Comparative proteome analysis of the hippocampus implicates chromosome 6q in schizophrenia

Comparative brain proteome analysis is a new strategy to discover proteins and therefore genes whose altered expression may underlie schizophrenia. Th is strategy does not require an a priori theory of the pathogenesis or the mode of inheritance of schizophrenia. Using proteome analysis we previously compared the hippocampal proteome, that is, those proteins expressed by th e hippocampal genome, of seven schizophrenic individuals with the hippocamp al proteome of seven control individuals, matched for age and post mortem d elay.(1) We found 18 proteins that were significantly altered in concentrat ion in the schizophrenic hippocampus (P < 0.05), when compared to control t issue. One of these proteins was characterised, by N-terminal sequencing, a s diazepam binding inhibitor whose gene maps to 6q12-q21. Here we character ise a further three of the 18 proteins as: manganese superoxide dismutase, 6q25.3, T-complex protein 1, 6q25,3-q26 and collapsin response mediator pro tein 2, 8p21. That three of these four characterised proteins should map to the long arm of the same chromosome is significant (P < 0.002) and suggest s the importance of chromosome 6q in schizophrenia. These results indicate that antioxidant defence is altered in the schizophrenic hippocampus and su ggest that segregation distortion, of schizophrenia susceptibility genes, m ay be a possible causative factor in the high incidence of schizophrenia.