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Genotypes, Phenotypes, and the Brain

A Search for Connections in Schizophrenia

Published online by Cambridge University Press:  02 January 2018

Ming T. Tsuang*
Affiliation:
Harvard Departments of Psychiatry and Epidemiology and Brockton/West Roxbury VA Medical Center; and Head, Department of Psychiatry, Harvard Medical School at Massachusetts Mental Health Center, 74 Fenwood Road, Boston, MA 02115, USA

Extract

The history of psychiatric research on genotypes, phenotypes, and the brain reveals much about the role of these concepts in our past and current understanding of schizophrenia and other psychiatric illnesses. Although interest in each topic is old by the standards of our young science, all have waxed and waned in their influence during our brief history. By ‘genotype’ I mean the hereditary constitution consisting of the genetic code, and by ‘phenotype’ I mean the physical expression of those genes throughout the life cycle of the individual. The relevance of the genotype to our field was recognised during the time of Charles Darwin, and reflected in the views of Henry Maudsley. Early optimism about the role that genetics would play in our understanding of mental disorder was tempered by the failure to find patterns of inheritance that corresponded to those described by Mendel. Enthusiasm about the study of genetic influences on human attributes was further attenuated when pseudo-genetics was embraced as a rationale for the horror of genocide. There has been a long and honourable history of genetic research in psychiatry, sustained by individuals such as Dr Eliot Slater (the 35th Maudsley lecturer and then Director of the Medical Research Council Psychiatric Genetics Research Unit at the Maudsley Hospital), but a renewal of the early excitement about genetic research has been engendered largely by recent developments in molecular biology.

Type
Review Articles
Copyright
Copyright © Royal College of Psychiatrists, 1993 

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References

American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM-III-R). Washington, DC: APA.Google Scholar
Andreasen, N. C. (1982) Negative syndromes in schizophrenia: definition and reliability. Archives of General Psychiatry, 39, 784788.Google Scholar
Andreasen, N. C. (1984a) The Scale for Assessment of Negative Symptoms (SANS). Iowa City, Iowa: University of Iowa.Google Scholar
Andreasen, N. C. (1984b) The Scale for Assessment of Positive Symptoms (SAPS). Iowa City, Iowa: University of Iowa.Google Scholar
Andreasen, N. C. (1985) Positive vs. negative schizophrenia: a critical evaluation. Schizophrenia Bulletin, 11, 380389.Google Scholar
Andreasen, N. C. & Olsen, S. (1982) Negative vs. positive schizophrenia. Archives of General Psychiatry, 39, 789794.Google Scholar
Arndt, S., Alliger, R. J. & Andreasen, N. C. (1991) The distinction of positive and negative symptoms. British Journal of Psychiatry, 158, 317322.Google Scholar
Bear, D. M. (1983) Hemispheric specialization and the neurology of emotion. Neurological Review, 40, 195202.Google ScholarPubMed
Berrios, G. E. (1985) Positive and negative symptoms and Jackson: a conceptual history. Archives of General Psychiatry, 42, 9597.Google Scholar
Bleuler, E. (1911) Dementia Praecox or the Group of Schizophrenias (trans by Zinkin, J., 1950). New York: International Universities Press.Google Scholar
Breier, A., Wolkowitz, O. M., Doran, A. R., et al (1987) Neuroleptic responsivity of negative and positive symptoms in schizophrenia. American Journal of Psychiatry, 144, 15491555.Google ScholarPubMed
Buchsbaum, M. S. (1990) The frontal lobes, basal ganglia, and temporal lobes as sites for schizophrenia. Schizophrenia Bulletin, 14, 379389.CrossRefGoogle Scholar
de Clerambault, G. (1942) Ouvre Psychiatrique. Paris: Presses Universitaires de France.Google Scholar
Crow, T. J. (1980) Molecular pathology of schizophrenia: more than one disease process? British Medical Journal, 12, 6667.Google Scholar
Crow, T. J. (1985) The two syndrome concept: origins and current status. Schizophrenia Bulletin, 11, 471486.Google Scholar
Crow, T. J. (1987) Two syndromes of schizophrenia as one pole of the continuum of psychosis: a concept of the nature of the pathogen and its genomic locus. In Handbook of Schizophrenia, Vol. 2: Neurochemistry and Neuropharmacology of Schizophrenia (eds Henn, F. & DeLisi, L.), pp. 1748. Amsterdam: Elsevier Science.Google Scholar
Cutting, J. (1992) The role of right hemisphere dysfunction in psychiatric disorders. British Journal of Psychiatry, 160, 583588.Google Scholar
DeLisi, 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: The Neurology of Schizophrenia (eds Nasrallah, H. & Weinberger, D.), pp. 309324. New York: Elsevier Science.Google Scholar
Dworkin, R. H. & Lenzenweger, M. F. (1984) Symptoms and the genetics of schizophrenia: implications for diagnosis. American Journal of Psychiatry, 14, 15411546.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.Google Scholar
Goetz, K. L. & van Kammen, D. P. (1986) Computerized axial tomography scans and subtypes of schizophrenia: a review. Journal of Nervous and Mental Disease, 174, 3144.Google Scholar
Goldberg, S. C. (1985) Negative and deficit symptoms in schizophrenia respond to neuroleptics. Schizophrenia Bulletin, 11, 453456.Google Scholar
Gur, R. E., Skolnick, B. E., Gur, R. C., et al (1983) Brain function in psychiatric disorders - I. Regional cerebral blood flow in medicated schizophrenics. Archives of General Psychiatry, 40, 12501254.Google Scholar
Gur, R. E., Skolnick, B. E., Gur, R. C., Gur, R. C., Skolnick, B. E., et al (1985) Brain function in psychiatric disorders - III. Regional cerebral blood flow in unmedicated schizophrenics. Archives of General Psychiatry, 42, 329334.Google Scholar
Henn, F. A. & Nasrallah, H. A., (eds) (1982) Schizophrenia as a Brain Disease. New York: Oxford University Press.Google Scholar
Johnstone, E. C., Crow, T. J., Firth, C. D., et al (1986) Mechanisms of the antipsychotic effect in the treatment of acute schizophrenia. Lancet, i, 848851.Google Scholar
Kay, S. R., Opler, L. A. & Fiszbein, A. (1986) Significance of positive and negative syndromes in chronic schizophrenia. British Journal of Psychiatry, 149, 439448.Google Scholar
Keefe, R. S. E., Mohs, R. C., Losonczy, M. F., et al (1987) Characteristics of very poor outcome schizophrenia. American Journal of Psychiatry, 144, 889895.Google Scholar
Kemali, D. (1985) Clinical and neuropsychological correlates of cerebral ventricular enlargement in schizophrenia. Journal of Psychiatric Research, 19, 587596.CrossRefGoogle ScholarPubMed
Kendler, K. S., Gruenberg, A. M. & Tsuang, M. T. (1988) A family study of the subtypes of schizophrenia. American Journal of Schizophrenia, 145, 5762.Google Scholar
Kraepelin, E. (1913) Dementia Praecox and Paraphrenia (trans by Barclay, R. M., 1919). Huntington, New York: Robert E. Krieger (1971).Google Scholar
Kretschmer, E. (1921) Physique and Character: An Investigation of the Nature of Constitution and of Theory of Temperament. New York: Cooper Square (1970).Google Scholar
Maudsley, H. (1905) Address in medicine. British Medical Journal, ii, 227231. (Cited in Turner, 1988.) Google Scholar
McGlashan, T. H. & Fenton, W. S. (1992) The positive-negative distinction in schizophrenia: review of natural history validators. Archives of General Psychiatry, 49, 6372.Google Scholar
Pfohl, B. & Winokur, G. (1982a) The evolution of symptoms in institutionalized hebephrenic/catatonic schizophrenics. British Journal of Psychiatry, 141, 567572.Google Scholar
Pfohl, B. & Winokur, G. (1982b) Schizophrenia: course and outcome. In Schizophrenia as a Brain Disease (eds Henn, F. & Nasrallah, H.). New York: Oxford University Press.Google Scholar
Pfohl, B. & Winokur, G. (1983) The micropsychopathology of hebephrenic/catatonic schizophrenia. Journal of Nervous and Mental Disease, 171, 296300.Google Scholar
Pogue-Geile, M. F. & Harrow, M. (1985) Negative symptoms in schizophrenia: their longitudinal course and prognostic importance. Schizophrenia Bulletin, 11, 427439.Google Scholar
Pogue-Geile, M. F. & Harrow, M. & Zubin, J. (1988) Negative symptomatology and schizophrenia: a conceptual and empirical review. International Journal of Mental Health, 16, 345.Google Scholar
Pope, H. G. & Lipinski, J. F. Jr (1978) Diagnosis in schizophrenia and manic depressive illness: a reassessment of the specificity of ‘schizophrenic’ symptoms in the light of current research. Archives of General Psychiatry, 35, 811828.Google Scholar
Robins, E. & Guze, S. B. (1970) Establishment of diagnostic validity in psychiatric illness: its applications to schizophrenia. American Journal of Psychiatry, 126, 983998.Google Scholar
Sackeim, H. A., Greenberg, M. S., Weiman, M. A., et al (1982) Hemispheric asymmetry in the expression of positive and negative emotions: neurologic evidence. Archives of Neurology, 39, 210218.Google Scholar
Seidman, L. J. (1983) Schizophrenia and brain dysfunction: an integration of recent neurodiagnostic findings. Psychology Bulletin, 94, 195238.Google Scholar
Strauss, J. S., Carpenter, W. T. & Bartko, J. J. (1974) The diagnosis and understanding of schizophrenia - III. Speculations on the processes that underlie schizophrenic symptoms and signs. Schizophrenia Bulletin, 1, 6169.Google Scholar
Tsuang, M. T. & Winokur, G. (1974) Criteria for subtyping schizophrenia: clinical differentiation of hebephrenic and paranoid and nonparanoid schizophrenics. Archives of General Psychiatry, 31, 4347.Google Scholar
Tsuang, M. T. & Winokur, G., Woolson, R. F. & Fleming, J. A. (1979) Long-term outcome of major psychoses: I. Schizophrenia and affective disorders compared with psychiatrically symptom-free surgical conditions. Archives of General Psychiatry, 36, 12951301.Google Scholar
Tsuang, M. T., Winokur, G. & Crowe, R. R. (1980) Morbidity risks of schizophrenia and affective disorders among first-degree relatives of patients with schizophrenia, mania, depression and surgical conditions. British Journal of Psychiatry, 137, 497504.CrossRefGoogle ScholarPubMed
Tsuang, M. T., Lyons, M. J. & Faraone, S. V. (1987) The contribution of genetic research to diagnostic issues in schizophrenia. In Biological Perspectives in Schizophrenia (eds Heimchen, H. & Henn, F.), pp. 5770. New York: John Wiley & Sons.Google Scholar
Tsuang, M. T., Lyons, M. J. & Faraone, S. V. (1990) Heterogeneity of schizophrenia: conceptual models and analytic strategies. British Journal of Psychiatry, 156, 1726.Google Scholar
Tsuang, M. T., Lyons, M. J. & Faraone, S. V., Gilbertson, M. W. & Faraone, S. V. (1991) Genetic transmission of negative and positive symptoms in biological relatives of schizophrenics. In Positive and Negative Schizophrenia (eds Marneros, A., Tsuang, M. & Andreasen, N.), pp. 265291. Berlin: Springer-Verlag.Google Scholar
Turner, T. (1988) Henry Maudsley - psychiatrist, philosopher and entrepreneur. Psychological Medicine, 18, 551574.Google Scholar
Weinberger, D. R. (1987) Implications for normal brain development for the pathogenesis of schizophrenia. Archives of General Psychiatry, 44, 660669.Google Scholar
World Health Organization (1978) Mental Disorders: Glossary and Guide to their Classification in Accordance with the Ninth Revision of the International Classification of Diseases (1CD-9). Geneva: WHO.Google Scholar
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