Hippocampal and cortical growth-associated protein-43 messenger RNA in schizophrenia.

Growth-associated protein-43 is involved in maturational and plasticity-associated processes, and changes in growth-associated protein-43 expression are a marker of altered plasticity following experimental and neuropathological lesions. Using in situ hybridization, we have investigated growth-associated protein-43 mRNA in the medial temporal lobe and cerebral cortex in 11 normal subjects and 11 matched subjects with schizophrenia, a disorder in which perturbed neurodevelopment and aberrant plasticity are implicated. In the schizophrenia group, growth-associated protein-43 messenger RNA was decreased in the medial temporal lobe, primary visual cortex and anterior cingulate gyrus, bur was unaltered in the superior temporal and dorsolateral prefrontal cortices. Correlations of growth-associated protein-43 messenger RNA signal between areas were stronger and more numerous in the schizophrenics than in the controls, suggesting a more global regulation of growth-associated protein-43 expression. Finally, the ratio of growth-associated protein-43 messenger RNA to synaptophysin messenger RNA-a putative index of the production of new synapses-was decreased in the medial temporal lobe in the schizophrenics. Our findings imply that neuronal plasticity as indexed by growth-associated protein-43 expression is impaired, and perhaps aberrantly regulated, in schizophrenia. The data support the emerging view that the disease pathophysiology is one which affects the hippocampal and cortical; circuitry and that the abnormalities are reflected in the altered expression of specific neuronal genes. (C) 1998 IBRO. Published by Elsevier Science Ltd.