Abstract
Schizophrenia (SCZ) is a polygenic severe mental illness. Genome-wide association studies (GWAS) have detected genomic variants associated with this psychiatric disorder and pathway analyses have indicated immune system and dopamine signaling as core components of risk in dorsolateral-prefrontal cortex (DLPFC) and hippocampus, but the mechanistic links remain unknown. The RasGRP1 gene, encoding for a guanine nucleotide exchange factor, is implicated in dopamine signaling and immune response. RasGRP1 has been identified as a candidate risk gene for SCZ and autoimmune disease, therefore representing a possible point of convergence between mechanisms involving the nervous and the immune system. Here, we investigated RasGRP1 mRNA and protein expression in post-mortem DLPFC and hippocampus of SCZ patients and healthy controls, along with RasGRP1 protein content in the serum of an independent cohort of SCZ patients and control subjects. Differences in RasGRP1 expression between SCZ patients and controls were detected both in DLPFC and peripheral blood of samples analyzed. Our results indicate RasGRP1 may mediate risk for SCZ by involving DLPFC and peripheral blood, thus encouraging further studies to explore its possible role as a biomarker of the disease and/or a target for new medication.
Highlights
Schizophrenia (SCZ) is a severe brain disorder affecting about 1% of the population worldwide
Evidence from Genome-wide association studies (GWAS) of immune system diseases, such as autoimmune thyroid disease, celiac disease, Crohn’s disease, inflammatory bowel disease, psoriasis, rheumatoid arthritis (RA), SjÖgren’s syndrome and systemic lupus erythematosus (SLE), indicates that, even at different levels of significance, these conditions are genetically correlated with SCZ [12,13]
Human dorsolateral-prefrontal cortex (DLPFC) and hippocampus samples were collected from post-mortem brains of non-psychiatric controls and SCZ patients (n = 20/brain region/clinical condition)
Summary
Schizophrenia (SCZ) is a severe brain disorder affecting about 1% of the population worldwide. Evidence from GWASs of immune system diseases, such as autoimmune thyroid disease, celiac disease, Crohn’s disease, inflammatory bowel disease, psoriasis, rheumatoid arthritis (RA), SjÖgren’s syndrome and systemic lupus erythematosus (SLE), indicates that, even at different levels of significance, these conditions are genetically correlated with SCZ [12,13]. This evidence suggests that molecular pathways subtending SCZ, and immune disorders are, at least in part, overlapping and that risk genes for SCZ may have a pleiotropic effect on risk for immune dysfunction [14]. SCZ patients and controls were detectable both in the brain and in peripheral blood of samples explored
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