Reduced GAP-43 mRNA in dorsolateral prefrontal cortex of patients with schizophrenia

Schizophrenia has been associated with anatomical and functional abnormalit ies of the dorsolateral prefrontal cortex (DLPFC), which may reflect abnorm al connections of DLPFC neurons. We measured mRNA levels of growth-associat ed protein (GAP-43), a peptide linked to the modifiability of neuronal conn ections, in post-mortem brain tissue from two cohorts of patients with schi zophrenia and controls. Using the RNase protection assay (RPA), we found a significant reduction in GAP-43 mRNA in the DLPFC, but not in the hippocamp us, of patients with schizophrenia. With in situ hybridization histo chemis try (ISHH), performed on a separate cohort, we confirmed the reduction of G AP-43 mRNA in the DLPFC of patients with schizophrenia. We detected reduced GAP-43 mRNA per neuron in layers III, V and VI of patients with schizophre nia compared with normal controls and patients with bipolar disorder. Thus, glutamate neurons in DLPFC of schizophrenic patients may synthesize less G AP-43, which could reflect fewer and/or less modifiable connections than th ose in normal human brain, and which may be consistent with the deficits of prefrontal cortical function that characterize schizophrenia.