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.