Madness Explained

by Richard P. Bental

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  35. For an excellently accessible description of these new techniques, see Barondes, Mood Genes, op. cit.

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  37. J. A. Egeland, D. S. Gerhard, D. L. Pauls, J. N. Sussex, K. K. Kidd, C. R. Allen, A. M. Hostetter and D. E. Housman (1987). ‘Bipolar affective disorder linked to DNA markers on chromosome 11’, Nature, 325: 783–7.

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  41. R. Sherrington, J. Brynjolfsson, H. Pertursson, M. Potter, K. Dudleston, B. Barraclough, J. Wasmuth, M. Dobbs and H. G. Gurling (1988) ‘Localization of a susceptibility locus for schizophrenia on chromosome 5’, Nature, 336: 164–7.

  42. J. L. Kennedy, L. A. Giuffra, H. W. Moises, L. I. Cavalli-Sforza, A. J. Pakstis, J. R. Kidd, C. M. Castiglione, L. Wetterberg and K. K. Kidd (1988) ‘Evidence against linkage of schizophrenia to markers on chromosome 5 in a northern Swedish pedigree’, Nature, 336: 167–70.

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  44. S. D. Detera-Wadleigh, L. R. Goldin, R. Sherrington et al. (1989) ‘Exclusion of linkage to 5q11–13 in families with schizophrenia and other psychiatric disorders’, Nature, 340: 391–3.

  45. G. Turecki, G. A. Rouleau, J. J. Mari and K. Morgan (1996) ‘A systematic evaluation of linkage studies in bipolar disorder’, Acta Psychiatrica Scandinavica, 93: 317–26; S. G. Simpson and J. R. DePaulo (1998) ‘Genetics’, in P. J. Goodnick (ed.), Mania: Clinical and Research Perspectives. Washington, DC: American Psychiatric Association.

  46. The dopamine hypothesis, discussed in Chapter 4, was proposed when it was discovered that anti-psychotic drugs block dopamine receptors. There are five known types of dopamine receptor, and the genes for all five types are known. Reviewing the molecular evidence, Petter Portin and Y.O. Alanen of the University of Turku in Finland (‘A critical review of genetic studies of schizophrenia. II: Molecular genetic studies’, Acta Psychiatrica Scandinavica, 95: 73–80, 1997) have concluded that, ‘On the whole, it seems that molecular genetic studies lend only minor support to the dopamine theory of schizophrenia.’

  47. D. B. Wildenauer, S. G. Schwab, W. Maier and S. D. Detera-Wadleigh (1999) ‘Do schizophrenia and affective disorder share susceptibility genes?’Schizophrenia Research, 39: 107–11.

  48. T. J. Crow (1997) ‘Current status of linkage for schizophrenia: polygenes of vanishingly small effect or multiple false positives?’ American Journal of Medical Genetics (Neuropsychiatric Genetics), 74: 99–103; Portin and Alanen, ‘A critical review of genetic studies of schizophrenia, II, op. cit.

  49. Crow, ‘Current status of linkage for schizophrenia’, op. cit.

  50. Schizophrenia Linkage Collaborative Group for Chromosomes 3 and 6a (1996) ‘Additional support for schizophrenia linkage on chromosomes 6 and 8: a multicenter study’, American Journal of Medical Genetics (Neuropsychiatric Genetics), 67: 580–94.

  51. L. E. DeLisi, S. H. Shaw, T. J. Crow, G. Shields, A. B. Smith, V. W. Larach, N. Wellman, J. Loftus, B. Nanthakumar, K. Razi, J. Stewart, M. Comazzi, A. Vita, T. Heffner and R. Sherrington (2002) ‘A genome-wide scan for linkage to chromosomal regions in 382 sibling pairs with schizophrenia or schizoaffective disorder’, American Journal of Psychiatry, 159: 803–12.

  52. S. O. Moldin (1997) ‘The maddening hunt for madness genes’, Nature Genetics, 17: 127–9.

  53. K. K. Kidd (1997) ‘Can we find genes for schizophrenia?’ American Journal of Medical Genetics (Neuropsychiatric Genetics), 74: 104–11; E. Rall (1998) ‘Commentary: where are the genes specifying mental illness?’ Journal of Nervous and Mental Disease, 186: 722–3.

  54. A. Serretti, F. Macciardi, M. Catalano, L. Bellodi and E. Smeraldi (1999) ‘Genetic variants of dopamine receptor D4 and psychopathology’, Schizophrenia Bulletin, 25: 609–18.

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  56. Consistent with this conclusion, a recent study of Irish families with a ‘high density’ of schizophrenia found six chromosomal regions associated with psychosis, but found that very few families were ‘positive’ with respect to more than one region. See R. E. Straub, C. J. MacLean, Y. Ma, B. T. Webb, M. V. Myakishev, C. Harris-Kerr, B. Wormley, H. Sadek, B. Kadambi, F. A. O’Neill, D. Walsh and K. S. Kendler (2002) ‘Genome-wide scans of three independent sets of 90 Irish multiplex schizophrenia families and follow-up of selected regions in all families provides evidence for multiple susceptibility genes’, Molecular Psychiatry, 7: 542–59.

  57. I. Feinberg (1997) ‘Schizophrenia as an emergent disorder of late brain maturation’, in Keshavan and Murray (eds.), Neurodevelopment and Adult Psycho-pathology, op. cit.

  58. P. R. Huttenlocher (1979) ‘Synaptic density in human frontal cortex – developmental changes and effects of aging’, Brain Research, 163: 195–205; P. R. Hutten-locher (1990) ‘Morphometric study of human cerebral cortex development’, Neuropsychologia, 517–27.

  59. G. Edelman (1989) Neural Darwinism: The Theory of Neuronal Group Selection. Oxford: Oxford University Press.

  60. N. Davies, A. Russell, P. Jones and R. M. Murray (1998) ‘Which characteristics of schizophrenia predate psychosis?’ Journal of Psychiatric Research, 32: 121–31.

  61. Feinberg, ‘Schizophrenia and late maturational brain changes’, op. cit.; R. E. Hoffman and T. H. McGlashan (1993) ‘Parallel distributed processing and the emergence of schizophrenic symptoms’, Schizophrenia Bulletin, 19: 257–61.

  62. M. Davidson, A. Reichenberg, J. Rabinowitz, M. Weiser, Z. Kaplan and M. Mark (1999) ‘Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents’, American Journal of Psychiatry, 156: 1328–35.

  63. E. F. Walker (1994) ‘Neurodevelopmental precursors of schizophrenia’, in A. S. David and J. C. Cutting (eds.), The Neuropsychology of Schizophrenia. Hove: Erlbaum.

  64. E. F. Walker, K. E. Grimes, D. M. Davis and A. J. Smith (1993) ‘Childhood precursors of schizophrenia: facial expressions of emotion’, American Journal of Psychiatry, 150: 1654–60.

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  66. M. Cannon, E. Walsh, C. Hollis, M. Kargin, E. Taylor, R. M. Murray and P. B. Jones (2001) ‘Predictors of later schizophrenia and affective psychosis among attendees at a child psychiatry department’, British Journal of Psychiatry, 178: 420–6.

  67. S. A. Mednick and F. Schulsinger (1965) ‘A longitudinal study of children with a high risk for schizophrenia: a preliminary report’, in S. Vandenberg (ed.), Methods and Goals in Human Behavior Genetics. New York: Academic Press.

  68. L. Erlenmeyer-Kimling and B. Cornblatt (1987) ‘The New York High-Risk Project: a follow-up report’, Schizophrenia Bulletin, 13: 451–63.

  69. J. Marcus, S. L. Hans, S. Nagler, J. G. Aurbach, A. F. Mirsky and A. Aubrey (1987) ‘Review of the NIMH Israeli Kibbutz–City Study and the Jerusalem Infant Development Study’, Schizophrenia Bulletin, 13: 425–39.

  70. P. H. Venables (1990) ‘Longitudinal research on schizophrenia’, in Bentall (ed.), Reconstructing Schizophrenia, op. cit.

  71. T. D. Cannon, S. A. Mednick and J. Parnas (1990) ‘Two pathways to schizophrenia in children at risk’, in L. Robins and M. Rutter (eds.), Straight and Devious Pathways from Childhood to Adulthood. Cambridge: Cambridge University Press.

  72. L. Erlenmeyer-Kimling, B. Cornblatt, A. S. Bassett, S. O. Moldin, U. Hilldoff-Adamo and S. Roberts (1990) ‘High-risk children in adolescence and young adulthood: course of global adjustment’, in Robins and Rutter (eds.), Straight and Devious Pathways, op. cit.

  73. L. Erlenmeyer-Kimling, U. H. Adamo, D. Rock, S. A. Roberts, A. S. Bassett, E. Squires-Wheeler, B. A. Cornblatt, J. Endicott, S. Pape and I. I. Gottesman (1997) ‘The New York High-Risk Project: prevalence and comorbidity of axis-I disorders in offspring of schizophrenic parents at 25-year follow-up’, Archives of General Psychiatry, 54: 1096–102.

  74. J. R. Asarnow (1988) ‘Children at risk for schizophrenia: converging lines of evidence’, Schizophrenia Bulletin, 14: 613–31.

  75. C. Hollis and E. Taylor (1997) ‘Schizophrenia: a critique from the developmental psychopathology perspective’, in Keshavan and Murray (eds.), Neurodevelopment and Adult Psychopathology, op. cit.

  76. Cannon, Mednick and Parnas, ‘Two pathways to schizophrenia’, op. cit.

  77. R. H. Dworkin, B. A. Cornblatt, R. Friedmann, L. M. Kaplansky, J. A. Lewis, A. Rinalsi, C. Shilliday and L. Erlenmeyer-Kimling (1993) ‘Childhood precursors of affective vs social deficits in adolescents at risk for schizophrenia’, Schizophrenia Bulletin, 19: 563–76; L. R. Freedman, D. Rock, S. A. Roberts, B. A. Cornblatt and L. Erlenmeyer-Kimling (1998) ‘The New York High-Risk Project: attention, anhedonia and social outcome’, Schizophrenia Research, 30: 1–9.

  78. P. B. Jones and D. J. Done (1997) ‘From birth to onset: a developmental perspective of schizophrenia in two national birth cohorts’, in Keshavan and Murray (eds.), Neurodevelopment and Adult Psychopathology, op. cit.

  79. E. Frenkel, S. Kugelmass, M. Nathan and L. J. Ingraham (1995) ‘Locus of control and mental health in adolescence and adulthood’, Schizophrenia Bulletin, 21: 219–26.

  80. S. A. Mednick (1970) ‘Breakdown in individuals at high risk of schizophrenia: possible predisposing perinatal factors’, Mental Hygiene, 54: 50–63.

  81. S. W. Lewis, M. J. Owen and R. M. Murray (1989) ‘Obstetric complications and schizophrenia: methodology and mechanisms’, in S. C. Schulz and C. A. Tamming (eds.), Schizophrenia: A Scientific Focus. New York: Oxford University Press; S. L. Buka, M. T. Tsuang and L. P. Lipsitt (1993) ‘Pregnancy/delivery complications and psychiatric diagnosis: a prospective study’, Archives of General Psychiatry, 50: 151–6.

  82. D. J. Done, E. C. Johnstone, C. D. Frith, J. Golding, P. M. Shepard and T. J. Crow (1991) ‘Complications of pregnancy and delivery in relation to psychosis in adult life: data from the British Perinatal Mortality Survey’, British Medical Journal, 302: 1576–80.

  83. E. O’Callaghan, T. Gibson, H. A. Colohan, P. Buckley, D. G. Walshe, C. Larkin and J. L. Waddington (1992) ‘Risk of schizophrenia in adults born after obstetric complications and their association with early onset of illness: a controlled study’, British Medical Journal, 305: 1256–9.

  84. D. Cotter, C. Larkin, J. L. Waddington and E. O’Callaghan (1996) ‘Season of birth in schizophrenia: clue or cul-de-sac?’, in J. L. Waddington and P. F. Buckley (eds.), The Neurodevelopmental Basis for Schizophrenia. New York: Chapman Hall, pp. 17–30; E. F. Torrey, J. Miller, R. Rawlings and R. H. Yolken (1997) ‘Seasonality of births in schizophrenia and bipolar disorder: a review of the literature’, Schizophrenia Research, 28: 1–38.

  85. E. F. Torrey and R. H. Yolken (1995) ‘Could schizophrenia be a viral zoonosis transmitted from house cats?’ Schizophrenia Bulletin, 21: 167–77.

  86. S. Mednick, R. A. Machon, M. O. Huttenen and D. Bonnett (1988) ‘Adult schizophrenia following prenatal exposure to an influenza epidemic’, Archives of General Psychiatry, 45: 188–92; P. C. Sham, E. O’Callaghan, N. Takei, G. K. Murray, E. H. Hare and R. M. Murray (1992) ‘Increased risk of schizophrenia following prenatal exposure to influenza’, British Journal of Psychiatry, 160: 461–6.

  87. T. J. Crow and D. J. Done (1992) ‘Prenatal exposure to influenza does not cause schizophrenia’, British Journal of Psychiatry, 161: 390–5; L. Erlenmeyer-Kimling, Z. Folnegovic, V. Hrabak-Zerjavic, B. Borcic, V. Folnegovic-Smale and E. Susser (1994) ‘Schizophrenia and prenatal exposure to the 1957 A2 influenza epidemic’, American Journal of Psychiatry, 151: 1496–8; J.-P. C. J. Selten and J. P. J. Slaets (1994) ‘Second trimester exposure to 1957 A2 influenza epidemic is not a risk factor for schizophrenia’, Schizophrenia Research, 11: 95; E. Susser, S. P. Lin, A. S. Brown, L. H. Lumey and L. Erlenmeyer-Kimling (1994) ‘No relation between risk of schizophrenia and prenatal exposure to influenza in Holland’, American Journal of Psychiatry, 151: 922–4.

  88. N. Takei, P. C. Sham, E. O’Callaghan, G. Glover and R. M. Murray (1995) ‘Schizophrenia: increased risk associated with winter and city birth: a case-control study in 12 regions within England and Wales’, Journal of Epidemiology and Community Health, 49: 106–7; H. Verdoux, N. Takei, R. Cassoude Saint Mathurin, R. M. Murray and M. L. Bourgeois (1997) ‘Seasonality of birth in schizophrenia: the effect of regional population density’, Schizophrenia Research, 23: 175–80.

  89. E. O’Callaghan, D. Cotter, K. Colgan and C. Larkin (1995) ‘Confinement of winter birth excess in schizophrenia to the urban-born and its gender specificity’, British Journal of Psychiatry, 166: 51–4.

  90. P. B. Mortensen, C. B. Pedersen, T. Westergaard, J. Wohlfahrt, H. Ewald, O. Mors, P. K. Andersen and M. Melbye (1999) ‘Effects of family history and place and season of birth on the risk of schizophrenia’, New England Journal of Medicine, 340: 603–8.

  91. Cotter et al., ‘Season of birth in schizophrenia’, op. cit.

  92. E. S. Susser and S. P. Lin (1992) ‘Schizophrenia after prenatal exposure to the Dutch hunger winter of 1944–1945’, Archives of General Psychiatry, 49: 983–8.

  93. J. McGrath and R. Murray (1995) ‘Risk factors for schizophrenia: from conception to birth’, in S. R. Hirsch and D. R. Weinberger (eds.), Schizophrenia. Oxford: Blackwell, pp. 187–205.

  94. ibid.

  95. C. M. Hultman, P. Sparen, N. Takei, R. M. Murray and S. Cnattingius (1999) ‘Prenatal and perinatal risk factors for schizophrenia, affective psychosis, and reactive psychosis of early onset: case control study’, British Medical Journal, 318: 421–6.

  96. J. B. Lohr and H. S. Bracha (1989) ‘Can schizophrenia be related to prenatal exposure to alcohol? Some speculations’, Schizophrenia Bulletin, 15: 595–603.

  97. H. A. Nasrallah (1997) ‘Neurodevelopment and affective disorders’, in Keshavan and Murray (eds.), Neurodevelopment and Adult Psychopathology, op. cit.

  98. J. Worland, R. Edenhart-Pepe, D. G. Weeks and P. M. Koren (1984) ‘Cognitive evaluation of children at risk: IQ, differentiation and egocentricity’, in N. F. Watt, E. J. Anthony, L. C. Wynne and J. E. Rolf (eds.), Children at Risk of Schizophrenia: A Longitudinal Perspectiv
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  99. J. J. van Os, P. Jones, G. Lewis, M. Wadsworth and R. M. Murray (1996) ‘Evidence for similar developmental precursors of chronic affective illness and schizophrenia in a general population birth cohort’, Archives of General Psychiatry, 54: 625–31.

  100. M. Cannon, P. Jones, C. Gilvarry, L. Rifkin, K. McKenzie, A. Foerster and R. M. Murray (1997) ‘Premorbid social functioning in schizophrenia and bipolar disorder: similarities and differences’, American Journal of Psychiatry, 154: 1544–50.

  101. Torrey et al., ‘Seasonality of births in schizophrenia and bipolar disorder’, op. cit.

  102. Nasrallah, ‘Neurodevelopment and affective disorders’, op. cit.

  103. A. S. Brown, J. van Os, C. Driessens, H. W. Hoek and E. S. Susser (2000) ‘Further evidence of relation between prenatal famine and major affective disorder’, American Journal of Psychiatry, 157: 190–5.