Abnormalities of Wnt signalling in schizophrenia--evidence for neurodevelopmental abnormality.

The Wnt signalling pathway is central to normal brain development in vertebrates and invertebrates and mediates cell fate determination, cell adhesion and cell proliferation. However, its relevance to disorders of cerebral development in man is untested. We evaluated the potential involvement of the Wnt signalling pathway in schizophrenia, a disorder of neurodevelopment origin in which alterations in neuronal lamination and orientation have been described. Using immunohistochemistry and semi-quantitative rating scales, we examined the distribution of two components of the Wnt signalling pathway, beta-catenin and gamma-catenin in the hippocampus and subiculum of 12 schizophrenic (DSMIIR criteria) and 14 control subjects. Both catenins were distributed as intraneuronal diffuse and/or ring shaped forms. The diffuse staining of both forms catenin were reduced in the CA3 and beta-catenin was also reduced in the CA4 hippocampal subregion among schizophrenic subjects. These alternations may represent the basis of the developmental brain abnormalities found in schizophrenia and would have functionally important consequences in the adult.