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What risk factors tell us about the causes of schizophrenia and related psychoses

  • Published: September 2000
  • Volume 2, pages 378–385, (2000)
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What risk factors tell us about the causes of schizophrenia and related psychoses
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  • Jane Kelly MBBS, MRCPsych1 &
  • Robin M. Murray DSC, MD, FRCPsych1 
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  • 12 Citations

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Abstract

Genetic, epidemiologic, and molecular studies concur that liability to schizophrenia is transmitted through the inheritance of a number of genes of relatively small effect, some of which are shared with other psychoses. Each of these susceptibility genes causes minor deviations that are relatively innocent in themselves, for example, increased lateral ventricular volume, schizotypal personality, or subtle cognitive difficulties. However, when an individual is unlucky enough to inherit several of these traits, their cumulative effect, often compounded by environmental hazards, propels that person over a threshold for the expression of frank psychosis. Early environmental risk factors for schizophrenia include urban and winter birth, fetal malnutrition and hypoxia, and possibly prenatal viral infections; these early hazards have only a modest risk-increasing effect, and operate in the context of genetic risk. Preschizophrenic children are more likely to have minor psychomotor and cognitive problems; low IQ has a linear relationship with risk for schizophrenia. However, schizophrenia is not simply a neurodevelopmental disorder, because risk factors have been identified that have their effects proximal to the onset of psychosis: drug abuse, immigrant status, and social adversity and isolation. Both genetic and environmental risk factors appear to operate across diagnostic categories and therefore support a dimensional model of psychosis.

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References and Recommended Reading

  1. McDonald C, Murray R: Early and late environmental risk factors for schizophrenia. Brain Res Rev 2000, 31:130–137.

    Article  PubMed  CAS  Google Scholar 

  2. Murray R, Fearon P: The developmental ‘risk factor’ model of schizophrenia. J Psychiatr Res 1999, 33:497–499.

    Article  PubMed  CAS  Google Scholar 

  3. Jones P, Cannon M: The new epidemiology of schizophrenia. Psychiatr Clin N Am 1998, 21:1–25.

    Article  CAS  Google Scholar 

  4. Andreasen NC: Understanding the causes of schizophrenia. New Engl J Med 1999, 340:645–647.

    Article  PubMed  CAS  Google Scholar 

  5. Cannon T, Kaprio J, Lonnqvist J, et al.: The genetic epidemiology of schizophrenia in a Finnish twin cohort. Arch Gen Psychiatry 1998, 55:67–74.

    Article  PubMed  CAS  Google Scholar 

  6. Cardno A, Marshall J, Coid B, et al.: Heritability estimates for psychotic disorders. Arch Gen Psychiatry 1999, 56:162–168.

    Article  PubMed  CAS  Google Scholar 

  7. Cardno AG, Jones LA, Murphy KL, et al.: Dimensions of psychosis in affected sibling pairs. Schiz Bull 1999, 25:841–850.

    CAS  Google Scholar 

  8. Owen M: Searching for susceptibility genes in schizophrenia. In Search for the Causes of Schizophrenia IV edited by W F Gattaz WF, Hafner H. Berlin: Springer Verlag; 1999:169–180.

    Google Scholar 

  9. Gottesman I, Shields J: Schizophrenia and Genetics. London: Academic Press; 1972.

    Google Scholar 

  10. Freeman H: Schizophrenia and city residence. Br J of Psychiatry 1994, 164(supp 23):39–50.

    Google Scholar 

  11. Lewis G, David A, Andreasson S, et al.: Schizophrenia and city life. Lancet 1992, 340:137–140.

    Article  PubMed  CAS  Google Scholar 

  12. Mortensen P, Pedersen C, Westergaard T, et al.: Effects of family history and place and season of birth on the risk of schizophrenia. N Engl J Med 1999, 340:603–608. Large, comprehensive epidemiologic study able to determine relative risks, population attributable fractions and interactions between risk factors. Correspondence in N Engl J Med 1999, 341:370–372.

    Article  PubMed  CAS  Google Scholar 

  13. Marcelis M, Takei N, Van Os J: Urbanization and risk for schizophrenia: does the effect operate before or around the time of illness onset? Psychol Med 1999, 29:1197–1203.

    Article  PubMed  CAS  Google Scholar 

  14. Bradbury TN, Miller GA: Season of birth in schizophrenia: a review of the evidence, methodology and etiology. Psychol Bull 1985, 98:569–594.

    Article  PubMed  CAS  Google Scholar 

  15. McGrath J, Welham J, Pemberton M: Month of birth, hemisphere of birth and schizophrenia. Br J Psychiatry 1995, 167:783–785.

    PubMed  CAS  Google Scholar 

  16. Izumoto Y, Inoue S, Yasuda N: Schizophrenia and the influenza epidemics of 1957 in Japan. Biol Psychiatry 1999, 46:119–124.

    Article  PubMed  CAS  Google Scholar 

  17. Erlenmeyer-Kimling L, Folnegovic Z, Hrabak-Zerjavic V, et al.: Schizophrenia and prenatal exposure to the 1957 A2 influenza epidemic in Croatia. Am J Psychiatry 1994, 151:1496–1498.

    PubMed  CAS  Google Scholar 

  18. Susser E, Lin S, Brown A, et al.: No relation between risk of schizophrenia and prenatal exposure to influenza in Holland. Am J Psychiatry 1994, 151:922–924.

    PubMed  CAS  Google Scholar 

  19. Seltern J, Brown A, Moons K, et al.: Prenatal exposure to the 1957 influenza pandemic and non-affective psychosis in The Netherlands. Schizophr Res 1999, 38:85–91.

    Article  Google Scholar 

  20. Wright P, Takei N, Rifkin L, et al.: Maternal Influenza, obstetric complications and schizophrenia. Am J Psychiatry 1997, 154:292–293.

    Google Scholar 

  21. Westergaard T, Mortensen P, Pedersen C, et al.: Exposure to prenatal and childhood infections and the risk of schizophrenia. Arch Gen Psychiatry 1999, 56:993–998.

    Article  PubMed  CAS  Google Scholar 

  22. Takei N, Sham P, O’Callaghan E, et al.: Schizophrenia increased risk associated with winter and city birth. J Epidemiol Commun Health 1995, 49:106–107.

    CAS  Google Scholar 

  23. O’Callaghan E, Cotter D, Colgan K, et al.: Confinement of winter birth excess in schizophrenia to the urban born and its gender specificity. Br J Psychiatry 1995, 166:51–54.

    PubMed  CAS  Google Scholar 

  24. Verdoux H, Takei N, Cassou R, et al.: Seasonality of birth in schizophrenia: the effect of regional population density. Schizophr Res 1997, 23:175–180.

    Article  PubMed  CAS  Google Scholar 

  25. Brown A, Cohen P, Greenwald S, et al.: Non-affective psychosis after prenatal exposure to rubella. Am J Psychiatry 2000, 157:438–443.

    Article  PubMed  CAS  Google Scholar 

  26. Susser E, Neugebauer R, Hoek H, et al.: Schizophrenia after prenatal famine: further evidence. Arch Gen Psychiatry 1996, 53:25–31.

    PubMed  CAS  Google Scholar 

  27. Susser E, Hoek H, Brown A: Neurodevelopmental disorders after prenatal famine. Am J Epidemiol 1998, 147:213–216.

    PubMed  CAS  Google Scholar 

  28. Verdoux H, Geddes J, Takei N, et al.: Obstetric complications and age of onset in schizophrenia: an international collaborative meta-analysis of individual patient data. Am J Psychiatry 1997, 154:1220–1227.

    PubMed  CAS  Google Scholar 

  29. Rosso I, Cannon T, Huttemen T, et al.: Obstetric risk factors for early onset schizophrenia in a Finnish birth cohort. Am J Psychiatry 2000, 157:801–807.

    Article  PubMed  CAS  Google Scholar 

  30. Geddes JR, Verdoux H, Takei N, et al.: Schizophrenia and complications of pregnancy and labor: an individual patient data meta-analysis. Schizophr Bull 1999, 25:413–423.

    PubMed  CAS  Google Scholar 

  31. Zornberg G, Buka S, Tsuang M, et al.: Hypoxic-ischemic-related fetal/neonatal complications and risk of schizophrenia and other non-affective psychoses: a 19-year long study. Am J Psychiatry 2000, 157:196–202.

    Article  PubMed  CAS  Google Scholar 

  32. Kendell R, McInneny K, Juszczak E, et al.: Obstetric complications and schizophrenia. Br J Psychiatry 2000, 176:516–523.

    Article  PubMed  CAS  Google Scholar 

  33. Kendell RE, Juszczak E, Cole SK: Obstetric complications and schizophrenia: A case-control study based on standardised obstetric records. Br J Psychiatry 1996, 168:556–561.

    PubMed  CAS  Google Scholar 

  34. Jones P, Rantakallio P, Hartikainen A, et al.: Schizophrenia as a long-term outcome of pregnancy, delivery, and perinatal complications: a 28-year follow-up of the 1966 north Finland general population birth cohort. Am J Psychiatry 1998, 155:355–364.

    PubMed  CAS  Google Scholar 

  35. Hultman C, Sparen P, Takei N, et al.: Prenatal and perinatal risk factors for schizophrenia, affective psychosis, and reactive psychosis of early onset: a case control study. Br Med J 1999, 318:421–426. Large study of pre- and perinatal risk factors for early-onset psychosis including interaction with gender.

    CAS  Google Scholar 

  36. Dalman C, Allebeck P, Cullberg J, et al.: Obstetric complications and the risk of schizophrenia. Arch Gen Psychiatry 1999, 56:234–240.

    Article  PubMed  CAS  Google Scholar 

  37. Jones P, Rodgers B, Murray R, Marmot M: Child developmental risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 1994, 344:1398–1402.

    Article  PubMed  CAS  Google Scholar 

  38. Fish B: Infants at risk of schizophrenia: sequelae of a genetic neurointegrative defect. Arch Gen Psychiatry 1992, 49:221–235.

    PubMed  CAS  Google Scholar 

  39. Marcus J, Hans SL, Auerbach JG, et al.: Children at risk for schizophrenia: the Jerusalem infant development study. Arch Gen Psychiatry 1993, 50:797–809.

    PubMed  CAS  Google Scholar 

  40. Hollis C: Child and adolescent (juvenile onset) schizophrenia. A case control study of pre-morbid developmental impairments. Br J Psychiatry 1995, 166:489–495.

    PubMed  CAS  Google Scholar 

  41. Nicholson R, Lenane M, Singaracharlu S, et al.: Premorbid speech and language impairments in childhood-onset schizophrenia: associations with risk factors. Am J Psychiatry 2000, 157:794–800.

    Article  Google Scholar 

  42. Cannon M, Jones P, Huttunen M, et al.: School performance in Finnish children and later development of schizophrenia. Arch Gen Psychiatry 1999, l56:457–463. Large population-based case-control study pointing to developmental abnormalities in middle childhood.

    Article  Google Scholar 

  43. Walker E, Lewine RJ: Prediction of adult-onset schizophrenia from childhood home movies of the patients. Am J Psychiatry 1994, 147:1052–1056.

    Google Scholar 

  44. Davidson M, Reichenberg A, Rabinowitz J, et al.: Behavioural and Intellectual Markers for schizophrenia in apparently healthy male adolescents. Am J Psychiatry 1999, 156:1328–1335. Evidence of developmental problems in preschizophrenic adolescents.

    PubMed  CAS  Google Scholar 

  45. David A, Malberg A, Brandt L, et al.: IQ and risk for schizophrenia: a population-based cohort study. Psychol Med 1997, 27:1311–1323. Demonstrates linear relationship between IQ and risk for schizophrenia.

    Article  PubMed  CAS  Google Scholar 

  46. Chua SE, McKenna PJ: Schizophrenia—a brain disease? A critical review of structural and functional cerebral abnormality in the disorder. Br J of Psychiatry 1995, 166:563–582.

    CAS  Google Scholar 

  47. Wright IC, Rabe-Hesketh S, Woodruff P, et al.: Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiatry 2000, 157:16–25.

    PubMed  CAS  Google Scholar 

  48. Jones PB, Harvey I, Lewis SW, et al.: Cerebral ventricle dimensions as risk factors for schizophrenia and affective psychosis: an epidemiological approach to analysis. Psychol Med 1994, 24:995–1011.

    PubMed  CAS  Google Scholar 

  49. Sharma T, Lancaster E, Lewis S, et al.: Lack of normal pattern of cerebral asymmetry in familial schizophrenic patients and their relatives. Schizophr Res 1999, 40:111–120.

    Article  PubMed  CAS  Google Scholar 

  50. Stefanis N, Frangou S, Yakeley J, et al.: Hippocampal volume reduction in schizophrenia: effects of genetic risk and pregnancy and birth complications. Biol Psychiatry 1999, 46:607–702.

    Article  Google Scholar 

  51. McNeil T, Cantor-Graae E, Weinberger D, et al.: Relationship of obstetric complications and difference in size of brain structures in monozygotic twin pairs discordant for schizophrenia. Am J Psychiatry 2000, 157:208–212.

    Article  Google Scholar 

  52. Leonard C, Kuldau J, Breier J, et al.: Cumulative effect of anatomical risk factors for schizophrenia: an MRI study. Biol Psychiatry 1999, 46:374–382.

    Article  PubMed  CAS  Google Scholar 

  53. Van Os J, Marcelis M: The ecogenetics of schizophrenia. Schizophr Res 1998, 32:127–135.

    Article  PubMed  Google Scholar 

  54. Cannon TD, Hollister JM, Bearden CE, et al.: A prospective cohort study of genetic and perinatal influences in schizophrenia. Arch Gen Psychiatry 1997, 24:248.

    Google Scholar 

  55. Fearon P, Cotter D, Murray R: Is the association between obstetric complications and schizophrenia mediated by glutamatergic excitotoxic damage in the fetal/ neonatal brain? In Psychopharmacology of Schizophrenia. Edited by Reveley MA, Deakin JF. London: Chapman and Hall; 1999.

    Google Scholar 

  56. Tienari P: Interaction between genetic vulnerability and family environment: The Finnish adoptive family study of schizophrenia. Acta Psychiatrica Scand 1991, 84:460–465.

    CAS  Google Scholar 

  57. Tienari P, Wynne L, Laksy K, et al.: Finnish Adoptive Family Study. Acta Psychiatric Scand 2000, 101:433–443.

    Article  CAS  Google Scholar 

  58. Rosenthal D, Wender P, Kety S, et al.: The adopted-away offspring of schizophrenics. Am J Psychiatry 1971, 128:307–311.

    PubMed  CAS  Google Scholar 

  59. Mirsky AF, Silberman EK, Latz A, et al.: Adult outcomes of high-risk children: differential effects of town and kibbutz rearing. Schizophr Bull 1985, 11:150–156.

    PubMed  CAS  Google Scholar 

  60. King M, Coker E, Leavey G, et al.: Incidence of psychotic illness in London: a comparison of ethnic groups. BMJ 1994, 309:1115–1119.

    PubMed  CAS  Google Scholar 

  61. Thomas CS, Stone K, Osborn M, et al.: Psychiatric morbidity and compulsory admission among UK born Europeans, Afro-Caribbeans and Asians in central Manchester. Br J Psychiatry 1993, 163:91–99.

    PubMed  CAS  Google Scholar 

  62. Seltern JP, Sijben N: First admission rate for schizophrenia in immigrants to The Netherlands: the Dutch National Register. Soc Psychiatry Psychiatr Epidemiol 1994, 29:71–72.

    Google Scholar 

  63. Odegaard O: Emigration and insanity: a study of mental disease among Norwegian born population in Minnesota. Acta Psychiatr. Neurol Scand 1932, (Supp 4).

  64. Harrison G, Owens D, Holten A, et al.: A prospective study of severe mental disorder in Afro-Caribbean patients. Psychol Med 1988, 18:643–657.

    PubMed  CAS  Google Scholar 

  65. Van Os J, Castle DJ, Takei N, et al.: Psychotic illness in ethnic minorities: clarification from the 1991 census. Psychol Med 1996, 26:203–208.

    Article  Google Scholar 

  66. Hickling W, McKenzie K, Mullen R, et al.: A Jamaican psychiatrist evaluates diagnoses at a London hospital. Br J Psychiatry 1999, 175:283–285.

    PubMed  CAS  Google Scholar 

  67. McGuire P, Jones P, Harvey M: Morbid risk of schizophrenia in relatives of patients with cannabis-associated psychosis. Schizophrenia Res 1995, 15:277–281.

    Article  CAS  Google Scholar 

  68. Glover G: Why is there a high rate of schizophrenia in British Caribbeans? Br J Hosp Med 1989, 42:48–51.

    PubMed  CAS  Google Scholar 

  69. Harrison G: Searching for the causes of schizophrenia: the role of migrant studies. Schizophr Bull 1990, 16:663–671.

    PubMed  CAS  Google Scholar 

  70. Hutchinson G, Takei N, Bhugra T, et al.: Increased rate of psychosis among African-Caribbeans in Britain is not due to an excess of pregnancy and birth complications. Br J of Psychiatry 1997, 171:145–147.

    CAS  Google Scholar 

  71. Wessely S, Castle D, Der R, et al.: Schizophrenia and Afro-Caribbeans. A case-control study. Br J Psychiatry 1991, 159:795–801.

    PubMed  CAS  Google Scholar 

  72. Hutchinson G, Takei N, Fahy TA, et al.: Morbid risk of schizophrenia in first-degree relatives of white and African-Caribbean patients with psychosis. Br J Psychiatry 1996, 169:776–780. Suggested cohort-specific risk factors.

    PubMed  CAS  Google Scholar 

  73. Sugarman P, Crauford D: Schizophrenia in the Afro-Caribbean community. Br J Psychiatry 1994, 164:474–480.

    PubMed  CAS  Google Scholar 

  74. Malmberg A, Lewis G, David A, et al.: Premorbid adjustment and personality in people with schizophrenia. Br J Psychiatry 1998, 172:308–313.

    PubMed  CAS  Google Scholar 

  75. Van Os J, Driessen G, Gunther N, et al.: Neighbourhood variation in incidence of schizophrenia. Evidence for personenvironment interaction. Br J Psychiatry 2000, 176:243–248.

    Article  PubMed  Google Scholar 

  76. Jablensky A, Cole SW: Is the earlier age at onset of schizophrenia in males a confounded finding? Results from a crosscultural investigation. Br J Psychiatry 1997, 170:234–240.

    PubMed  CAS  Google Scholar 

  77. Bebbington P, Wilkins S, Jones P, et al.: Life events and psychosis. Initial results from the Camberwell Collaborative Psychosis Study. Br J Psychiatry 1993, 162:72–79.

    PubMed  CAS  Google Scholar 

  78. Ventura J, Nuechterlein KH, Lukoff D, Hardesty JP: A prospective study of stressful life events and schizophrenic relapse. J Abnorm Psychol 1989, 98:407–411.

    Article  PubMed  CAS  Google Scholar 

  79. Malla A, Cortese L, Shaw TS, et al.: Life events and relapse in schizophrenia: a one year prospective study. Soc Psychiatry Psychiatr Epidemiol 1990, 25:221–224.

    PubMed  CAS  Google Scholar 

  80. Andreasson S, Allebeck P, Engstrom A, et al.: Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet 1987, 2:1483–1486.

    Article  PubMed  CAS  Google Scholar 

  81. Murray RM, O’Callaghan E: The congenital and adult-onset psychoses: Kraepelin lost, Kraepelin found. In Concepts of mental disorder a continuing debate. Edited by Kerr A, McClelland H. London: Gaskell; 1991:48–65.

    Google Scholar 

  82. Murray RM, O’Callaghan E, Castle DJ, et al.: A neurodevelopmental approach to the classification of schizophrenia. Schizophr Bull 1992, 18:319–332.

    PubMed  CAS  Google Scholar 

  83. Castle DJ, Sham PC, Wessely S, et al.: The subtyping of schizophrenia in men and women: a latent class analysis. Psychol Med 1994, 24:41–51.

    PubMed  CAS  Google Scholar 

  84. Sham PC, Castle DJ, Wessely S, et al.: Further exploration of a latent class typology of schizophrenia. Schizophr Res 1998, 20:105–115.

    Article  Google Scholar 

  85. Done DJ, Crow TJ, Johnstone EC, et al.: Childhood antecedents of schizophrenia and affective illness: social adjustment at ages 7 and 11. BMJ 1994, 309:699–703.

    PubMed  CAS  Google Scholar 

  86. Van Os J, Lewis G, Jones P, et al.: Developmental precursors of affective illness in a general population birth cohort. Arch Gen Psychiatry 1997, 54:625–632.

    PubMed  Google Scholar 

  87. Van Os J, Jones P, Sham P, et al.: Risk factors for onset and persistence of psychosis. Soc Psychiatry Psychiatr Epidemiol 1998, 33:596–605.

    Article  PubMed  Google Scholar 

  88. McGorry PD, Bell RC, Dudgeon PL, et al.: The dimensional structure of first episode psychosis: an exploratory factor analysis. Psychol Med 1998, 28:935–947.

    Article  PubMed  CAS  Google Scholar 

  89. Kitamura T, Okazaki Y, Fujinawa A, et al.: Symptoms of psychoses. A factor-analytic study. Br J Psychiatry 1995, 166:236–240.

    Article  PubMed  CAS  Google Scholar 

  90. Van Os J, Fahy TA, Jones P, et al.: Psychopathological syndromes in the functional psychoses: associations with course and outcome. Psychol Med 1996, 26:161–176.

    Article  PubMed  Google Scholar 

  91. Van Os J, Gilvarry C, Bale R, et al.: A comparison of the utility of dimensional and categorical representations of Group. Psychol Med 1999, 29:595–606. Demonstrates the application of a dimensional model of psychosis.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Psychological Medicine, Institute of Psychiatry, SE5 8AF, De Crespigny Park, London, England

    Jane Kelly MBBS, MRCPsych & Robin M. Murray DSC, MD, FRCPsych

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  1. Jane Kelly MBBS, MRCPsych
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  2. Robin M. Murray DSC, MD, FRCPsych
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Kelly, J., Murray, R.M. What risk factors tell us about the causes of schizophrenia and related psychoses. Curr Psychiatry Rep 2, 378–385 (2000). https://doi.org/10.1007/s11920-000-0019-1

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  • Issue Date: September 2000

  • DOI: https://doi.org/10.1007/s11920-000-0019-1

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Keywords

  • Influenza
  • Schizophrenia
  • Environmental Risk Factor
  • Birth Complication
  • Affective Psychosis
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