Schizophrenia: the teratogenic antibody Hypothesis

  • P. Wright
  • P. Laing
  • P. T. Donaldson
  • R. M. Murray
Part of the Key Topics in Brain Research book series (KEYTOPICS)


Disease discordance of 50% in monozygotic twins implicates genetic and environmental factors in the aetiology of schizophrenia. Autoimmune diseases are HLA associated and are thought to occur when a genetically predisposed individual is exposed to an essential, probably viral, environmental trigger. We have reported an excess of autoimmune diseases in the first degree relatives of schizophrenic patients, an excess of second trimester influenza infections in the mothers of schizophrenic patients, and a deficiency of HLA DRB1*O4 alleles in the mothers of schizophrenic patients and in schizophrenic patients themselves. We have therefore hypothesised that maternal immunogenetic predisposition interacts with the influenza virus to cause neurodevelopmental lesions which manifest in adulthood as schizophrenia. Our work raises the possibility of an (immuno)genetic predisposition to schizophrenia at pedigree, maternal, and proband level.

Having a schizophrenic relative is the single most powerful risk factor for schizophrenia (Gottesman, 1991). However, disease discordance of about 50% in monozygotic twins (M2) both confirms the contribution of genes to the aetiology of schizophrenia and implicates non-genetic environmental factors (Gottesman, 1991; Walker et al., 1991; Torrey, 1992). One hypothesis that may encompass these genetic and environmental aetiological contributions suggests that schizophrenia occurs because of genetic susceptibility to an unidentified environmental agent. An increased frequency of autoimmune diseases has been found in the relatives of schizophrenic patients (MacSweeney et al., 1978; Ganguli et al., 1987; DeLisi et al., 1990 and we have reported an excess of both insulin dependent diabetes mellitus (IDDM) and of thyrotoxicosis in the first degree relatives of 101 psychotic patients when compared to 115 controls (Gilvarry et al, 1996), and an excess of IDDM (but not of thyrotoxicosis) in the relatives of 121 DSM-III-R schizophrenic patients (Wright et al, 1996a) when compared to controls. Given the apparent contributions of both genes and environmental factors to schizophrenia, these reports are of particular interest because autoimmune diseases are thought to occur when a genetically predisposed individual is exposed to an essential, probably viral, environmental trigger. Furthermore, disease discordance of about 50% in MZ twins has been reported for several autoimmune diseases (Knight et al, 1992).

In this paper we discuss how immunogene-viral interactions may explain some of the epidemiological features of schizophrenia and will review the evidence implicating prenatal influenza virus as one environmental aetiological factor. We also consider potential mechanisms by which influenza might increase risk for schizophrenia and propose a model — the teratogenic antibody hypothesis — which may explain a proportion of those cases of schizophrenia that appear to be related to prenatal influenza exposure.


Influenza Virus Schizophrenic Patient Prenatal Exposure Influenza Infection Swine Influenza 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag Wien 1999

Authors and Affiliations

  • P. Wright
    • 1
  • P. Laing
    • 2
  • P. T. Donaldson
    • 3
  • R. M. Murray
    • 1
  1. 1.Department of Psychological MedicineInstitute of Psychiatry and King’s College HospitalLondonUK
  2. 2.Peptide Therapeutics Group PLCCambridgeUK
  3. 3.Institute of Liver StudiesKing’s College HospitalLondonUK

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