sk for schizophrenia.
In the first study, lead author Vicki Babulas and her Columbia colleagues searched for a connection between infections of the reproductive tract and schizophrenia in a sampling of mothers and their (now adult) children, in a birth cohort in northern California. Of the 7,794 offspring in the study, 71 were diagnosed with schizophrenia spectrum disorders. To determine the frequency of maternal infection, the researchers reviewed the mothers’ medical records for physician documentation of any of eight diagnoses, including endometritis, cervicitis, pelvic inflammatory disease, vaginitis, gonorrhea, syphilis, condylomata, or venereal disease during four pregnancy intervals—periconception and first, second, or third trimester.
Their results show that when the mother was exposed during the periconceptional period (from 30 days before the last menstrual period to 30 days after), the rate ratio for schizophrenia in the offspring was 5.03 (95 percent CI 2.00-12.64, p = .001), compared to unexposed pregnancies and adjusted for maternal race, education, age, and mental illness. The incidence of rates of schizophrenia did not differ between the offspring of exposed versus unexposed mothers at any other time during pregnancy.
Additional, larger studies will be needed to confirm these findings and clarify which of the many infectious agents involved contribute most to the prenatal risk identified in this study. But if the results are replicated, it opens the possibility that treating and preventing STDs before and during pregnancy could have an immediate impact on the children of infected mothers. The authors write, “It is conceivable that a reduction in the incidence of schizophrenia may be brought about by readily available pharmacotherapeutic and other public health measures.”
Effects of in utero cytokines depend on time of exposure
Infection of mothers might affect development of their babies via changes in both maternal and fetal cytokine levels. To look directly at the effect of maternal cytokines on fetal brain development, dual first authors of the second paper, Urs Meyer and Myriel Nyffeler used a mouse model of acute inflammation during pregnancy that results in behavioral deficits in the offspring (Shi et al., 2003; Meyer et al., 2005). In this model, injecting pregnant mice with a synthetic analog of double-stranded RNA (polyI:C) elicits a strong but transient inflammatory response, and allows studies on the effects on offspring through postnatal life.
By dosing at two different gestational stages, the investigators found distinct patterns of psychopathological outcomes, cytokine production, and brain neuropathology as a result of the timing of inflammation. When they treated with polyI:C at gestational day 9 (thought to be in the vicinity of the first-to-second trimester transition in humans: Kaufman, MH  The atlas of mouse development. London: Academic), the offspring showed significantly reduced exploratory behavior in an open field test as young adolescents. Offspring of mothers who were dosed at day 17 (equivalent to human second-to-third trimester transition) also showed a decrease in exploratory behavior in an open field, but it was much smaller and not statistically significant. The later-treated animals did show significant behavioral changes by a different measure, a reversal-of-choice task, where they took longer to learn the new choice. This perseverative behavior is proposed to model the lack of behavioral flexibility seen in schizophrenia and several other disorders, including autism and obsessive-compulsive disorder.
The neuropathological correlates of these behavioral changes were different in the offspring from earlier or later-treated mouse dams. Gross brain morphology was unaltered, but a closer look showed that the mice that were exposed on P9, and thus experienced inflammation at mid-gestation, had reduced reelin-positive cells in the hippocampus. The mice that experienced inflammation later showed reductions in reelin-expressing cells that were not as severe. Both groups had a los