogle Scholar
Buhrich, N., Crow, T. J., Johnstone, E. C., et al (1988) Age disorientation in chronic schizophrenia is not associated with premorbid intellectual impairment or past physical treatment. British Journal of Psychiatry, 152, 466469.Google Scholar
Burgoyne, P. S. (1982) Genetic homology and crossing-over in the X and Y chromosomes of mammals. Human Genetics, 61, 8590.CrossRefGoogle ScholarPubMed
Collinge, J., Boccio, A., DeLisi, L. E., et al (1989) Evidence for a pseudoautosomal locus for schizophrenia: a sibling pair analysis. Cytogenetics and Cell Genetics, 51, 978.Google Scholar
Cooke, H. J., Brown, W. R. A. & Rappold, G. A. (1985) Hypervariable telomeric sequences from the human sex chromosomes are pseudoautosomal. Nature, 317, 687692.Google Scholar
Crichton-Browne, J. (1879) On the weight of the brain and its component parts in the insane. Brain, 2, 4267.Google Scholar
Crow, T. J. (1986a) Temporal disorientation in chronic schizophrenia: the implications of an “organic” psychological impairment for the concept of “functional” psychosis. In Contemporary Issues in Schizophrenia (eds A. Kerr & P. Snaith), pp. 168174. London: Gaskell.Google Scholar
Crow, T. J. (1986b) Secular changes in affective disorder and variations in the psychosis gene. Archives of General Psychiatry, 43, 10131014.Google Scholar
Crow, T. J. (1986c) The continuum of psychosis and its implication for the structure of the gene. British Journal of Psychiatry, 149, 419429.Google Scholar
Crow, T. J. (1987) Pseudoautosomal locus for psychosis? Lancet, ii, 1532.CrossRefGoogle Scholar
Crow, T. J. (1988) Sex chromosomes and psychosis: the case for a pseudoautosomal locus. British Journal of Psychiatry, 153, 675683.Google Scholar
Crow, T. J. (1989) Pseudoautosomal locus for the cerebral dominance gene. Lancet, ii, 339340.Google Scholar
Crow, T. J. & Mitchell, W. S. (1975) Subjective age in chronic schizophrenia: evidence for a sub-group of patients with defective learning capacity? British Journal of Psychiatry, 126, 360363.CrossRefGoogle ScholarPubMed
Crow, T. J. & Stevens, M. (1978) Age disorientation in chronic schizophrenia: the nature of the cognitive deficit. British Journal of Psychiatry, 133, 137142.Google Scholar
Crow, T. J., Ball, J., Bloom, S. R., et al (1989a) Schizophrenia as an anomaly of development of cerebral asymmetry. Archives of General Psychiatry, 46, 11451150.CrossRefGoogle ScholarPubMed
Crow, T. J., DeLisi, L. E., & Johnstone, E. C. (1989b) Concordance by sex in sibling pairs with schizophrenia is paternally inherited: evidence for a pseudoautosomal locus. British Journal of Psychiatry, 155, 9297.CrossRefGoogle ScholarPubMed
Crow, T. J., DeLisi, L. E. & Johnstone, E. C. (1990) In reply … a locus closer to the telomere? British Journal of Psychiatry, 156, 416420.Google Scholar
Curtis, D. & Gurling, H. (1990) Unsound methodology in investigating a pseudoautosomal locus in schizophrenia. British Journal of Psychiatry, 156, 415416.Google Scholar
Dax, M. (1865) Lesions de la moitié gauche de l'éncéphale coincident avec l'oublie des signes de la pensée. Lu à congres meridionel ténu à Montpellier en 1836. Gazette Hebdomadal de Medecin et Chirurgie, 11, 259260.Google Scholar
Decina, P., Luscas, L. R., Linder, J. R., et al (1989) Parent–child pairs with major psychiatric diseases. 142nd meeting of the American Psychiatric Association, San Francisco, May 1989, abstract no. 105. Washington, DC: APA.Google Scholar
Egeland, J. A., Gerhard, D. S., Pauls, D. L., et al (1987) Bipolar affective disorders linked to DNA markers on chromosome 11. Nature, 325, 783787.CrossRefGoogle ScholarPubMed
Essen-Moller, E. (1955) The calculation of morbid risk in parents of index cases, as applied to a family sample of schizophrenics. Acta Genetica, 5, 334342.Google Scholar
Ferguson-Smith, M. A. (1965) Karyotype–phenotype correlations in gonadal dysgenesis and their bearing on the pathogenesis of malformations. Journal of Medical Genetics, 2, 142155.Google Scholar
Forssman, H. (1970) The mental implications of sex chromosome aberrations. British Journal of Psychiatry, 117, 353363.Google Scholar
Gershon, E. S., DeLisi, L. E., Hamovit, J., et al (1988) A controlled family study of chronic psychoses: schizophrenia and schizo-affective disorder. Archives of General Psychiatry, 45, 328336.Google Scholar
Gershon, E. S., Hamovit, J., Guroff, J. J., et al (1982) A family study of schizoaffective, bipolar I, bipolar II, unipolar and normal control patients. Archives of General Psychiatry, 39, 11571167.CrossRefGoogle Scholar
Geschwind, N. & Levitsky, W. (1968) Left-right asymmetry in temporal speech region. Science, 161, 186187.Google Scholar
Goodfellow, P. J., Darling, S. M., Thomas, N. S., et al (1986) A pseudoautosomal gene in man. Science, 234, 740743.Google Scholar
Heaton-Ward, A. (1977) Psychosis in mental handicap. British Journal of Psychiatry, 130, 525533.CrossRefGoogle ScholarPubMed
Jamison, K. R. (1990) Manic-depressive illness and accomplishment: creativity, leadership, and social class. In Manic-Depressive Illness (eds F. K. Goodwin & K. R. Jamison), p. 999. Oxford: Oxford University Press (in press).Google Scholar
Jerison, H. J. (1973) Evolution of the Brain and Intelligence. New York: Academic Press.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
Kallman, F. J. (1946) The genetic theory of schizophrenia: an analysis of 691 schizophrenic twin index families. American Journal of Psychiatry, 103, 309322.Google Scholar
Karlsson, J. L. (1984) Creative intelligence in relatives of mental patients. Hereditas, 100, 8386.Google Scholar
Kelsoe, J. R., Ginns, E. I., Egeland, J. A., et al (1989) Re-evaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish. Nature, 342, 238243.CrossRefGoogle ScholarPubMed
Kendell, R. E. & Gourlay, J. (1970) The clinical distinction between the affective psychoses and schizophrenia. British Journal of Psychiatry, 117, 261266.Google Scholar
Klerman, G. L., Lavori, P. W., Rice, J., et al (1985) Birth-cohort trends in rates of major depressive disorder among relatives of patients with affective disorder. Archives of General Psychiatry, 42, 689693.Google Scholar
Roller, P. C. & Darlington, C. D. (1934) The genetical and mechanical properties of the sex chromosomes. I. Rattus Norvegicus. Journal of Genetics, 29, 159173.Google Scholar
Kraepelin, E. (1920) Der Erscheinungsformen der Irreseins. Zeitschrift fur Gesammte Neurologie u Psychiatrie 62, 129.Google Scholar
Kraepelin, E. (1919) Dementia Praecox and Paraphrenia (trans. Barclay, R. M.). New York: R. E. Krieger.Google Scholar
Kringlen, E. (1968) Heredity and Environment in the Functional Psychoses: An Epidemiological-Clinical Twin Study. London: Heinemann.Google Scholar
Lane, E. A. & Albee, G. W. (1964) Early childhood intellectual differences between schizophrenic adults and their siblings. Journal of Abnormal and Social Psychology, 68, 193195.Google Scholar
Lancet (1987) A continuum of psychosis? Lancet, ii, 889890.Google Scholar
Levy, J. (1977) The mammalian brain and the adaptive advantage of cerebral asymmetry. Annals of the New York Academy of Sciences, 299, 264272.Google Scholar
Lewis, A. J. (1958) Fertility and mental illness. Eugenics Review, 50, 91106.Google Scholar
Liddle, P. & Crow, T. J. (1984) Age disorientation in chronic schizophrenia is associated with global intellectual impairment. British Journal of Psychiatry, 144, 193199.Google Scholar
McManus, I. C. (1985) Handedness, language dominance and aphasia: a genetic model. Psychological Medicine, (suppl. 8), 140.Google Scholar
Maier, W., Hallmeyer, J. & Heun, R. (1989) A controlled family study in affective and schizophrenic disorders: support for continuum models and spectrum concepts. 1st World Congress of Psychiatric Genetics Abstracts, 1, 35.Google Scholar
Mott, F. W. (1910) Hereditary aspects of nervous and mental disease. British Medical Journal, ii, 10131020.Google Scholar
Netley, C. T. (1986) Summary overview of behavioural development in individuals with neonatally identified X and Y aneuploidy. Birth Defects, 22, 293306.Google Scholar
Netley, C. T. & Rovet, J. (1987) Relations between dermatoglyphic measure, hemispheric specialization, and intellectual abilities in 47, XXY males. Brain and Cognition, 6, 153160.Google Scholar
Netley, C. T., Rovet, J. (1982) Atypical hemispheric lateralization in Turner syndrome subjects. Cortex, 18, 377384.Google Scholar
Odegaard, O. (1972) The multifactorial inheritance of predisposition to schizophrenia. In Genetic Factors in “Schizophrenia” (ed. A. R. Kaplan), pp. 256275. Springfield, Illinois: Thomas.Google Scholar
Offord, D. R. & Cross, L. A. (1971) Adult schizophrenia with scholastic failure or low IQ in childhood. Archives of General Psychiatry, 24, 431436.Google Scholar
Penrose, L. S. (1942) Auxiliary genes for determining sex as contributory causes of mental illness. Journal of Mental Science, 88, 308316.Google Scholar
Penrose, L. S. (1945) Survey of cases of familial mental illness. Mimeographed document prepared for the Ontario Department of Health. Abstracted in Digest of Neurology and Psychiatry, 13, 644.Google Scholar
Penrose, L. S. (1968) Critical survey of schizophrenia genetics. In Modern Perspectives in World Psychiatry (ed. J. G. Howells), pp. 319. Edinburgh: Oliver & Boyd.Google Scholar
Pilbeam, D. & Gould, S. J. (1974) Size and scaling in human evolution. Science, 186, 892901.Google Scholar
Pollock, H. M. & Malzberg, B. (1940) Hereditary and environmental factors in the causation of manic-depressive psychosis and dementia praecox. American Journal of Psychiatry, 96, 12271247.Google Scholar
Powell, A., Thomson, N., Hall, D. J., et al (1973) Parent–child concordance with respect to sex and diagnosis in schizophrenia and manic-depressive psychosis. British Journal of Psychiatry, 123, 653658.Google Scholar
Price, R. A., Kidd, K. K., Pauls, D. L., et al (1985) Multiple threshold models for affective disorders: the Yale-NIMH collaborative family study. Journal of Psychiatric Research, 19, 533546.CrossRefGoogle ScholarPubMed
Reynolds, G. P. (1983) Increased concentration and lateral asymmetry of amygdala dopamine in schizophrenia. Nature, 305, 527529.Google Scholar
Rice, J., Reich, T., Andreasen, N., et al (1987) The familial transmission of bipolar illness. Archives of General Psychiatry, 44, 441447.Google Scholar
Rosanoff, A. J., Handy, L. M., Plesset, I. R., et al (1934) The etiology of so-called schizophrenic psychoses. American Journal of Psychiatry, 91, 247286.Google Scholar
Rosenthal, D. (1962) Familial concordance by sex with respect to schizophrenia. Psychological Bulletin, 59, 401421.Google Scholar
Rosenthal, D. (1970) Genetic Theory and Abnormal Behavior. New York: McGraw-Hill.Google Scholar
Slater, E. T. O. (1936) Inheritance of manic-depressive insanity. Lancet, i, 429431.Google Scholar
Slater, E. T. O. (1953) Sex-linked recessives in mental illness? Acta Genetica et Statistica Medica, 4, 273280.Google Scholar
Stassen, H. H., Scharfetter, C., Winokur, G., et al (1988) Familial syndrome patterns in schizophrenia, schizoaffective disorder, mania, and depression. European Archives of Psychiatry and Neurological Sciences, 237, 115123.Google Scholar
Sturt, E. & Shur, E. (1985) Sex concordance for schizophrenia in proband-relative pairs. British Journal of Psychiatry, 147, 4447.Google Scholar
Weissenbach, J., Levilliers, J., Petit, C., et al (1987) Normal and abnormal interchanges between the human X and Y chromosomes. Development (suppl.) 108, 6774.Google Scholar
Zerbin-Rudin, E. (1972) Genetic research and the theory of schizophrenia. International Journal of Mental Health, 1, 4262.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.