Abstract
BackgroundThe identification of early biomarkers of psychotic disorder is important because early treatment is associated with improved outcome. We have previously shown that altered complement and coagulation pathway associated proteins are associated pathway with psychotic disorder at age 18. In the current study we test the hypothesis that altered complement pathway proteins are associated with persisting psychotic experiences from age 11 to age 18.MethodsThe 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 assessment interviews at age 11 and 18, and who provided plasma samples at age 11. Semi-targeted proteomic profiling was used to specifically assess the complement pathway proteins in age 11 children who experienced psychotic experiences (but not disorder) at age 11 and age 18 (n=39) compared to age 11 children who only experienced psychotic experiences at age 11.Results11 of 34 proteins assessed were significantly differentially expressed at p<0.05 and of these 8 remained significant following correction for multiple comparisons. Protein changes were in keeping with increased proteins expression of most complement pathway proteins. Several protein changes represented specific replications of the changes observed in age 11 samples prior to psychotic disorder at age 18, namely increased plasminogen, complement factor H, and complement factor 1r.DiscussionOur findings implicate the blood complement system in the persistence of psychotic experiences from age 11 to age 18. Considering that psychotic experiences are predictive of many psychiatric disorders our findings implicate the complement system not just in psychotic disorders, but more broadly in the vulnerability to a range of adult psychiatric disorders.
Highlights
Concurrent SymposiaS53 are microdomains comprised of about 1000 unique proteins that are interacting with one another via specialized multipotent scaffolding molecule
In the post-genomic era, proteomics has emerged as a powerful tool to unravel biomarker candidates and to understand human diseases from the molecular point of view
More than 95% of Postsynaptic density-95 (PSD-95) expression is localized to excitatory synapses, and it is the most abundant scaffolding protein within the postsynaptic density
Summary
S53 are microdomains comprised of about 1000 unique proteins that are interacting with one another via specialized multipotent scaffolding molecule. To investigate excitatory postsynaptic protein hubs in schizophrenia, we assessed the PSD-95 protein interactome from brain tissue of subjects with schizophrenia and controls. Methods: Human brain tissue from fifteen subjects with schizophrenia and fifteen control subjects from the DLPFC was processed for affinity purification of PSD-95 protein complexes. We subtracted any non- captured peptides identified by our IgG control studies that were performed in parallel to PSD-95 affinity purification. Data were normalized within each of the mass spec runs to the most intense PSD-95 peptide. Results: Preliminary analyses indicate changes in the PSD-95 interactome consistent with diminished NMDA receptor signaling complex activity in schizophrenia, with lower levels of NMDA-subtype glutamate receptor subunits, as well as protein kinases associated with postsynaptic signaling in this complex. Mariana Fioramonte*,1, Daniel Martins-De-Souza1 1University of Campinas (UNICAMP)
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