M20. CYTOKINE LEVELS THROUGHOUT PREGNANCY AND RISK FOR PSYCHOSIS IN ADULT OFFSPRING: EARLY PREGNANCY MATTERS

BACKGROUND: Schizophrenia has been associated with pregnancy and birth complications, and fetal exposure to inflammation is thought to be a common underlying mechanism. However, it is unclear whether the risk associated with inflammation is specific to particular phases of pregnancy, as no prior studies have examined maternal serum samples across multiple assessments from the first trimester onward. This study examined differences in longitudinal patterns of maternal serum levels of TNFa, IL-1b, IL-5, IL-6, IL-8, IL-10, and IL-17a across pregnancy for offspring who were later ascertained as having a psychotic disorder diagnosis, non-psychotic siblings of these cases, and unrelated, non-psychotic individuals who served as controls. METHODS: Participants included 90 offspring, 79 siblings, and 273 matched controls from the Philadelphia cohort of the National Collaborative Perinatal Project. Psychotic disorder diagnoses in adulthood were assessed with review of medical records and were confirmed with a validation study. Cytokine levels were assessed using a multiplex bead assay in archived maternal serum samples collected across prenatal visits and birth. RESULTS: Levels of pro-inflammatory TNFa, IL-1b, and IL-6 were significantly higher in maternal serum of offspring who later developed psychosis relative to maternal serum of non-psychotic siblings and matched controls. These differences were maximal in first half of pregnancy (7–20 weeks), tapering to non-significant during the second half of pregnancy. DISCUSSION: These findings elucidate the importance of exposure to elevated maternal pro-inflammatory cytokine levels in early pregnancy to the etiology of psychosis.