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Genetic factors in the response to neuroleptics in schizophrenia: a psychopharmacogenetic study

Published online by Cambridge University Press:  09 July 2009

Joe Galdi ,
Ronald O. Rieder ,
David Silber  and
Roland R. Bonato
Joe Galdi*
Affiliation:
Biometric Laboratory, George Washington University, Bethesda, Maryland, USA
Ronald O. Rieder
Affiliation:
Biometric Laboratory, George Washington University, Bethesda, Maryland, USA
David Silber
Affiliation:
Biometric Laboratory, George Washington University, Bethesda, Maryland, USA
Roland R. Bonato
Affiliation:
Biometric Laboratory, George Washington University, Bethesda, Maryland, USA
*
1Address for correspondence: Dr Joe Galdi, Department of Psychiatry, University of Cincinnati College of Medicine, Rm 7303, MSB, Cincinnati, OH 45267, USA.
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Synopsis

A psychopharmacogenetic strategy was used to investigate a genetic heterogeneity model of schizophrenia. This model consisted of various genetic subtypes represented by patients classified hypothetically according to the types and genealogical (Mendelian) patterns of illnesses in first-degree relatives. The effect of neuroleptics on these subtypes (drug x genetic subtype interactions) were tested for evidence of post-treatment responses which discriminated between them. The findings revealed that schizophrenics who had depressed relatives tended to exhibit (1) depression and more severe pseudoparkinsonism irrespective of types of neuroleptics, and (2) greater remission of paranoid-hostility symptoms when treated with neuroleptics of the aliphatic-piperadine type. Schizophrenics who had schizophrenic relatives failed to show these responses.

Interpretation of these findings emphasized the recognition of these responses as arising from neuroleptic-induced alterations of defective neurologic-neurochemical systems underlying this subtype and as ‘pharmacogenetic criteria’ by which it can be discriminated.

Type
Research Article
Information
Psychological Medicine , Volume 11 , Issue 4 , November 1981 , pp. 713 - 728
Copyright
Copyright © Cambridge University Press 1981

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References

REFERENCES

Akiskal, H. S. & McKinney, W. T. (1975). Overview of recent research in depression. Archives of General Psychiatry 32, 285–305.CrossRefGoogle ScholarPubMed
Akiskal, H. S. & Webb, W. L. (1978). Psychiatric Diagnosis: Explorations of Biological Predictors. Spectrum: New York.Google Scholar
d'Alarcón, R. & Carney, M. W. P. (1969). Severe depressive mood changes following slow-release intramuscular fluphenazine injection. British Medical Journal i, 564–567.CrossRefGoogle Scholar
American Psychiatric Association (1952). Diagnostic and Statistical Manual of Mental Disorders (DSM-I). APA: Washington, D.C.Google Scholar
American Psychiatric Association (1968). Diagnostic and Statistical Manual of Mental Disorders (DSM-II). APA: Washington, D.C.Google Scholar
American Psychiatric Association (1980). Diagnostic and Statistical Manual of Mental Disorders (DSM-III). APA: Washington, D.C.Google Scholar
Appleton, W. S. (1976). Third psychoactive drug usage guide. Diseases of the Nervous System 37, 39–51.Google ScholarPubMed
Astrup, C. (1979). The Chronic Schizophrenias. Universitets-forlaget: Oslo.Google Scholar
Avrutskii, G. Y. (1964). Some unfavorable effects of aminazine medication on the manifestations and course of schizophrenia. In Problems of Psychopharmacology (ed. Rokhlin, L. L.), pp. 61–72. Davey: New York.Google Scholar
Bonato, R. R., Guy, W., Cleary, P. & Yang, K. (1970). BLIPS: the information processing system for the ECDEU program. Psychopharmacology Bulletin 6, 22–47.Google Scholar
Bowers, M. B. & Astrachan, B. M. (1967). Depression in acute schizophrenic psychosis. American Journal of Psychiatry 123, 976–979.CrossRefGoogle ScholarPubMed
Bunney, B. S. & Aghajanian, G. K. (1978). Mesolimbic and mesocortical dopaminergic systems: physiology and pharmacology. In psychopharmacology: A Generation of Progress (ed. Lipton, M. A., DiMascio, A. and Killiam, K. F.), pp. 159–169Raven Press: New York.Google Scholar
Burdock, E. I., Hakerem, G., Hardesty, A. S. & Zubin, J. (1960). A ward behavior scale for use with mental hospital patients. Journal of Clinical Psychology 16, 246–247.3.0.CO;2-Y>CrossRefGoogle Scholar
Carlsson, A. (1978). The neuropharmacology of schizophrenia: specificity for neurotransmitter systems. In Psychiatric Diagnosis: Exploration of Biological Predictors (ed. Akiskal, H. S. and Webb, W. L.), pp. 247–262. Spectrum: New York.Google Scholar
Carpenter, W. T., McGlashan, T. H. & Strauss, J. S. (1977). The treatment of acute schizophrenia without drugs: an investigation of some current assumptions. American Journal of Psychiatry 134, 14–20.Google ScholarPubMed
Casey, J. F., Bennett, I. F. & Lindley, C. J. (1960). Drug therapy of schizophrenia: a controlled study of the relative effectiveness of chlorpromazine, promazine, phenobarbitol, and placebo. Archives of General Psychiatry 117, 997–1003.Google Scholar
Celesia, G. G. & Wanamaker, W. M. (1972). Psychiatric disturbances in Parkinson's disease. Diseases of the Nervous System 33, 577–582.Google ScholarPubMed
Cooper, J. R., Bloom, F. E. & Roth, R. H. (1978). The Biochemical Basis of Neuropharmacology. Oxford: New York.Google Scholar
Davis, J. M. (1976). Comparative doses and costs of antipsychotic medication. Archives of General Psychiatry 33, 858–861.CrossRefGoogle ScholarPubMed
Donlon, P. T. & Stenson, R. L. (1976). Neuroleptic induced extrapyramidal symptoms. Diseases of the Nervous System 37, 629–635.Google ScholarPubMed
Donlon, P. T., Rada, R. T. & Arora, K. K. (1976). Depression and the reintegration phase of acute schizophrenia. American Journal of Psychiatry 133, 1265–1268.Google ScholarPubMed
Duvoisin, R. C. (1968). Neurological reactions to psychotropic drugs. In psychopharmacology: A Review of Progress 1957–1967 (ed. Efron, D. H.), pp. 561–574. PHS No. 1836. US Government Printing Office: Washington, D.C.Google Scholar
Eleftheriou, B. E. (ed.) (1975). Psychopharmacogenetics. Plenum Press: New York.CrossRefGoogle Scholar
Feighner, J. P., Robins, E., Guze, S. B., Woodruff, R. A., Winokur, G. & Munoz, R. (1972). Diagnostic criteria for use in psychiatric research. Archives of General Psychiatry 26, 57–63.CrossRefGoogle ScholarPubMed
Fish, F. J. (1962). Schizophrenia. Williams & Wilkins: Baltimore.Google Scholar
Floru, L., Heinrich, K. & Wittek, F. (1975). The problem of postpsychotic schizophrenic depression and their pharmacological induction. International Pharmacopsychiatry 10, 230–239.CrossRefGoogle ScholarPubMed
Food and Drug Administration (1977). General Considerations for the Clinical Evaluation of Drugs. HEW (FDA) No. 77–3040. US Government Printins, Office: Washington, D.C.Google Scholar
Fowler, R. C., McCabe, M. S., Cadoret, R. J. & Winokur, G. (1972). The validity of good prognosis schizophrenia. Archives of General Psychiatry 26, 182–185.CrossRefGoogle ScholarPubMed
Galdi, J., Rieder, R. O. & Bonato, R. (1981 a). Pharmacogenetic predictors of length of hospital stay in recently admitted schizophrenics. (Submitted for publication.)Google Scholar
Galdi, J., Kelly, J. T., Rieder, R. O., Bonato, R. R. & Schiele, B. C. (1981 b). A test of the validity of pharmacogenetic pseudoparkinsonism in schizophrenia. (Submitted for publication.)Google Scholar
Gallant, D. M., Bishop, M. P., Free, S. M., Goldberg, S. C. & Simpson, G. M. (1971). Evaluation of efficacy of psychotropic agents in schizophrenic populations. In Principles and Problems in Establishing the Efficacy of Psychotropic Agents (ed. Levine, J., Schiele, B. and Bouthilet, L.), pp. 59–90. US Government Printing Office: Washington, D.C.Google Scholar
Gershon, E. S., Bunney, W. E., Leckman, J. F., Van Eerdewegh, M. & DeBauche, B. A. (1976). The inheritance of affective disorders: a review of data and hypotheses. Behavior Genetics 6, 227–261.CrossRefGoogle ScholarPubMed
Goldberg, S. C., Cole, S. C. & Clyde, D. J. (1963). Factor analysis of ratings of schizophrenic behavior. Psychopharmacology Service Center Bulletin 2, 23–28.Google ScholarPubMed
Goldstein, M. J. (1970). Premorbid adjustment, paranoid status, and patterns of response to phenothiazine in acute schizophrenia. Schizophrenia Bulletin 3, 24–37.CrossRefGoogle Scholar
Gottesman, I. I. & Shields, J. (1976). A critical review of recent adoption, twin, and family studies of schizophrenia: behavioral genetics perspectives. Schizophrenia Bulletin 2, 360–400.CrossRefGoogle ScholarPubMed
Guy, W. (1976). ECDEU Assessment Manual For Psychopharmacology (Revised). DHEW No. (ADM) 76–338. US Government Printing Office: Washington, D.C.Google Scholar
Guy, W., Cleary, P. & Bonato, R. R. (1974). Methodological considerations of a large central data system. In Neuropsychopharmacology, pp. 79–87. International Congress Series No. 359. Excerpta Medica: Amsterdam.Google Scholar
Hartmann, W., Kind, J., Meyer, J. E., Muller, P. & Steuber, H. (1980). Neuroleptic drugs and the prevention of relapse in schizophrenia: a workshop report. Schizophrenia Bulletin 6, 536–543.CrossRefGoogle ScholarPubMed
Hogarty, G. E., Schooler, N. R., Ulrich, R., Mussare, F., Ferro, P. & Herron, E. (1979). Fluphenazine and social therapy in the aftercare of schizophrenic patients. Archives of General Psychiatry 36, 1283–1294.CrossRefGoogle ScholarPubMed
Honigfeld, G., Gillis, R. D. & Klett, C. J. (1966). NOSIE-30: a treatment sensitive ward behavior scale. Psychological Reports 19, 180–182.CrossRefGoogle ScholarPubMed
Inouye, E. (1963). Similarity and dissimilarity of schizophrenia in twins. Proceedings of the Third World Congress of Psychiatry 1, 524–530.Google Scholar
Kalow, W. & LaBlanc, A. E. (1975). Implications of psychopharmacogenetic research. In Psychopharmacogenetics (ed. Eleftheriou, B. E.), pp. 33–42. Plenum Press: New York.CrossRefGoogle Scholar
Kayton, L., Beck, J. & Koh, S. D. (1976). Postpsychotic state, convalescent environment, and therapeutic relationship in schizophrenic outcome. American Journal of Psychiatry 133, 1269–1274.Google ScholarPubMed
Kerlinger, F. N. & Pudhuzar, E. J. (1973). Multiple Regression in Behavioral Research. Holt, Rinehart & Winston: New York.Google Scholar
Klein, D. F. (1968). Diagnosis and pattern of reaction to drug treatment: clinically derived foundations. In Classification in Psychiatry and Psychopathology (ed. Katz, M. M., Cole, J. O. and Barton, W. E.), pp. 466–482. DHEW No. (HSM) 72–9015. US Government Printing Office: Washington, D.C.Google Scholar
Klein, D. F. & Davis, J. (1969). Diagnosis and Treatment of Psychiatric Disorders. Williams & Wilkins: Baltimore.Google Scholar
Klein, D. F. & Rosen, B. (1973). Premorbid asocial adjustment and response to phenothiazine treatment among schizophrenic inpatients. Archives of General Psychiatry 29, 480–485.CrossRefGoogle ScholarPubMed
Kraepelin, E. (1919). Dementia Praecox and Paraphrenia. Livingstone: Edinburgh.Google Scholar
Lehmann, H. (1975). Psychopharmacological treatment of schizophrenia. Schizophrenia Bulletin 13, 27–45.CrossRefGoogle Scholar
Lorr, M., Klett, C. J. & McNair, D. M. (1963). Syndromes of Psychosis. Pergamon: London.Google Scholar
Marjot, D. H. (1969). Depression following fluphenazine treatment (letter). British Medical Journal i, 780.CrossRefGoogle Scholar
Marsden, C. D. & Jenner, P. (1980). The pathophysiology of extrapyramidal side-effects of neuroleptic drugs. Psychological Medicine 10, 55–72.CrossRefGoogle ScholarPubMed
Mathysse, S. & Kidd, K. K. (1976). Estimating the genetic contribution in schizophrenia. American Journal of Psychiatry 131; 185–191.Google Scholar
Mayr, E. (1972). Consequences of recent research findings. In Genetic Factors in ‘Schizophrenia’ (ed. Kaplan, A. R.), pp. 164–173. C. C. Thomas: Springfield, Ill.Google Scholar
McGlashan, T. H. (1973). The Documentation of Clinical Psychotropic Drug Trials. DHEW No. (HSM) 73–9038. US Government Printing Office: Washington, D.C.Google Scholar
McGlashan, T. H. & Carpenter, W. T. (1976 a). Postpsychotic depression in schizophrenia. Archives of General Psychiatry 33, 231–239.CrossRefGoogle ScholarPubMed
McGlashan, T. H. & Carpenter, W. T. (1976 b). An investigation of the postpsychotic depressive syndrome. American Journal of Psychiatry 133, 14–19.Google ScholarPubMed
McKinnon, B. L. (1977). Postpsychotic depression and the need for personal significance. American Journal of Psychiatry 134, 427–429.Google Scholar
Meltzer, H. Y. (1979). Biology of schizophrenia subtypes. Schizophrenia Bulletin 5, 460–479.CrossRefGoogle ScholarPubMed
Mendlewicz, J., Fieve, R. R., Rainer, J. D. & Fleiss, J. L. (1972). Manic-depressive illness: a comparative study of patients with and without a family history. British Journal of Psychiatry 120, 523–530.CrossRefGoogle ScholarPubMed
Mendlewicz, J., Fleiss, J. L., Cataldo, M. & Rainer, J. D. (1975). Accuracy of the family history method in affective illness. Archives of General Psychiatry 32, 309–314.CrossRefGoogle ScholarPubMed
Mitsuda, H. (1967). Clinical genetics in psychiatry. In Clinical Genetics in Psychiatry (ed Mitsuda, H.), pp. 3–21. Igaku Shion: Tokyo.Google Scholar
Moore, K. E. & Kelly, P. H. (1978). Biochemical pharmacology of mesolimbic and mesocortical dopaminergic neurons. In Psychopharmacology: A Generation of Progress (ed. Lipton, M. A., DiMascio, A. and Killam, K. F.), pp. 221–234. Raven Press: New York.Google Scholar
Murray, R. M. & Murphy, D. L. (1978). Drug response and psychiatric nosology. Psychological Medicine 8, 667–681.CrossRefGoogle ScholarPubMed
National Institute of Mental Health – Psychopharmacology Research Branch (1967). Differences in clinical effects of three phenothiazines in acute schizophrenia. Diseases of the Nervous System 28, 269–383.Google Scholar
Ollerenshaw, D. P. (1973). The classification of the functional psychoses. British Journal of Psychiatry 122, 777–788.CrossRefGoogle ScholarPubMed
Overall, J. E. & Klett, C. J. (1972). Applied Multivariate Analysis. McGraw-Hill: New York.Google Scholar
Planansky, K. & Johnston, R. (1978). Depressive syndrome in schizophrenia. Acta psychiatrica scandinavica 57, 207–218.CrossRefGoogle ScholarPubMed
Pope, H. G. & Lipinski, J. F. (1978). Diagnosis in schizophrenia and manic-depressive illness. Archives of General Psychiatry 35, 811–828.CrossRefGoogle ScholarPubMed
Rieder, R. O. & Gershon, E. S. (1978). Genetic strategies in biological psychiatry. Archives of General Psychiatry 35, 866–873.CrossRefGoogle ScholarPubMed
Robins, A. H. (1976). Depression in patients with Parkinsonism. British Journal of Psychiatry 128, 141–145.CrossRefGoogle ScholarPubMed
Rosenthal, D. (1970). Genetic Theory and Abnormal Behavior. McGraw-Hill: New York.Google Scholar
Rosenthal, D. (1977). Searches for the mode of genetic transmission in schizophrenia. Schizophrenia Bulletin 5, 59–86.Google Scholar
Roy, A. (1980). Depression in chronic paranoid schizophrenia. British Journal of Psychiatry 137, 138–139.CrossRefGoogle ScholarPubMed
Rüdin, E. (1916). Zur Vererbung end Neuentstehung der Dementia Praecox. Springer Verlag: Berlin.Google Scholar
Sachar, E. J., Mason, J. W. & Kolmer, H. A. (1963). Psychoencdocrine aspects of acute schizophrenic reactions. Psychosomatic Medicine 25, 510–537.CrossRefGoogle ScholarPubMed
Sachar, E. J., Kanter, S. S. & Buie, D. (1970). Psychoendocrinology of ego disintegration. American Journal of Psychiatry 126, 1067–1078.CrossRefGoogle ScholarPubMed
Schulz, B. & Leonhard, K. (1940). Erbiologische-klinische Untersuchungen an Insegsamt 99 im Sinne Leonhards typische beziehungsweise atypischen Schizophrenien. Zentralblatt für die gesamte Neurologie und Psychiatrie 168, 587–613.CrossRefGoogle Scholar
Schwab, H. (1938). Die Katatonie auf Grund katamnestischer Untersuchungen. II. Die Erblichkeit der eigenlichen Katatonie. Zentralblatt für die gesamte Neurologie und Psychiatrie 163, 441–506.CrossRefGoogle Scholar
Shanfield, S., Tucker, G. J. & Harrow, M. (1970). The schizophrenic patient and depressive symptomatology. Journal of Nervous and Mental Disease 151, 203–210.CrossRefGoogle ScholarPubMed
Siever, L. J. & Gunderson, J. G. (1979), Genetic determinants of borderline conditions. Schizophrenia Bulletin 5, 268–276.CrossRefGoogle ScholarPubMed
Singh, M. M. (1976). Dysphoric response to neuroleptic treatment in schizophrenia and its prognostic significance. Diseases of the Nervous System 37, 191–204.Google ScholarPubMed
Singh, M. M. & Kay, S. R. (1979). Dysphoric response to neuroleptic treatment in schizophrenia: its relationship to autonomic arousal and prognosis. Biological Psychiatry 14, 277–294.Google ScholarPubMed
Slater, E. (1953). Psychotic and Neurotic Illnesses in Twins. HMSO: LondonGoogle ScholarPubMed
Slater, E. & Cowie, V. (1971). The Genetics of Mental Disorders. Oxford University Press: London.Google Scholar
Slater, E. & Roth, M. (1969). In Clinical Psychiatry (ed. Mayer-Gross, W., Slater, E. and Roth, M.), pp. 237–341. Oxford University Press: London.Google Scholar
Snyder, S., Greenberg, D. & Yamamura, H. I. (1974). Antischizophrenic drugs and brain cholinergic receptors. Archives of General Psychiatry 31, 58–61.CrossRefGoogle ScholarPubMed
Spitzer, R. L., Endicott, J. & Robins, E. (1978). Research diagnostic criteria. Archives of General Psychiatry 35, 773–782.CrossRefGoogle ScholarPubMed
Tsuang, M. T. (1967). A study of pairs of sibs both hospitalized for mental disorders. British Journal of Psychiatry 113, 283–300.CrossRefGoogle Scholar
van Putten, T. & May, P. R. A. (1978). Akinetic depression in schizophrenia. Archives of General Psychiatry 35, 1101–1107.CrossRefGoogle ScholarPubMed
Warburton, J. W. (1967). Depressive symptoms in Parkinson patients referred for thalamotomy. Journal of Neurology Neurosurgery and Psychiatry 30, 121–128.CrossRefGoogle ScholarPubMed
Winokur, G. (1978). Paranoid versus hebephrenic schizophrenia: a differentiation based on clinical and family (genetic) findings. In Biochemistry of Mental Disorders (ed. Usdin, E. and Mandell, A. J.), pp. 11–26. Marcel Dekker: New York.Google Scholar
Winokur, G., Behar, D., Van Valkenberg, C. & Lowry, M. (1978). Is a familial definition of depression both feasible and valid? Journal of Nervous and Mental Disease 166, 764–768.CrossRefGoogle ScholarPubMed
Wyatt, R. J. (1976). Biochemistry and schizophrenia (Part IV). The neuroleptics – their mechanism of action: a review of the biochemical literature. Psychopharmacology Bulletin 12, 5–50.Google ScholarPubMed
Zerbin-Rudin, E. (1973). Genetic research and the theory of schizophrenia. In Annual Review of the Schizophrenic Syndrome (ed. Cancro, R.), pp. 302–324. Brunner/Mazel: New York.Google Scholar
Zhislin, S. G. (1964). The changing symptomatology and evolution of psychoses in modern psychotropic medication. In Problems of Psychopharmacology (ed. Rohklin, L. L.), pp. 51–60. Davey: New York.Google Scholar