Skip to main content
SpringerLink
Log in

Schizophrenia Epigenesis?

  • Published:
Theoretical Medicine and Bioethics Aims and scope Submit manuscript

Abstract

I begin by examining how genetics drivesschizophrenia research, and raise both familiar andrelatively novel criticisms of the evidence putativelysupporting the genetic basis of schizophrenia. Inparticular, I call attention to a set of concernsabout the effects of placentation on concordance ratesof schizophrenia in monozygotic twins, which furtherweakens the case for schizophrenia's so-called stronggenetic component. I then underscore two criticalpoints. First, I emphasize the importance of takingseriously considerations about the complexity of bothontogenesis and the development of hereditarydiseases. The recognition of developmentalconstraints and supports is crucial, for attention todevelopment exposes the naivete of too many models ofgene action in the aetiology of disease. Secondly, Iattend to those schizophreniologists who ignoremethodological criticisms and thus presume a geneticbasis for schizophrenia, and then seek the ‘schizophrenic genotype’ lacking an adequatephenotype. In response I attempt to demonstrate thenecessity of a sustained effort at characterizing thephenotype of schizophrenia as an enabling conditionfor the whole enterprise of psychiatric genetics – andfor psychiatry itself. Without the organism-levelphenotype, research at the level of genes will remainunproductive – assuming of course that research at thegenetic level is appropriate at all.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Kety SS. From Rationalization to Reason. Am J Psychiatry 1974; 131: 957–963.

    Google Scholar 

  2. Rose S, Lewontin RC, Kamin LJ. Not in Our Genes: Biology, Ideology, and Human Nature. New York: Penguin, 1984.

    Google Scholar 

  3. Marshall JR. The genetics of Schizophrenia: Axiom or hypothesis? In Bentall RP, ed. Reconstructing Schizophrenia. New York: Routledge, 1990: 89–117.

    Google Scholar 

  4. Marshall JR. Schizophrenia and the need for a critical analysis of information. In Brittain, JM, ed., Consensus and Penalties for Ignorance in the Medical Sciences: Implications for Information Transfer. London: Taylor Graham, 1985.

    Google Scholar 

  5. Boyle M. Schizophrenia: A Scientific Delusion? New York: Routledge, 1990.

    Google Scholar 

  6. Jablensky A, Sartorius N, Ernberg G, et al. Schizophrenia: Manifestations, Incidence and Course in Different Cultures: A World Health Organization Ten-Country Study. Psychol Med 1992; 22(suppl. 20): 1–97.

    Google Scholar 

  7. Murray RM, Revely AM, McGuffin P. Genetic vulnerability to Schizophrenia. Psychiatr Clin North Am 1986; 9: 3–16.

    Google Scholar 

  8. Gottesman II, Shields J. Schizophrenia: The Epigenetic Puzzle. Cambridge: Cambridge University Press, 1982.

    Google Scholar 

  9. Andreasen NC, Shore D, Burke JD Jr, et al. Clinical phenomenology. Schizophrenia Bull 1988; 14: 345–363.

    Google Scholar 

  10. Cardno AG, McGuffin P. The molecular genetics of Schizophrenia. Neuropath Appl Neurobiol 1994; 20: 344–349.

    Google Scholar 

  11. Kendler KS, Gardner CO Jr. Twin studies of adult psychiatric and substance dependence disorders: are they biased by differences in the environmental experiences of monozygotic and dizygotic twins in childhood and adolescence? Psychol Med 1998; 28: 625–633.

    Google Scholar 

  12. Gottesman II. Schizophrenia Genesis: The Origins of Madness. New York: W.H. Freeman, 1991.

    Google Scholar 

  13. Marshall JR, Pettit AN. Discordant concordant rates. Bull Brit Psychol Soc 1985; 38: 6–9.

    Google Scholar 

  14. Gottesman II. Schizophrenia epigenesis: Past, present, and future. Acta Psychiatr Scand Suppl 1994; 384: 26–33.

    Google Scholar 

  15. Kringlen E. Genes and environment in mental illness: Perspectives and ideas for future research. Acta Psychiatr Scand Suppl 1993; 370: 79–84.

    Google Scholar 

  16. Torrey EF. Are We overestimating the genetic contribution to schizophrenia? Schizophrenia Bull 1992; 18: 159–170.

    Google Scholar 

  17. Slater E. (With the assistance of Shields J.). Psychotic and neurotic illnesses in twins. Medical Research Council Special Report Series No. 278. London: Her Majesty's Stationary Office, 1953.

    Google Scholar 

  18. Tienari P. Psychiatric illnesses in identical twins. Acta Psychiatr Scand Suppl 1963; 171: 1–195.

    Google Scholar 

  19. Kringlen E. Heredity and Environment in the Functional Psychoses. Oslo: Universitetsforlaget, 1967.

    Google Scholar 

  20. Essen-Möller E. twenty-one psychiatric cases and their MZ cotwins. Acta Genet Med Gemellol 1970; 19: 315–317.

    Google Scholar 

  21. Fischer M. Genetic and environmental factors in schizophrenia. Acta Psychiatr Scand Suppl 1973; 238: 1–158.

    Google Scholar 

  22. Gottesman II, Shields J. Contributions of twin studies to perspectives on schizophrenia. In: Maher BA, ed., Contributions to the Psychopathology of Schizophrenia. New York: Academic Press, 1977.

    Google Scholar 

  23. Kendler KS, Robinette CD. Schizophrenia in the national academy of sciencesnational research council twin registry: A 16 year update. Am J Psychiatry 1983; 140: 1551–1563.

    Google Scholar 

  24. Onstad S, Skre I, Torgersen S, et al. Twin concordance for DSM-III-R schizophrenia. Acta Psychiatr Scand 1991; 83: 395–401.

    Google Scholar 

  25. Phillips DIW. Twin studies in medical research: can they tell us whether diseases are genetically determined? Lancet 1993; 17 April: 1008–1009.

    Google Scholar 

  26. Davis JO, Phelps JA. Twins with schizophrenia: Genes or germs? Schizophrenia Bull 1995; 21: 13–18.

    Google Scholar 

  27. Adams W, Kendell RE, Hare EH, et al. Epidemiological evidence that maternal influenza contributes to the aetiology of schizophrenia: An analysis of Scottish, English and Danish data. Br J Psychiatry 1993; 163: 522–534.

    Google Scholar 

  28. Crow TJ. Prenatal exposure to influenza as a cause of schizophrenia: There are inconsistencies and contradictions in the evidence. British J Psychiatry 1994; 164: 588–592.

    Google Scholar 

  29. Hooper J. A new germ theory. Atlantic Monthly 1999; February: 41–53.

  30. Suvisaari J, Haukka J, Tanskanen A, et al. Association between prenatal exposure to poliovirus infection and adult schizophrenia. Am J Psychiatry 1999: 156; 1100–1102.

    Google Scholar 

  31. Davis JO, Phelps JA, Bracha HS. Prenatal development of monozygotic twins and concordance for schizophrenia. Schizophrenia Bull 1995; 21: 357–366.

    Google Scholar 

  32. Kallman FJ. The Genetics of Schizophrenia. New York: J.J. Augustin, 1938.

    Google Scholar 

  33. Walker E, Downey G, Caspi A. Twin studies of psychopathology: Why do the concordance rates vary? Schizophrenia Res 1991; 5: 211–221.

    Google Scholar 

  34. Kety SS, Rosenthal D, Wender PH, et al. The types and prevalence of mental illness in the biological and adoptive families of adopted schizophrenics. In: Rosenthal D, Kety SS, eds., The Transmission of Schizophrenia. Oxford: Pergamon, 1968: 345–362.

    Google Scholar 

  35. Kety SS, Rosenthal D, Wender PH, et al. Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic. In: Fieve RR, Rosenthal D, Brill H, eds., Genetic Research in Psychiatry. Baltimore: Johns Hopkins University Press, 1975.

    Google Scholar 

  36. Cassou B, Schiff M, Stewart J. Génétique et schizophrénie: ré-évaluation d'un consensus. Psychiatr Enfant 1980; 23: 87–201.

    Google Scholar 

  37. Gaines AD. Medical/psychiatric knowledge in France and the United States: Culture and sickness in history and biology. In: Gaines AD, ed., Ethnopsychiatry: The Cultural Construction of Professional and Folk Psychiatries. Albany: State University of New York Press, 1992: 171–201.

    Google Scholar 

  38. Weinberger DR. Schizophrenia: New genes and new phenes. Biol Psychiatry 1999; 46: 3–7.

    Google Scholar 

  39. Oyama S. The Ontogeny of Information: Developmental Systems and Evolution. Cambridge: Cambridge University Press, 1985.

    Google Scholar 

  40. Wahlsten D, Gottlieb G. The invalid separation of effects of nature and nurture: Lessons from animal experimentation. In: Sternberg RJ, Grigorenko E, eds., Intelligence, Heredity, and Environment. Cambridge: Cambridge University Press, 1997: 163–192.

    Google Scholar 

  41. Lewontin RC. The analysis of variance and the analysis of causes. Am J Hum Genet 1974; 26: 400–411.

    Google Scholar 

  42. Hogben L. Nature and Nurture. New York: W.W. Norton, 1933.

    Google Scholar 

  43. Sarkar S. From the Reaktionsnorm to the adaptive norm: The norm of reaction, 1909–1960. Biol Phil 1999; 14: 235–252.

    Google Scholar 

  44. Sarkar S. Genetics and Reductionism. Cambridge: Cambridge University Press, 1998.

    Google Scholar 

  45. Sarkar S. Lancelot Hogben, 1895–1975. Genetics 1996; 142: 655–660.

    Google Scholar 

  46. Strohman RC. Ancient Genomes, Wise Bodies, Unhealthy People: Limits of a Genetic Paradigm in Biology and Medicine. Perspect Biol Med 1993; 37: 112–145.

    Google Scholar 

  47. Wahlsten D. Insensitivity of the Analysis of Variance to Heredity-Environment Interaction. Behav Brain Sci 1990; 13: 109–161.

    Google Scholar 

  48. Wolf U. The genetic contribution to the phenotype. Hum Genet 1995; 95: 127–148.

    Google Scholar 

  49. Gottlieb G. Some conceptual deficiencies in 'developmental' behavior genetics. Hum Dev 1995; 38: 131–141.

    Google Scholar 

  50. Alper JS, Natowicz MR. On establishing the genetic basis of mental disease. Trends Neurosci 1993; 16: 387–389.

    Google Scholar 

  51. Needham J. (with the assistance of Hughes A.). A History of Embryology, 2nd ed. New York: Abelard-Schuman, 1959.

    Google Scholar 

  52. Waddington CH. Organisers and Genes. Cambridge: Cambridge University Press, 1940.

    Google Scholar 

  53. Waddington CH. The Evolution of an Evolutionist. Ithaca: Cornell University Press, 1975.

    Google Scholar 

  54. Thom R. An inventory of Waddingtonian concepts. In: Goodwin B, Saunders P, eds., Theoretical Biology: Epigenetic and Evolutionary Order from Complex Systems. Edinburgh: Edinburgh University Press, 1989: 1–7.

    Google Scholar 

  55. Hall BK. Evolutionary Developmental Biology, 2nd ed. New York: Chapman & Hall, 1998.

    Google Scholar 

  56. Gilbert SF. Induction and the origins of developmental genetics. In: Gilbert SF, ed., A Conceptual History of Modern Embryology. Baltimore: Johns Hopkins University Press, 1991: 181–206.

    Google Scholar 

  57. Needham J, Preface. In: Horder TJ, Witkowski JA, Wylie CC, eds., A History of Embryology Cambridge: Cambridge University Press, 1986: vii-viii.

    Google Scholar 

  58. Oyama S. Essentialism, women, and war: Protesting too much, protesting too little. Reprinted in Hull DL, Ruse M, eds., Philosophy of Biology. Oxford: Oxford University Press, 1998: 414–426.

    Google Scholar 

  59. Gray R. Death of the gene: Developmental systems strike back. In Griffiths PE, ed., Trees of Life. Dordrecht: Kluwer, 1992: 165–209.

    Google Scholar 

  60. Griffiths PE, Gray R. Developmental systems and evolutionary explanation. J Phil 1994; 91: 277–304.

    Google Scholar 

  61. Neumann-Held EM. The gene is dead-Long live the gene! Conceptualizing genes the constructionist way. In: Koslowski P, ed., Sociobiology and Bioeconomics: The Theory of Evolution in Biological and Economic Theory. Berlin: Springer-Verlag, 1999: 105–137.

    Google Scholar 

  62. Sarkar S. Biological information: A skeptical look at some central dogmas of molecular biology. In: Sarkar S, ed., The Philosophy and History of Molecular Biology: New Perspectives. Dordrecht: Kluwer, 1996: 187–231.

    Google Scholar 

  63. Mahner M, Bunge M. Foundations of Biophilosophy. Berlin: Springer-Verlag, 1997.

    Google Scholar 

  64. Goldsmith HH, Gottesman II, Lemery KS. Epigenetic approaches to developmental psychopathology. Dev Psychopathol 1997; 9: 365–387.

    Google Scholar 

  65. Lewontin RC. Human Diversity, 2nd ed. New York: Scientific American Library, 1995.

    Google Scholar 

  66. Lewontin RC. The dream of the human genome. NY Rev Books 1992; 28 May: 31–40.

    Google Scholar 

  67. Lewontin RC. Biology as Ideology: The Doctrine of DNA. Toronto: House of Anansi Press, 1991.

    Google Scholar 

  68. Lewontin RC. Gene, organism, and environment. In: Bendall DS, ed., Evolution from Molecules to Men. Cambridge: Cambridge University Press, 1983: 273–285.

    Google Scholar 

  69. Turkheimer E, Goldsmith HH, Gottesman II. Commentary [on 51]. Hum Dev 1995; 38: 142–153.

    Google Scholar 

  70. Gannett L. What's in a vause? The pragmatic dimensions of genetic rxplanations. Biol Phil 1999; 14: 349–374.

    Google Scholar 

  71. Schaffner, KF. Genes, behavior, and developmental emergentism: One process, indivisible? Phil Sci 1998; 65: 209–252.

    Google Scholar 

  72. Griffiths PE, Knight RD. What is the developmentalist challenge? Phil Sci 1998; 65: 253–258.

    Google Scholar 

  73. Farmer A, Owen MJ. Genomics: The next psychiatric revolution? Br J Psychiatry 1996; 169: 135–138.

    Google Scholar 

  74. Owen MJ, McGuffin P. The molecular genetics of schizophrenia. Br Med J 1992; 305: 664–665.

    Google Scholar 

  75. Tauber AI, Sarkar S. The ideology of the human genome project. J R Soc Med 1993; 86: 537–540.

    Google Scholar 

  76. Wimsatt WC. False models as means to truer theories. In Nitecki MH. Hoffman A, eds., Neutral Models in Biology. Oxford: Oxford University Press, 1987: 23–55.

    Google Scholar 

  77. Bodmer W, McKie R. The Book of Man: The Quest to Discover Our Genetic Heritage. Toronto: Viking Press, 1994.

    Google Scholar 

  78. Rose S. Lifelines: Biology Beyond Determinism. Oxford: Oxford University Press, 1997.

    Google Scholar 

  79. Billings PR, Beckwith J, Alper JS. The genetic analysis of human behavior: A new era? Soc Sci Med 1992; 35: 227–238.

    Google Scholar 

  80. Harris HW, Schaffner KF. Molecular Genetics, Reductionism, and Disease Concepts in Psychiatry. J Med Philos 1992; 17: 127–153.

    Google Scholar 

  81. Tsuang MT. Genetics, epidemiology, and the search for causes of schizophrenia. Am J Psychiatry 1994; 151: 3–6.

    Google Scholar 

  82. Nicol J. Sleuthing for medical clues. Maclean's 1999; 20 September: 48.

    Google Scholar 

  83. Moldin S. Genetics and mental disorders: Summary of research. Biol Psychiatry 1999; 45: 573–602.

    Google Scholar 

  84. Crow TJ, DeLisi LE. The chromosome workshops at the 5th international congress of psychiatric genetics-The weight of the evidence from genome scans. Psychiatr Genet 1998; 8: 59–61.

    Google Scholar 

  85. DeLisi LE, Crow TJ. Chromosome workshops 1998: Current state of psychiatric linkage. Am J Med Genet 1999; 88: 215–218.

    Google Scholar 

  86. Andreasen NC, Nopoulos P, O'Leary DS, et al. Defining the phenotype of schizophrenia: Cognitive dysmetria and its neural mechanisms. Biol Psychiatry 1999; 46: 908–920.

    Google Scholar 

  87. Andreasen NC, Carpenter WT Jr. Diagnosis and classification of schizophrenia. Schizophrenia Bull 1993; 19: 199–214.

    Google Scholar 

  88. Andreasen NC. The evolving concept of schizophrenia: From kraepelin to the present and future. Schizophrenoa Res 1997; 28: 105–109.

    Google Scholar 

  89. Meltzer HY. What is schizophrenia? Schizophrenia Bull 1982; 8: 433.

    Google Scholar 

  90. Young A. The Harmony of Illusions: Inventing Post-Traumatic Stress Disorder. Princeton: Princeton University Press, 1995.

    Google Scholar 

  91. Millon T. On the past and the future of DSM-III: Personal recollections and projections. In Millon T, Klerman GL, eds., Contemporary Directions in Psychopathology: Toward the DSM-IV. New York: Guilford Press, 1986: 29–70.

    Google Scholar 

  92. Bayer R, Spitzer RL. Neurosis, psychodynamics, and DSM-III. Arch Gen Psychiatry 1985; 42: 187–196.

    Google Scholar 

  93. Andreasen NC. The diagnosis of schizophrenia. Schizophrenia Bull 1987; 13: 9–22.

    Google Scholar 

  94. Sass LA. The Paradoxes of Delusion: Wittgenstein, Schreber, and the Schizophrenic Mind. Ithaca: Cornell University Press, 1994.

    Google Scholar 

  95. Lander ES. Splitting schizophrenia. Nature 1988; 336: 105–106.

    Google Scholar 

  96. Kendler KS, Karkowski LM, Walsh D. The structure of psychosis: Latent class analysis of probands from the roscommon family study. Arch Gen Psychiatry 1998; 55: 492–499.

    Google Scholar 

  97. Crow TJ. From Kraepelin to Kretschmer leavened by Schneider: The transition From categories of psychosis to dimensions of variation intrinsic to Homo sapiens. Arch Gen Psychiatry 1998; 55: 502–504.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Philosophy, McMaster University, Hamilton, Ontario, L8S 4K1, Canada

    Jason Scott Robert

Authors
  1. Jason Scott Robert
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Robert, J.S. Schizophrenia Epigenesis?. Theor Med Bioeth 21, 191–215 (2000). https://doi.org/10.1023/A:1009913618140

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1009913618140

Search

Navigation