Changed gene expression in Brodmann's area 9 in schizophrenia: support for a molecular pathology affecting membrane transporters and regulators involved in multiple neurotransmitter systems.

OBJECTIVES: To identify changes in RNA levels in Brodmann's area 9 (BA 9) from people with schizophrenia compared to controls and to understand the contribution of those changes to the molecular pathology of the disorder.

METHODS: BA 9 RNA levels, measured in 81 people with schizophrenia and 70 healthy controls using the Affymetrix Human Exon 1.0 ST Array, were compared using JMP Genomics 9.0. Differences in levels of RNA between diagnosis were accepted at fold changes of 1.0 ± ≥ 0.2 and p < 0.01. The potential effects of these changes in RNA were determined using the Panther Gene Ontology Classification System and Qiagen Ingenuity Pathways.

RESULTS: Levels of 17,304 RNAs were measured in BA 9, with 47 RNA levels being altered (29 higher) in schizophrenia. These changes in RNA levels should affect water homeostasis, regulation of extracellular space volume, potassium buffering, CSF circulation, interstitial fluid resorption, waste clearance, neuroinflammation, osmosensation, cell migration, calcium signalling and transport, gap junctions and membrane transport.

CONCLUSIONS: Changes in gene expression we report in BA 9 from people with schizophrenia are involved in important biochemical pathways that could contain new drug targets and could be involved in the molecular pathology of the disorder.