Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder

Severe psychiatric disorders such as schizophrenia, bipolar disorder and ma jor depressive disorder are brain diseases of unknown origin. No biological marker has been documented at the pathological, cellular, or molecular lev el, suggesting that a number of complex but subtle changes underlie these i llnesses. We have used proteomic technology to survey postmortem tissue to identify changes linked to the various diseases. Proteomics uses two-dimens ional 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 statisti cal model to study changes in protein levels in 89 frontal cortices obtaine d postmortem from individuals with schizophrenia, bipolar disorder, major d epressive disorder, and non-psychiatric controls. We identified eight prote in species that display disease-specific alterations in level in the fronta l cortex. Six show decreases compared with the non-psychiatric controls for one or more diseases. Four of these are forms of glial fibrillary acidic p rotein (GFAP), one is dihydropyrimidinase-related protein 2, and the sixth is ubiquinone cytochrome c reductase core protein 1, Two spots, carbonic an hydrase 1 and fructose biphosphate aldolase C, show increase in one or more diseases compared to controls. Proteomic analysis may identify novel patho genic mechanisms of human neuropsychiatric diseases.