A study of altered gene expression in frontal cortex from schizophrenic patients using differential screening.

In order to examine the molecular basis of schizophrenia we have employed a sequential differential hybridisation protocol to isolate mRNAs whose abundances are altered in schizophrenic compared to normal frontal cortex. Five cDNAs present at abnormal levels in the schizophrenic brain have been isolated by this method. The sequences were identified on the basis of homologies in the EMBL and Genbank databases. All the sequences encode mitochondrial transcripts; one encodes part of the 12s rRNA, three encode parts of the 16s rRNA region of the mitochondrial genome whilst the fourth encodes part of the amino acid sequence of cytochrome oxidase sub-unit II. It was established that mitochondrial sequences were not over-represented in the library and that this could therefore not account for the isolation of five mitochondrial transcripts by this procedure. Increased levels of cytochrome oxidase mRNA were detected in a further set of extracts from the frontal cortex of eight schizophrenic patients and five controls. The amount of mt-DNA was measured in these samples but there was no difference between schizophrenic and control. These results indicate a possible abnormality of mitochondrial function in the schizophrenic frontal cortex.