SMAD4 protein is decreased in the dorsolateral prefrontal and anterior cingulate cortices in schizophrenia

Signal transduction through the mothers against decapentaplegic (SMAD) is a family of signal transduction factors that mediate signalling of the transforming growth factor B (TGFB)-superfamily of cell regulatory proteins. A recent transcriptomic analysis of post-mortem, cortical tissue from subjects with schizophrenia found decreased mRNA expression of SMAD2 and SMAD4 in the dorsolateral prefrontal cortex (DLPFC) associated with the disorder. To expand this initial finding, we sought to determine whether SMAD2 and SMAD4 protein were also altered in the cortex from subjects with schizophrenia.

Western blotting was used to measure SMAD2 and SMAD4 protein levels in DLPFC and anterior cingulate cortex (ACC) taken post-mortem from subjects with schizophrenia (n = 20) and matched control (n = 20) subjects.

Compared to controls, levels of SMAD4 were 25% lower in the DLPFC and 38% lower in the ACC from subjects with schizophrenia. By contrast, SMAD2 levels were not altered in either DLPFC or ACC.

Our finding of lower SMAD4 protein in the cortex suggests there are likely to be abnormalities in cortical TGFB-superfamily signalling in schizophrenia.