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

Mol Psychiatry. 1999 Jan;4(1):39-45. doi: 10.1038/


An impairment of prefrontal cortical functioning in schizophrenia ('hypofrontality') has been suggested by clinical, neuroimaging, and postmortem brain tissue studies. We used Western immunoblot and Northern hybridization analyses of postmortem brain tissue obtained from 14 schizophrenic patients and 12 control patients of similar ages to measure tissue levels of synaptophysin (a structural synaptic vesicle protein) and of SNAP-25 (a 25-kDa presynaptic protein), and their encoding mRNAs, in Brodmann's area 10 of prefrontal cortex. There were significant decreases in tissue levels of both of these proteins in prefrontal cortex of schizophrenic patients relative to controls. In contrast, tissue levels for the mRNAs encoding these proteins were not decreased in schizophrenic patients. Subsequent labeling of the same Western immunoblots showed no difference in tissue levels of glial fibrillary acidic protein (GFAP) in schizophrenic and control patients. Similarly, subsequent hybridization of the same Northern hybridization membranes showed no difference in tissue levels of GFAP mRNA or of 28S rRNA in schizophrenic and control patients. These alterations in tissue levels of synaptophysin and SNAP-25 are consistent with the idea that the clinically observed 'hypofrontality' of schizophrenia arises from abnormalities of synaptic number or structural integrity in prefrontal cortex.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autopsy
  • Female
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism*
  • Humans
  • Male
  • Membrane Proteins*
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / pathology
  • RNA, Messenger
  • Reference Values
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism*
  • Schizophrenia / pathology
  • Synapses / metabolism
  • Synapses / pathology
  • Synaptophysin / genetics
  • Synaptophysin / metabolism*
  • Synaptosomal-Associated Protein 25
  • Transcription, Genetic*


  • Glial Fibrillary Acidic Protein
  • Membrane Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • SNAP25 protein, human
  • Synaptophysin
  • Synaptosomal-Associated Protein 25