It has been suggested that infection during perinatal life may lie at the etiological root of schizophrenia. It has thus been hypothesized that the origin of schizophrenia may lie either in direct fetal infection and/or in a generally increased familial susceptibility to infections, some of which may occur during pregnancy. We explored these 2 hypotheses by assessing maternal infection during pregnancy and maternal as well as paternal infection in general as predictors of schizophrenia in their offspring. We found a slightly increased risk to be associated with prenatal infection exposure. However, the effect of prenatal infection exposure was not statistically significantly different from the effect of infection exposure in general. Parental infection appeared to be associated with development of schizophrenia in adolescence and early adulthood. Our study does not exclude a specific effect of infection during fetal life; yet, it does suggest that schizophrenia is associated with an increased familial liability to develop severe infection.
In a landmark study, Mednick et al presented data that suggested that prenatal exposure to influenza infection during the second trimester was associated with schizophrenia illness later in life. Many studies have since tried to verify and expand this finding, though with mixed results. A recent meta-analysis by Selten et al concludes that evidence to support the maternal influenza hypothesis remains insufficient. Studies on the association between infection and schizophrenia may be grouped into ecological studies and studies of birth cohorts. A majority have used an ecological design and therefore lack information on individual exposure status as stated in a review by Brown et al. Some birth cohort studies have investigated the possible association between maternal infection during pregnancy and schizophrenia. A study following offspring of women examined serologically for rubella has related rubella to schizophrenia and related disorders in the offspring. Studies using stored sera from pregnant women have linked the presence of maternal antibodies to influenza A virus, herpes simplex virus type 2 (HSV-2), and the protozoan Toxoplasma Gondii  to the subsequent development of schizophrenia spectrum disorders. Mortensen et al using neonatal blood spots found an association with maternal IgG against T. Gondii and HSV-2. Although these studies measured maternal IgG antibodies against specific infections, they could not determine if the mother became infected during pregnancy. Despite numerous well performed studies linking congenital or neonatal viral infections to schizophrenia, the viral hypothesis remains compelling but is as yet unproven. New data continue to emerge linking viral infections to the etiopathogenesis of schizophrenia and the use of biomarkers of prenatal infections in rigorous epidemiological
by Philip R. Nielsen, Thomas M. Laursen, Preben B. Mortensen