Cortical expression of the RAPGEF1 gene in schizophrenia: investigating regional differences and suicide

Abstract

Rap guanine nucleotide exchange factor 1 (RAPGEF1) is involved in cell adhesion and neuronal migration. Previously we found lower RAPGEF1 mRNA levels in Brodmann's area (BA) 9 in subjects with schizophrenia compared to controls. This study aimed to determine whether RAPGEF1 expression was altered in other brain regions implicated in schizophrenia and whether this was associated with suicide. Using qPCR, we measured the levels of RAPGEF1 in post-mortem BA 8 and 44 from 27 subjects with schizophrenia and 26 non-psychiatric control subjects. To address the effect of antipsychotic treatments, Rapgef1 mRNA levels were measured in the cortex from rats treated with typical antipsychotic drugs. There was no difference in RAPGEF1 normalised relative expression levels in BA 8 or 44. However, in BA 8, schizophrenia subjects had higher raw Ct RAPGEF1 levels compared to controls. There were higher RAPGEF1 levels in suicide completers compared to non-suicide schizophrenia subjects in BA 8. Rapgef1 expression levels in the rat cortex did not vary with antipsychotic treatment. Our findings suggest changes in RAPGEF1 expression may be limited to the dorsolateral prefrontal cortex from subjects with schizophrenia. Further investigation of the function of RAPGEF1 may lead to a greater understanding of the pathophysiology of schizophrenia.