ABSTRACT
This study aimed to test whether a dysregulation of gene expression may be the underlying cause of previously reported elevated levels of inflammatory cytokines in veterans with schizophrenia. We performed a genome-wide expression analysis in peripheral blood mononuclear cells from veterans with schizophrenia and controls, and our results show that 167 genes and putative loci were differently expressed between groups. These genes were enriched primarily for pathways related to inflammatory mechanisms and formed networks related to cell death and survival, immune cell trafficking, among others, which is in line with previous reports and further validates the inflammatory hypothesis of schizophrenia.
Subject(s)
Cytokines/genetics , Cytokines/metabolism , Gene Expression/physiology , Leukocytes, Mononuclear/metabolism , Schizophrenia , Adult , Female , Genome-Wide Association Study , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Schizophrenia/genetics , Schizophrenia/immunology , Schizophrenia/pathology , United States , VeteransABSTRACT
Pro-inflammatory cytokines have been consistently reported to be elevated in schizophrenia patients. However, it is not known whether cytokines influence the presentation of psychotic symptoms. To address this issue, we evaluated the relationship between levels of inflammatory molecules and psychopathological parameters in patients with schizophrenia. We hypothesized that severity of symptoms would correlate with increased levels of inflammatory cytokines. Serum samples from 47 veterans with a diagnosis of schizophrenia and 20 healthy controls were tested for levels of 38 cytokines/chemokines involved in regulation of immune/inflammatory reactions using a Millipore multiplex bead array in a Luminex 100 system. We found significantly increased levels of GRO, MCP-1, MDC, and sCD40L, and significantly decreased levels of IFN-γ, IL-2, IL-12p70, and IL-17, in schizophrenia patients compared to controls. In addition, we observed positive correlations between levels of cytokines and the Positive and Negative Symptoms Scale (PANSS) scores in subjects with schizophrenia for G-CSF, IL-1ß, IL1ra, IL-3, IL-6, IL-9, IL-10, sCD40L and TNF-ß. Pathway analyses showed these cytokines to be part of the IL17 pathway. Using principal component analyses, we found the factor that included these cytokines and IL-17 to be associated with positive, general and total PANSS scores. These results suggest that alterations in this pathway may play a role in development of psychotic symptoms in schizophrenia.
