Hostname: page-component-78c5997874-94fs2 Total loading time: 0 Render date: 2024-11-17T19:53:33.550Z Has data issue: false hasContentIssue false

Sex Chromosomes and Psychosis

The Case for a Pseudoautosomal Locus

Published online by Cambridge University Press:  02 January 2018

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

Abstract

Although the incidence of the recurrent psychoses (bipolar affective illness and schizophrenia) in the two sexes is approximately equal, gender influences a number of aspects of major psychiatric disease: unipolar depressive illness is twice as common in females, onset of schizophrenia is earlier and outcome is worse in males, and pairs of psychotic first-degree relatives are more often than expected of the same sex. In addition, sex chromosomal aneuploidies (e.g. XXY and XXX) are more frequent in patients with psychosis. Some of these findings can be explained if there is a major locus of predisposition to psychiatric disease in the ‘pseudoautosomal’ region of the sex chromosomes – that distal segment of the short arms in which there is genetic exchange between X and Y chromosomes at male meiosis. A gene located here would be transmitted in an autosomal manner, but would be passed above chance expectation to children of the same sex when inherited through a male. In that this segment of the sex chromosomes is subject to a high rate of recombination (which could generate new mutations), and may include determinants of brain lateralisation, it appears that the pseudoautosomal region could carry the genes which predispose to the major psychoses.

Type
Point of View
Copyright
Copyright © Royal College of Psychiatrists, 1988 

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

Abdullah, S., Jarvik, L. F., Kato, T., Johnston, W. C. & Lanzkron, J. (1969) Extra Y chromosome and its psychiatric implications. Archives of General Psychiatry, 21, 497501.CrossRefGoogle Scholar
Akesson, H. O. (1983) Psychiatric Disorders in Males with Supernumerary X Chromosomes. Goteborg: University of Goteborg.Google Scholar
Anders, J. M., Jagiello, G., Polani, P. E., Gianelli, F., Hamerton, J. L. & Leiberman, D. M. (1968) Chromosome findings in chronic psychotic patients. British Journal of Psychiatry, 114, 11671174.CrossRefGoogle ScholarPubMed
Annett, M. (1985) Left, Right, Hand and Brain: the Right Shift Theory. London: Erlbaum.Google Scholar
Asaka, A., Tsuboi, T., Inouye, E., Nagumo, Y., Hamada, S. & Okada, K. (1967) Schizophrenic psychosis in triple-X females. Folia Psychiatrica et Neurologica Japonica, 21, 271281.Google Scholar
Axelsson, R. & Wahlstrom, J. (1984) Chromosome aberrations in patients with paranoid psychosis. Hereditas, 100, 2931.CrossRefGoogle ScholarPubMed
Baker, D., Telfer, M. A., Richardson, C. E. & Clark, G. R. (1970) Chromosome errors in men with antisocial behavior. Journal of the American Medical Association, 5, 869878.Google Scholar
Burgoyne, P. S. (1982) Genetic homology and crossing-over in the X and Y chromosomes of mammals. Human Genetics, 61, 8590.Google Scholar
Casey, M. D., Segal, L. J., Street, D. R. K. & Blank, C. E. (1966) Sex chromosome abnormalities in two state hospitals for patients requiring special security. Nature, 209, 641642.CrossRefGoogle ScholarPubMed
Cowie, V., Coppen, A. & Norman, P. (1960) Nuclear sex and body build in schizophrenia. British Medical Journal, ii, 431433.CrossRefGoogle Scholar
Crow, T. J. (1983) Is schizophrenia an infectious disease? The Lancet, i, 173175.Google Scholar
Crow, T. J. (1984) A re-evaluation of the viral hypothesis: is psychosis the result of retroviral integration at a site close to the cerebral dominance gene? British Journal of Psychiatry, 145, 243253.CrossRefGoogle Scholar
Crow, T. J. (1986) The continuum of psychosis and its implication for the structure of the gene. British Journal of Psychiatry, 149, 419429.Google Scholar
Crow, T. J. (1987a) Mutation and psychosis: a suggested explanation of seasonality of birth. Psychological Medicine, 17, 821828.Google Scholar
Crow, T. J. (1987b) Pseudoautosomal locus for psychosis? The Lancet, ii, 1532.Google Scholar
Darwin, C. (1871) The Descent of Man, and Selection in Relation to Sex, Vol. II. Reprinted 1981. New Jersey: Princeton.Google Scholar
Dasgupta, J., Dasgupta, G. & Balasubrahmanyan, M. (1973) XXY syndrome, XY/XO mosaicism and acentric chromosomal fragments in male schizophrenics. Indian Journal of Medical Research, 61, 6270.Google ScholarPubMed
DeLisi, L. E., White, B., Reiss, A. & Gershon, E. S. (1986). Cytogenetic studies of schizophrenic patients. In Biological Psychiatry 1985 (eds Shagass, C. et al), pp. 6466. New York: Elsevier Science.Google Scholar
Faber, P. & Abrams, R. (1975) Schizophrenia in a 47,XYY male. British Journal of Psychiatry, 127, 401403.Google Scholar
Gershon, E. S., Targum, S. D., Matthysse, S. & Bunney, W. E. (1979) Color blindness not closely linked to bipolar illness. Archives of General Psychiatry, 36, 14231430.Google Scholar
Gershon, E. S., Hamovit, J., Guroff, J. J., Dibble, E., Leckmann, J. F., Sceery, W., Targum, S. D., Nurnberger, J. I., Goldin, L. R. & Bunney, W. E. (1982) A family study of schizo-affective, bipolar I, bipolar II, unipolar and normal control probands. Archives of General Psychiatry, 39, 11571167.Google Scholar
Geschwind, N. & Levitsky, W. (1968) Left-right asymmetry in temporal speech region. Science, 161, 186187.Google Scholar
Goetzl, U., Green, R., Whybrow, P. & Jackson, R. (1974) X linkage revisited; a further study of manic–depressive illness. Archives of General Psychiatry, 31, 665672.Google Scholar
Goodfellow, P. J., Darling, S., Banting, G., Pym, B., Mondello, C. & Goodfellow, P. N. (1987) Pseudoautosomal genes in man. Development, 101 (suppl.), 119125.Google Scholar
Goodwin, F. K. & Jamison, K. (1984) The natural course of manic–depressive illness. In Neurobiology of Mood Disorders (eds Post, R. M. & Ballenger, J. C.), pp. 2037. Baltimore: Williams & Wilkins.Google Scholar
Gottesman, I. I. & Shields, J. (1982) Schizophrenia: The Epigenetic Puzzle, pp. 8586. Cambridge: Cambridge University Press.Google Scholar
Haverkamp, F., Propping, P. & Hilger, T. (1982) Is there an increase in reproductive rates in schizophrenia? Critical review of the literature. Archiv fur Psychiatrie und Nervenkrankheiten, 232, 439450.Google Scholar
James, N. McI. & Chapman, C. J. (1975) A genetic study of bipolar affective illness. British Journal of Psychiatry, 126, 449456.Google Scholar
Johnson, G. F. S. & Leeman, M. M. (1977) Analysis of familial factors in bipolar affective illness. Archives of General Psychiatry, 34, 10741083.Google Scholar
Judd, L. L. & Brandkamp, W. W. (1967) Chromosome analyses of adult schizophrenics. Archives of General Psychiatry, 16, 316324.Google Scholar
Kaplan, A. R. (1972) Chromosomal aneuploidy, genetic mosaicism, occasional acentric fragments, and schizophrenia: association of schizophrenia with rare cytogenetic anomalies. In Genetic Factors in “Schizophrenia” (ed. Kaplan, A. R.), pp. 351373. Springfield: Thomas.Google Scholar
Karlsson, J. L. (1974) Inheritance of schizophrenia. Acta Psychiatrica Scandinavica (suppl. 247).Google Scholar
Kidd, C. B., Knox, R. S. & Mantle, D. J. (1963) A psychiatric investigation of triplc-X chromosome females. British Journal of Psychiatry, 109, 9094.Google Scholar
Koller, P. C. & Darlington, C. D. (1934) The genetical and mechanical properties of the sex chromosomes I. Rattus norvegicus. Journal of Genetics, 29, 159173.CrossRefGoogle Scholar
Macciardi, F., Provenza, M., Bellodi, L. & Smeraldi, E. (1987) Genetic notes of schizophrenic disorders. In Etiopathogenetic Hypotheses of Schizophrenia (eds Cazzullo, C. L., Invernizzi, G., Sacchetti, E. & Vita, A.), pp. 2132. Lancaster: MTP Press.Google Scholar
Maclean, N., Court Brown, W. M., Jacobs, P. A., Mantle, D. J. & Strong, J. A. (1968) A survey of sex chromatin abnormalities in mental hospitals. Journal of Medical Genetics, 5, 165172.CrossRefGoogle ScholarPubMed
Malzberg, B. (1935) A statistical study of age in relation to mental disease. Mental Hygiene, 19, 449476.Google Scholar
McKeever, W. F. & Hoff, A. L. (1982) Familial sinistrality, sex, and laterality differences in naming and lexical decision latencies of right-handers. Brain and Language, 17, 225239.Google Scholar
McManus, I. C. (1985) Handedness, language dominance and aphasia: a genetic model. Psychological Medicine (suppl. 8), 140.CrossRefGoogle Scholar
Melnyk, J. & Derencsenyi, A. (1969) XYY survey in an institution for sex offenders and the mentally ill. Nature, 224, 369370.CrossRefGoogle Scholar
Mendlewicz, J. & Rainer, J. D. (1974) Morbidity risk and genetic transmission in manic depressive illness. American Journal of Human Genetics, 26, 692701.Google Scholar
Money, J. (1963) Cytogenetic and psychosexual incongruities with a note on space-form blindness. American Journal of Psychiatry, 119, 820827.Google Scholar
Money, J. & Hirsch, S. R. (1963) Chromosome anomalies, mental deficiency, and schizophrenia. Archives of General Psychiatry, 8, 242251.CrossRefGoogle Scholar
Muller, N. & Endres, M. (1987) An XX male with schizophrenia: a case of personality development and illness similar to that in XXY males. Journal of Clinical Psychiatry, 48, 379380.Google Scholar
Nielsen, J. (1975) Chromosome examination of male patients in a psychiatric hospital. British Journal of Psychiatry, 127, 404409.Google Scholar
Nielsen, J., Christensen, A.-L., Johnsen, S. G. & Froland, A. (1966) Psychopathology and testis histology in a patient with the XYY syndrome. Acta Medico Scandinavica, 180, 747757.CrossRefGoogle Scholar
Olanders, S. (1975) Females with Supernumerary X Chromosomes. Goteborg: University of Goteborg.Google Scholar
Olsson, B. & Rett, A. (1986) Shift to right handedness in Rett syndrome around age 7. American Journal of Medical Genetics, 24, 133141.Google Scholar
Page, D. C., Brown, L. G. & de la Chapelle, A. (1987) Exchange of terminal portions of X- and Y-chromosomal short arms in human XX males. Nature, 328, 437440.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 (mimeo-graphed report abstracted). Digest of Neurology and Psychiatry, 13, 644.Google Scholar
Perris, C. (1968) Genetic transmission of depressive psychoses. Acta Psychiatrica Scandinavica, Suppl. 203, 4552.Google Scholar
Polani, P. E. (1982) Pairing of X and Y chromosomes, non-inactivation of X-linked genes, and the maleness factor. Human Genetics, 60, 207211.Google Scholar
Price, W. H., Strong, J. A., Whatmore, P. B. & McClemont, W. F. (1966) Criminal patients with XYY sex-chromosome complement. The Lancet, i, 565566.Google Scholar
Raphael, T. & Shaw, M. W. (1963) Chromosome studies in schizophrenia. Journal of the American Medical Association, 183, 10221028.Google Scholar
Ratcliffe, S. G., Murray, L. & Teague, P. (1986) Edinburgh study of growth and development of children with sex chromosome abnormalities III. Birth Defects, 22, 73118.Google ScholarPubMed
Reed, S. C., Hartley, C., Anderson, V. E., Phillips, V. P. & Johnson, N. A. (1973) The Psychoses: Family Studies. Philadelphia: Saunders.Google Scholar
Reich, T., Clayton, P. & Winokur, G. (1969) Family history studies: V The genetics of mania. American Journal of Psychiatry, 125, 13581369.Google Scholar
Rice, J., Reich, T., Andreasen, N. C., Endicott, J., Van Eerdewegh, M., Fishman, R., Hirschfeld, R. M. A. & Klerman, G. L. (1987) The familial transmission of bipolar illness. Archives of General Psychiatry, 44, 441447.Google Scholar
Risch, N., Baron, M. & Mendlewicz, J. (1986) Assessing the role of X-linked inheritance in bipolar-related major affective illness. Journal of Psychiatric Research, 20, 275288.Google Scholar
Rosenthal, D. (1962) Familial concordance by sex with respect to schizophrenia. Psychological Bulletin, 59, 401421.Google Scholar
Rosenthal, D. (1966) The offspring of schizophrenic couples. Journal of Psychiatric Research, 4, 169188.CrossRefGoogle ScholarPubMed
Rouyer, F., Simmler, M.-C., Johnsson, C., Vergnaud, G., Cooke, H. J. & Weissenbach, J. (1986) A gradient of sex linkage in the pseudoautosomal region of the human sex chromosomes. Nature, 319, 291295.Google Scholar
Sartorius, N., Jablensky, A., Korten, A., Ernberg, G., Anker, M., Cooper, J. E. & Day, R. (1986) Early manifestations and first-contact incidence of schizophrenia in different cultures. Psychological Medicine, 16, 909928.Google Scholar
Schulz, B. (1932) Zur Erbpathologie der Schizophrenie. Zeitschrift fur die Gesammte Neurologie und Psychiatrie, 143, 175293.Google Scholar
Shimizu, A., Kurachi, M., Yamaguchi, N., Torii, H. & Isaki, K. (1987) Morbidity risk of schizophrenia to parents and siblings of schizophrenic patients. Japanese Journal of Psychiatry and Neurology, 41, 6570.Google ScholarPubMed
Slater, E. T. O. (1953) Sex-linked recessives in mental illness? Acta Genetica et Statistica Medico, 4, 273280.Google Scholar
Slater, E. T. O. & Zilkha, K. (1961) A case of Turner mosaic with myopathy and schizophrenia. Proceedings of the Royal Society of Medicine, 54, 674675.Google Scholar
Sperber, M. A., Salomon, L., Collins, M. H. & Stambler, M. (1972) Childhood schizophrenia and 47,XXY Klinefelter's syndrome. American Journal of Psychiatry, 128, 14001408.Google Scholar
Tedeschi, L. G. & Freeman, H. (1962) Sex chromosomes in male schizophrenics. Archives of General Psychiatry, 6, 109111.CrossRefGoogle ScholarPubMed
Trixler, M., Kosztolanyi, G. & Mehes, K. (1976) Sex chromosome aberration screening among male psychiatric patients. Archiv fur Psychiatrie und Nervenkrankheiten, 221, 273282.Google Scholar
Tsuang, M. T. (1967) A study of pairs of sibs both hospitalised for mental disorder. British Journal of Psychiatry, 113, 283300.Google Scholar
van Eerdewegh, M. M., Gershon, E. S. & van Eerdewegh, P. M. (1980) X-chromosome threshold models of bipolar manic–depressive illness. Journal of Psychiatric Research, 15, 215238.Google Scholar
Vartanian, M. E. & Gindilis, V. M. (1972) The role of chromosomal aberrations in the clinical polymorphism of schizophrenia. International Journal of Mental Health, 1, 93106.CrossRefGoogle Scholar
Wahlstrom, J. & Anvret, M. (1986) Chromosome findings in the Rett syndrome and a test of a two-step mutation theory. American Journal of Medical Genetics, 24, 361368.Google Scholar
Weissenbach, J., Levilliers, J., Petit, C., Rouyer, F. & Simmler, M.-C. (1987) Normal and abnormal interchanges between the human X and Y chromosomes. Development, 101 (suppl.), 6774.Google Scholar
Winokur, G., Clayton, P. J. & Reich, T. (1969) Manic–Depressive Illness. St Louis: C. V. Mosby.Google Scholar
Zehnder, M. (1941) Uber Krankheitsbild und Krankheitsverlauf bei schizophrenen Geschwistern. Monatschrift fur Psychiatrie und Neurologie, 103, 231277.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.