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14-09-2009 | Mental health | Article

Prenatal infection and family history synergistically raise schizophrenia risk


Free abstract

MedWire News: Prenatal exposure to infection appears to work synergistically with a family history of psychosis to increase the risk for developing schizophrenia in later life, a team of European researchers has discovered.

While the majority of studies have found an association between prenatal exposure to wide range of infections and an increased risk for schizophrenia, there have been some negative findings. Previous investigations have attempted to incorporate genetic liability into assessment of the effect of prenatal infection exposure but such studies have been hampered by methodological issues.

Mary Clarke, from the Royal College of Surgeons in Ireland, in Dublin, and colleagues identified all women in Helsinki who received hospital treatment during pregnancy for an upper urinary tract infection between 1947 and 1990 by linking the Finnish Population Register and the Medical Birth Register.

In order to determine the adult psychiatric outcomes of offspring exposed to prenatal infection, the team used the Finnish Hospital Discharge Register, while the family history of psychotic disorders was determined by linking the Hospital Discharge Register with the Population Register.

The sample group, which consisted of 9596 individuals who were in gestation when their mothers were hospitalized for pyelonephritis, was compared with 13,808 of their unexposed siblings. Overall, the prevalence of a family history of psychosis was 6.4%.

Prenatal exposure to infection did not significantly increase the risk for developing schizophrenia or broadly defined psychotic disorder, although the increased risk for schizophrenia was of borderline significance, at an odds ratio of 1.48. A family history of psychosis significantly increased the risk for both schizophrenia and broadly defined psychotic disorder, at odds ratios of 2.99 and 3.29, respectively.

Interestingly, the effect of prenatal exposure to infection was significantly greater in individuals who had a family history of psychosis compared with those without such a history, at a risk difference of 0.51% versus 0.10%. Analysis revealed that 38–46% of the individuals who developed schizophrenia did so as a result of prenatal infection exposure and family history of psychosis working synergistically.

“We found an additive effect of having a positive family history such that, when coupled with prenatal exposure to infection, the risk is significantly increased relative to those who were exposed to infection but are not at increased familial risk,” the team says in the American Journal of Psychiatry.

“In those who are genetically vulnerable to psychotic disorder, the risk difference between those exposed and those unexposed to infection was five times larger than the risk difference between the exposed and the unexposed among those without genetic vulnerability.”

MedWire ( is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

By Liam Davenport

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