126. Altered Complement and Coagulation Cascade in Age 11 Children Precedes to the Onset of Psychotic Disorder

Background: The identification of early biomarkers of psychotic disorder is important because early treatment is associated with improved outcome. In the current study, our objective was to identify peripheral protein biomarkers and underlying molecular alterations in children that predict the future development of psychotic disorder. Methods: The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective general population cohort, and a rich resource of demographic, environmental, and clinical data on the individuals involved. We studied a subsample of the cohort who participated in psychiatric assessments interviews at age 18, and who provided plasma samples at age 11. Proteomic profiling was used to identify and quantify the expression of plasma proteins in age 11 children who did (n = 37) or did not (n= 38) develop psychotic disorder at age 18. Results: Sixty plasma proteins were found to be differentially expressed (P < .05) in age 11 children with an outcome of psychotic disorder in comparison to healthy age-matched controls. Thirty-four proteins remained significant following correction for multiple comparisons, for which the combined expression levels predicted an outcome of psychotic disorder with >90% accuracy (ROC of 0.91). Pathway analysis of all dysregulated proteins implicated the complement and coagulation cascade as showing altered levels in children prior to the onset of psychotic disorder. A targeted proteomic approach was used to confirm this finding in a second ALSPAC age 11 cohort who did (n = 38) or did not (n = 66) report psychotic experiences, at age 18. Conclusion: We found that proteins involved in the Complement and Coagulation system are dysregulated in the blood during childhood long before the development of psychotic disorder. Although these findings need to be confirmed in independent and larger studies, future therapeutic strategies that target these processes in those at risk of developing psychotic disorder should be considered.