Elevated maternal cytokine levels at birth and risk for psychosis in adult offspring

Background: Pregnancy and birth complications, particularly those associated with maternal inflammation and fetal hypoxia, are associated with increased risk for schizophrenia later in life. However, the molecular mechanisms underlying these associations are not fully delineated. This study sought to examine the effect of exposure to maternal inflammation on risk of developing psychosis in adulthood. Maternal serum levels of pro-inflammatory Th1 cytokines (IL-2, interferon gamma [IFN-γ], IL-12) and Th17 cytokines (IL-1b, IL-6, IL-8, tumor necrosis factor alpha [TNF-α], granulocyte macrophage colony stimulating factor [gm-csf]) and anti-inflammatory Th2 cytokines (IL-4, IL-5, and IL-13) and Treg cytokines (IL-10) were evaluated for association with later psychosis in the offspring. Methods: Subjects were 43 adults with psychoses and 43 matched controls followed from gestation as part of the Philadelphia cohort of the National Collaborative Perinatal Project. Adult symptoms of psychosis were assessed via medical records review and confirmed with a validation study. Archived maternal serum samples collected at the time of birth were analyzed for cytokine levels using a multiplex bead assay. Results: Individuals exposed to elevated maternal levels of anti-inflammatory Th2 cytokines (≥. 75th percentile) were significantly less likely to develop psychosis in adulthood. Conclusions: These results may suggest that increased maternal levels of anti-inflammatory cytokines during the perinatal period could protect against the development of psychosis.