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Background Prenatal infection is associated with brain structural and functional abnormalities, and may increase risk for psychosis through a direct effect on neurodevelopment. Proinflammatory immune response may be a common mechanism through which various infections exert their harmful effect, but studies of prenatal maternal inflammatory markers and offspring neurodevelopment are scarce. We examined the associations of maternal prenatal C-reactive protein (CRP) levels with psychosis risk factors in adolescent offspring including markers of neurodevelopment and cannabis use. Methods This study used a longitudinal birth cohort, the Northern Finland Birth Cohort 1986 (NFBC 1986), followed up to age 16 years (n=6,985/9,432, 76% follow-up). CRP was measured in maternal sera collected in pregnancy. In offspring, school performance was measured at age 7 and 16y; psychotic experiences and cannabis use was measured at age 16. Controlling for offspring sex, maternal education level, maternal body mass index during pregnancy, smoking during pregnancy and alcohol use during pregnancy using regression analysis, we tested associations of CRP with offspring measures. We also tested for mediation, specifically if adolescent cannabis use mediated the associations between maternal CRP and offspring psychotic experiences and school performance. Results Based on data from a minimum of 4,153 participants, after controlling for offspring sex, maternal education level, maternal body mass index during pregnancy, smoking during pregnancy and alcohol use during pregnancy, maternal CRP was associated with adolescent neurodevelopmental markers, including psychotic experiences (odds ratio=1.13, 95% CI=1.00–1.29) and academic performance at age 16 years (beta=0.063, SE=0.013, 95% CI=0.037–0.089). Maternal CRP was also associated with adolescent cannabis use (odds ratio=1.27, 95% CI=1.11–1.46). Cannabis use appeared to mediate a small amount of the associations between maternal CRP and both psychotic experiences and academic performance. Discussion These results support a neurodevelopmental role for maternal prenatal infection and offspring psychosis but also suggest an indirect effect through increasing risk of exposure to cannabis. Maternal infection and immune activation may impact on brain circuitry involved in impulsivity, increasing behaviours such as cannabis use that are separately associated with psychosis. The results of this study give clues regarding the mechanism of the maternal inflammation – psychosis association and add to our understanding of the complex neurodevelopmental processes predating psychosis.

schizophrenia bulletin

O10.1. MATERNAL PRENATAL C-REACTIVE PROTEIN, NEURODEVELOPMENT AND OTHER RISK FACTORS FOR PSYCHOSIS IN ADOLESCENT OFFSPRING IN THE NORTHERN FINLAND BIRTH COHORT 1986