Monocyte activation detected prior to a diagnosis of schizophrenia in the US Military New Onset Psychosis Project (MNOPP)

Abstract

Low-grade inflammation is present in some cases of schizophrenia, particularly in the early stages of this disorder. The inflammation source is not known but may be the result of dysbiotic processes occurring in the gut. We examined peripheral biomarkers of bacterial translocation, soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP), and of general inflammation, C-reactive protein (CRP), in a unique, pre-onset study of schizophrenia. This sample was composed of 80 case-control matched pairs of US military service members from whom blood samples were obtained at time of entry to service, before a psychiatric diagnosis was made. Elevated levels of sCD14 in individuals who were subsequently diagnosed with schizophrenia generated odds ratios of 1.22 for association with disease (p<0.02). Conversely, LBP levels for those who developed schizophrenia were unchanged or very marginally decreased compared to controls (p=0.06). No significant changes were found for CRP in schizophrenia compared with their matched controls. This diversity of patterns suggests that a dysregulated immune system is present prior to a diagnosis of schizophrenia. In particular, sCD14 elevation and discordant LBP decrease in cases support a more generalized monocyte activation rather than a specific translocation of gut bacteria into circulation. The corresponding absence of general inflammation as measured by CRP may indicate that this monocyte activation or related immune dysfunction precedes the early inflammatory stage frequently evident in schizophrenia.