Evidence for an interaction between familial liability and prenatal exposure to infection in the causation of schizophrenia.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These findings support a mechanism of gene-environment interaction in the causation of schizophrenia.
Clarke
Mary C
MC
Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 9, Ireland. maryclarke@rcsi.ie
Tanskanen
Antti
A
Huttunen
Matti
M
Whittaker
John C
JC
Cannon
Mary
M
D000328:Adult; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D005190:Family / Q000523:psychology*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007239:Infections / Q000453:epidemiology*; D008297:Male; D018811:Maternal Exposure / Q000706:statistics & numerical data*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology*; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology; D015995:Prevalence; D011704:Pyelonephritis / Q000453:epidemiology; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics
D005819:Genetic Markers