Alterations in synaptic proteins and their encoding mRNAs in prefrontal cortex in schizophrenia: a possible neurochemical basis for 'hypofrontality'

An impairment of prefrontal cortical functioning in schizophrenia ('hypofro ntality') has been suggested by clinical, neuroimaging, and postmortem brai n tissue studies, We used Western immunoblot and Northern hybridization ana lyses of postmortem brain tissue obtained from 14 schizophrenic patients an d 12 control patients of similar ages to measure tissue levels of synaptoph ysin (a structural synaptic vesicle protein) and of SNAP-25 (a 25-kDa presy naptic protein), and their encoding mRNAs, in Brodmann's area in of prefron tal cortex. There were significant decreases in tissue levels of both of th ese proteins in prefrontal cortex of schizophrenic patients relative to con trols, In contrast, tissue levels for the mRNAs encoding these proteins wer e not decreased in schizophrenic patients. Subsequent labeling of the same Western immunoblots showed no difference in tissue levels of glial fibrilla ry acidic protein (GFAP) in schizophrenic and control patients. Similarly, subsequent hybridization of the same Northern hybridization membranes showe d no difference in tissue levels of GFAP mRNA or of 28S rRNA in schizophren ic and control patients, These alterations in tissue levels of synaptophysi n and SNAP-25 are consistent with the idea that the clinically observed 'hy pofrontality' of schizophrenia arises from abnormalities of synaptic number or structural integrity in prefrontal cortex.