Evidence for an Interaction Between Familial Liability and Prenatal Exposure to Infection in the Causation of Schizophrenia

Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
American Journal of Psychiatry (Impact Factor: 12.3). 07/2009; 166(9):1025-30. DOI: 10.1176/appi.ajp.2009.08010031
Source: PubMed


The authors sought to determine whether prenatal exposure to infection and a positive family history of psychotic disorders interact synergistically to increase the risk of later developing schizophrenia.
The authors linked two national registers, the Medical Birth Register and the Finnish Population Register, to identify all women in Helsinki who received hospital treatment during pregnancy for an upper urinary tract infection (N=9,596) between 1947 and 1990. The Finnish Hospital Discharge Register was used to ascertain psychiatric outcomes in adulthood of offspring exposed to infection prenatally. Family history of psychotic disorders was determined by linking the Hospital Discharge Register and the Population Register. The authors used an additive statistical interaction model to calculate the amount of biological synergism between positive family history and prenatal exposure to infection.
Prenatal exposure to infection did not significantly increase the risk of schizophrenia. However, the effect of prenatal exposure to pyelonephritis was five times greater in those who had a family history of psychosis compared to those who did not. The synergy analysis suggested that an estimated 38%-46% of the offspring who developed schizophrenia and had both prenatal exposure to infection and a positive family history of psychotic disorders did so as a result of the synergistic action of both risk factors.
These findings support a mechanism of gene-environment interaction in the causation of schizophrenia.

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Available from: Matti Huttunen, Oct 23, 2015
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    • "Schizophrenia is one of the most severe psychiatric disorders with worldwide lifetime prevalence approaching 1%, and characterized by psychotic features (delusions and hallucinations), disorganization, dysfunction in normal affective responses, and altered cognitive functions (Andreasen, 1995). Previous studies have implicated schizophrenia as an illness involved by interactions of one or more environmental insults with predisposing genetic susceptibility (Cannon et al., 2003; Caspi and Moffitt, 2006; Clarke et al., 2009). Among these environmental hazards, viral infection is one of the most widely accepted factors that could increase risk of future development of schizophrenia. "
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    • "Influenza has been the most widely studied pathogen in the MIA literature, because of its prevalence in the general population. Other studies have, however, revealed that less prevalent infections and viruses including bacterial infections (Clarke et al., 2009; Sorensen et al., 2009), bronchopneumonia (Brown et al., 2000), polio (Suvisaari et al., 1999; Cahill et al., 2002), herpes simplex virus (Buka et al., 2001, 2008; Babulas et al., 2006), rubella (Brown et al., 2000, 2001), and toxoplasma gondii (Brown et al., 2005; Mortensen et al., 2007) are also associated with increased risk for schizophrenia in the offspring of those infected. This common effect across various infections suggests that a specific infection or virus does not, in and of itself, increase the risk of schizophrenia. "
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    • "These patients also performed significantly worse in neuropsychological measures of psychomotor speed, executive functioning and verbal memory.115,116) Prenatal infection and subsequent inflammatory attack on a background of genetic liability serves to further increase the risk of developing SCZ, consistent with the idea that genetic factors are necessary for inflammation to affect in utero brain development.119) "
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