HIPPOCAMPAL AND CORTICAL GROWTH-ASSOCIATED PROTEIN-43 MESSENGER-RNA IN SCHIZOPHRENIA

Growth-associated protein-43 is involved in maturational and plasticit y-associated processes, and changes in growth-associated protein-43 ex pression are a marker of altered plasticity following experimental and neuropathological lesions. Using in situ hybridization, we have inves tigated 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 abe rrant plasticity are implicated. In the schizophrenia group, growth-as sociated protein-43 messenger RNA was decreased in the medial temporal lobe, primary visual cortex and anterior cingulate gyrus, bur was una ltered in the superior temporal and dorsolateral prefrontal cortices. Correlations of growth-associated protein-43 messenger RNA signal betw een areas were stronger and more numerous in the schizophrenics than i n the controls, suggesting a more global regulation of growth-associat ed protein-43 expression. Finally, the ratio of growth-associated prot ein-43 messenger RNA to synaptophysin messenger RNA-a putative index o f the production of new synapses-was decreased in the medial temporal lobe in the schizophrenics. Our findings imply that neuronal plasticit y as indexed by growth-associated protein-43 expression is impaired, a nd perhaps aberrantly regulated, in schizophrenia. The data support th e 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) 1 998 IBRO. Published by Elsevier Science Ltd.