Hostname: page-component-7c8c6479df-fqc5m Total loading time: 0 Render date: 2024-03-28T20:37:19.671Z Has data issue: false hasContentIssue false

Heterogeneity of Schizophrenia

Conceptual Models and Analytic Strategies

Published online by Cambridge University Press:  02 January 2018

Ming T. Tsuang*
Affiliation:
Section of Psychiatric Epidemiology and Genetics, Harvard Medical School Department of Psychiatry, Massachusetts Mental Health Center; Harvard Program in Psychiatric Epidemiology; Psychiatry Service, Brockton/West Roxbury Veterans Administration Medical Center
Michael J. Lyons
Affiliation:
Department of Psychology, Boston University; Section of Psychiatric Epidemiology and Genetics, Harvard Medical School Department of Psychiatry, Massachusetts Mental Health Center; Psychiatry Service, Brockton/West Roxbury Veterans Administration Medical Center
Stephen V. Faraone
Affiliation:
Section of Psychiatric Epidemiology and Genetics, Harvard Medical School Department of Psychiatry, Massachusetts Mental Health Center; Psychiatry Service, Brockton/West Roxbury Veterans Administration Medical Center
*
Brockton/West Roxbury Veterans Administration Medical Center, 940 Belmont Street, Brockton, Massachusetts, 02401, USA

Abstract

Schizophrenia is clinically heterogeneous but it is not known whether this is due to the existence of discrete subtypes. For the purpose of explication, ‘indicators' of schizophrenia are divided into three levels: phenomenology, pathophysiology, and aetiology. Five heterogeneity models and a number of quantitative approaches are described. It is imperative to apply rigorous methods of study to the comparison of unitary models and competing heterogeneity models of schizophrenia.

Type
Lecture
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.)

Footnotes

This paper was presented, in part, as the Maudsley Hospital Bequest Lecture at the Royal College of Psychiatrists' Winter Quarterly Meeting on 27 January 1988 in London by Dr Ming T. Tsuang.

References

American Psychiatric Association (1980) Diagnostic and Statistical Manual for Mental Disorders (3rd edn). Washington DC: APA.Google Scholar
Andreasen, N. C., Olsen, S. A., Dennert, J. W., et al (1982) Ventricular enlargement in schizophrenia: relationship to positive and negative symptoms. American Journal of Psychiatry, 139, 297302.Google ScholarPubMed
Andrews, D. F. (1972) Plots of high-dimensional data. Biometrics, 28, 125136.Google Scholar
Angrist, B., Rotrosen, J. & Gershon, S. (1980) Responses to apomorphine, amphetamine, and neuroleptics in schizophrenic subjects. Psychopharmacology, 67, 3138.CrossRefGoogle ScholarPubMed
Barnett, V. & Lewis, T. (1984) Outliers in Statistical Data (2nd edn). Chichester: Wiley.Google Scholar
Bassett, A. S., McGillivray, B. C., Jones, B. D., et al (1988) Partial trisomy chromosome 5 cosegregating with schizophrenia. Lancet, i, 799801.Google Scholar
Benes, F. M., Davidson, J. & Bird, E. D. (1986) Cytoarchitectural studies of cerebral cortex of schizophrenics. Archives of General Psychiatry, 43, 3135.Google Scholar
Bowers, M. B., Swigar, M. E., Jatlow, P. I., et al (1987) Early neuroleptic response: clinical profiles and plasma catecholamine metabolites. Journal of Clinical Psychopharmacology, 7, 8386.Google Scholar
Bradbury, T. N. & Miller, G. A. (1985) Season of birth in schizophrenia: a review of evidence, methodology, and etiology. Psychological Bulletin, 98, 569594.Google Scholar
Brown, W. A. & Herz, L. R. (1988) Neuroleptic response as a nosologic device. In Handbook of Schizophrenia, vol. 3 (eds M. T. Tsuang & J. C. Simpson). Amsterdam: Elsevier.Google Scholar
Chakraborty, R. & Hanis, C. L. (1987) Nonrandom sampling in human genetics: skewness and kurtosis. Genetic Epidemiology, 4, 87101.Google Scholar
Chapman, L. & Chapman, J. (1977) Selection of subjects in studies of cognition. Journal of Abnormal Psychology, 86, 1015.Google Scholar
Cloninger, C. R., Reich, T. & Yokoyama, S. (1983) Genetic diversity, genome organization, and investigation of the etiology of psychiatric diseases. Psychiatric Developments, 3, 225246.Google Scholar
Crow, T. J. (1980) Positive and negative schizophrenic symptoms and the role of dopamine. British Journal of Psychiatry, 139, 379386.Google Scholar
Crow, T. J. (1983) Is schizophrenia an infectious disease? Lancet, i, 173175.CrossRefGoogle Scholar
Crow, T. J., Berndl, K., Bogerts, B., et al (1987) Structural and functional deviations group report. In Biological Perspectives of Schizophrenia (eds H. Helmchen & F. A. Henn). Chichester: Wiley.Google Scholar
Dalen, P. (1972) One, two, or many? In Genetic Factors in Schizophrenia (ed. A. R. Kaplan). Springfield: Charles C. Thomas.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. British Journal of Psychiatry, Special Publication No. 4, 113184.Google Scholar
De Lisi, L. E. (1986) The use of positron emission tomography (PET) to image regional brain metabolism in schizophrenia and other psychiatric disorders: a review. In Handbook of Schizophrenia, Vol. 1 (eds H. A. Nasrallah & D. R. Weinberger). Amsterdam: Elsevier.Google Scholar
Elston, R. C. & Campbell, M. A. (1970) Schizophrenia: the evidence for the major gene hypothesis. Behavior Genetics, 1, 3.CrossRefGoogle ScholarPubMed
Faraone, S. & Tsuang, M. (1985) Quantitative models of the genetic transmission of schizophrenia. Psychological Bulletin, 98, 4166.Google Scholar
Faraone, S., Lyons, M. & Tsuang, M. (1988) Mathematical models of genetic transmission. In Handbook of Schizophrenia, Vol. 3 (eds M. T. Tsuang & J. C. Simpson). Amsterdam: Elsevier.Google Scholar
Faux, S. F., Shenton, M. E., McCarley, R. W., et al (1987) P200 topographic alterations in schizophrenia: evidence for left temporal–centroparietal amplitude deficits. Electroencephalic Clinical Neurophysiology, 40, 681687.Google Scholar
Feighner, J. P., Robins, E., Guze, S. B., et al (1972) Diagnostic criteria for use in psychiatric research. Archives of General Psychiatry, 26, 5763.CrossRefGoogle ScholarPubMed
Golden, R. & Meehl, P. (1979) Detection of the schizoid taxon with MMPI indicators. Journal of Abnormal Psychology, 88, 217233.Google Scholar
Haldane, J. B. S. (1941) The relative importance of principal and modifying genes in determining some human diseases. Journal of Genetics, 41, 149157.Google Scholar
Harris, H. & Smith, C. A. B. (1947) The sib-sib age of onset correlation among individuals suffering from a hereditary syndrome produced by more than one gene. Annual of Eugenics, 14, 309318.Google Scholar
Holzman, P. S. (1987) Recent studies of psychophysiology in schizophrenia. Schizophrenia Bulletin, 13, 4976.Google Scholar
Kendler, K., Gruenberg, A. & Tsuang, M. (1984) Outcome of schizophrenic subtypes defined by four diagnostic systems. Archives of General Psychiatry, 41, 149154.Google Scholar
Kendler, K., Gruenberg, A. & Tsuang, M. (1985) Subtype stability in schizophrenia. American Journal of Psychiatry, 142, 827832.Google ScholarPubMed
Kendler, K., Gruenberg, A. & Tsuang, M. (1988) A family study of the subtypes of schizophrenia. American Journal of Psychiatry, 145, 5762.Google Scholar
Kennedy, J. L., Giuffra, L. A., Moises, H. W., et al (1988) Evidence against linkage of schizophrenia to markers on chromosome 5 in a northern Swedish pedigree. Nature, 336, 167169.Google Scholar
Kidd, K. K. & Cavalli-Sforza, L. L. (1973) An analysis of the genetics of schizophrenia. Social Biology, 20, 254.Google Scholar
Knight, J. G., Knight, A. & Pert, C. B. (1987) Is schizophrenia a virally triggered antireceptor autoimmune disease? In Biological Perspectives of Schizophrenia (eds H. Helmchen & F. A. Henn). Chichester: Wiley.Google Scholar
Lander, E. S. (1988) Splitting schizophrenia. Nature, 336, 105106.Google Scholar
Lewis, S., Reveley, A., Reveley, M., et al (1987) The familial/sporadic distinction as a strategy in schizophrenia research. British Journal of Psychiatry, 151, 306313.Google Scholar
Lipton, R. B., Levy, D. L., Holzman, P. S., et al (1983) Eye movement dysfunctions in psychiatric patients: a review. Schizophrenia Bulletin, 9, 1332.CrossRefGoogle ScholarPubMed
Matthysse, S. W. & Kidd, K. K. (1976) Estimating the genetic contribution to schizophrenia. American Journal of Psychiatry, 133, 185.Google Scholar
McGuffin, P., Farmer, A. & Gottesman, I. (1987) Is there really a split in schizophrenia? The genetic evidence. British Journal of Psychiatry, 150, 581592.CrossRefGoogle ScholarPubMed
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: New Approaches to Research and Treatment (eds L. C. Wynne, R. L. Cromwell & S. Matthysse). New York: Wiley.Google Scholar
Meehl, P. E. (1973) MAXCOV-HITMAX: A taxonomic search method for loose genetic syndromes. In Psychodiagnosis: Selected Papers (ed. P. E. Meehl). New York: Norton.Google Scholar
Rao, D. C., Vogler, G. P., McGue, M., et al (1987) Maximum-likelihood estimation of familial correlations from multivariate quantitative data on pedigrees: a general method and examples. American Journal of Human Genetics, 41, 11041116.Google Scholar
Rao, D. C. & Wette, R. (1987) Nonrandom sampling in genetic epidemiology: maximum likelihood methods for multifactorial analysis of quantiative data ascertained through truncation. Genetic Epidemiology, 4, 357376.Google Scholar
Reveley, A., Reveley, M. & Murray, R. (1984) Cerebral ventricular enlargement in non genetic schizophrenia. British Journal of Psychiatry, 147, 233240.Google Scholar
Seidman, L. J. (1983) Schizophrenia and brain dysfunction: an integration of recent neurodiagnostic findings. Psychological Bulletin, 94, 195238.Google Scholar
Sherrington, R., Brynjolfsson, J., Petursson, H., et al (1988) Localization of a susceptibility locus for schizophrenia on chromosome 5. Nature, 336, 164166.CrossRefGoogle ScholarPubMed
Shur, E. (1982) Season of birth in high and low genetic risk schizophrenics. British Journal of Psychiatry, 140, 410415.CrossRefGoogle ScholarPubMed
Slater, E. (1947) Genetical causes of schizophrenic symptoms. Monatsschrift für Psychiatre und Neurologie, 113, 5058. (Reprinted in Man, Mind and Heredity (eds J. Shields I. I. Gottesman).)CrossRefGoogle ScholarPubMed
Weinberger, D. R., Bigelow, L. B., Kleinman, J. E., et al (1980) Cerebral ventricular enlargement in chronic schizophrenia: an association with poor response to treatment. Archives of General Psychiatry, 37, 1113.CrossRefGoogle ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.