Mol Psychiatry 2000 Mr


Mol Psychiatry 2000 Mr;5(2):142-9

Disease-Specific Alterations in Frontal Cortex Brain

Proteins In Schizophrenia, Bipolar Disorder, and Major Depressive Disorder. The

Stanley Neuropathology Consortium

Johnston-Wilson NL, Sims CD, Hofmann JP, Anderson L,

Shore AD, Torrey EF, Yolken RH


Severe psychiatric disorders such as schizophrenia,

bipolar disorder and major depressive 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.