Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium

Mol Psychiatry. 2000 Mar;5(2):142-9. doi: 10.1038/sj.mp.4000696.


Severe psychiatric disorders such as schizophrenia, bipolar disorder and major depressive disorder are brain diseases of unknown origin. No biological marker has been documented at the pathological, cellular, or molecular level, suggesting that a number of complex but subtle changes underlie these illnesses. We have used proteomic technology to survey postmortem tissue to identify changes linked to the various diseases. Proteomics uses two-dimensional gel electrophoresis and mass spectrometric sequencing of proteins to allow the comparison of subsets of expressed proteins among a large number of samples. This form of analysis was combined with a multivariate statistical model to study changes in protein levels in 89 frontal cortices obtained postmortem from individuals with schizophrenia, bipolar disorder, major depressive disorder, and non-psychiatric controls. We identified eight protein species that display disease-specific alterations in level in the frontal cortex. Six show decreases compared with the non-psychiatric controls for one or more diseases. Four of these are forms of glial fibrillary acidic protein (GFAP), one is dihydropyrimidinase-related protein 2, and the sixth is ubiquinone cytochrome c reductase core protein 1. Two spots, carbonic anhydrase 1 and fructose biphosphate aldolase C, show increase in one or more diseases compared to controls. Proteomic analysis may identify novel pathogenic mechanisms of human neuropsychiatric diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Autopsy
  • Bipolar Disorder / metabolism*
  • Carbonic Anhydrases / chemistry
  • Carbonic Anhydrases / metabolism
  • Depressive Disorder / metabolism*
  • Electron Transport Complex III / chemistry
  • Electron Transport Complex III / metabolism
  • Electrophoresis, Gel, Two-Dimensional
  • Frontal Lobe / chemistry
  • Frontal Lobe / metabolism*
  • Fructose-Bisphosphate Aldolase / chemistry
  • Fructose-Bisphosphate Aldolase / metabolism
  • Glial Fibrillary Acidic Protein / chemistry
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Image Processing, Computer-Assisted
  • Molecular Sequence Data
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Peptide Fragments / chemistry
  • Reference Values
  • Schizophrenia / metabolism*


  • CRMP1 protein, human
  • Glial Fibrillary Acidic Protein
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Fructose-Bisphosphate Aldolase
  • Carbonic Anhydrases
  • Electron Transport Complex III