ALTERED LEVELS OF THE SYNAPTOSOMAL ASSOCIATED PROTEIN SNAP-25 IN SCHIZOPHRENIA

Background: identifying brain changes in schizophrenia has been a majo r research focus for many years. Although impressive gains have been m ade in neuroimaging and brain electrophysiology, molecular and cellula r markers of schizophrenia have lagged. There are no consistent bioche mical markers for schizophrenia pathophysiology and none that reflect treatment course, Methods: Samples were obtained from 25 postmortem sc hizophrenic brains and 31 nonschizophrenic controls, These samples wer e processed, and the synaptosomal fraction was isolated. Ten microgram s of protein from each of these samples was solubilized in a sodium do decylsulfate sample buffer and separated on 10% (wt/vol) polyacrylamid e gels. Monoclonal antibody (SMI-81) was incubated with the blots and, using quantitative Western blotting we measured the relative amounts of SNAP-25 in these samples. Results: We report altered levels of SNAP -25 in both the inferior temporal cortex (Brodmann area 20) and prefro ntal association cortex (Brodmann areas 9 and 10) in postmortem brains of patients with schizophrenia relative to nonschizophrenic controls. Normal levels of SNAP-25 are noted in schizophrenics in area 17, decr eased levels in areas 10 and 20, and an elevated level in area 9, Conc lusions: These data support cytoarchitectural observations that the ce rebral cortex of schizophrenic patients has extensive pathology. The d ata presented here, along with data on other brain-specific proteins, indicate a complicated molecular adaptation to the causative factors o f schizophrenia. (C) 1998 Society of Biological Psychiatry.