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Increased Expression of Activity-Dependent Genes in Cerebellar Glutamatergic Neurons of Patients With Schizophrenia

OBJECTIVE: The purpose of this study was to evaluate the functional state of glutamatergic neurons in the cerebellar cortex of patients with schizophrenia. METHOD: The authors measured messenger ribonucleic acid (mRNA) levels of three activity-dependent genes expressed by glutamatergic neurons in the cerebellar cortex (GAP-43, BDNF, and GABA_A- subunit) in the tissues of 14 patients with schizophrenia and 14 matched nonpsychiatric comparison subjects. Since its level of expression does not change in response to neuronal activity, gamma-aminobutyric acid_A-6 subunit mRNA was used as a control. RESULTS: The levels of GAP-43 and BDNF mRNAs were significantly elevated in patients with schizophrenia, and a similar finding was observed for GABA_A- mRNA. In contrast, the levels of the GABA_A–6 subunit mRNA, which is expressed in cerebellar granule cells in an activity-independent manner, did not differ from comparison subjects. CONCLUSIONS: These results suggest that glutamatergic neurons may be hyperactive in the cerebellar cortices of patients with schizophrenia.

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Am J Psychiatry 2006 163: A62. [Full Text] [PDF]

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