Protein Alterations in the Postmortem Frontal Lobes of Individuals with Severe Psychiatric Disorders




N. Johnston *, L.

Anderson, N. Anderson, a. Shore, R. Yolken and E.F. Torrey

Johns Hopkins University, Stanley Division of Developmental

Neurovirology, Baltimore MD

Two-dimensional gel electrophoresis is an

objective means to compare the levels of individual proteins in

different samples. We analyzed 89 postmortem frontal cortex brain

regions from individuals with schizophrenia, bipolar disorder,

major depression and unaffected normal controls. Proteins were

separated between 10-200kD and pl of 4-7, stained with Coomassie

blue, matched between gels and quantified. We used a multivariate

analysis to identify changes specific to psychiatric disease. Of

the 217 matched spots, 6 spots were decreased and 2 were

increased in level in one or more illnesses. Four of those which

were decreased were variants of glial fibrilary acidic protein

(GFAP). Ubiquinone cytochrome c reductase complex protein 1 was

reduced in depression, and dihydropyrimidinase related protein 2

was reduced in all three illnesses. Carbonic anhydrase 1 was

elevated in depressed individuals and a second as yet

unidentified protein was elevated in all three diseases.

The GFAP proteins formed a family of spots

that likely include modified and unmodified forms of this

protein. It is noted that two forms were significantly decreased

in all disorders while the other two were only altered in

non-psychotic depression. The pattern of change was distinct

between the three diseases and could not be attributed to any

known confounding variables. Two dimensional gel electrophoresis

offers a sensitive and viable means to measure changes in levels

and modifications that would not be detected by one-dimensional

electrophoresis or analysis of the corresponding nucleic acids.