ABNORMALITIES OF WNT SIGNALING IN SCHIZOPHRENIA - EVIDENCE FOR NEURODEVELOPMENTAL ABNORMALITY

THE Wnt signalling pathway is central to normal brain development in v ertebrates and invertebrates and mediates cell fate determination, cel l adhesion and cell proliferation. However, its relevance to disorders of cerebral development in man is untested. We evaluated the potentia l involvement of the Wnt signalling pathway in schizophrenia, a disord er of neurodevelopment origin in which alterations in neuronal laminat ion and orientation have been described. Using immunohistochemistry an d semi-quantitative rating scales, we examined the distribution of two components of the Wnt signalling pathway, beta-catenin and gamma-cate nin in the hippocampus and subiculum of 12 schizophrenic (DSMIIR crite ria) and 14 control subjects. Both catenins were distributed as intran euronal diffuse and/or ring shaped forms. The diffuse staining of both forms catenin were reduced in the CA3 and beta-catenin was also reduc ed in the CA4 hippocampal subregion among schizophrenic subjects. Thes e alternations may represent the basis of the developmental brain abno rmalities found in schizophrenia and would have functionally important consequences in the adult. (C) 1998 Rapid Science Ltd.