Gene expression changes in schizophrenia: How do they arise and what do they mean?

The advent of different methods for quantifying messenger RNAs has made it possible to assess the tissue levels of the transcription products of virtually every gene expressed in the human brain, and to determine whether the expression of each gene is altered in psychiatric disorders such as schizophrenia. However, these advances have raised a number of interpretive questions, including what causes disease-related mRNA expression changes and what such changes mean for the function of the affected brain circuits. In this paper, we consider possible answers to these questions for two genes, Regulator of G Protein Signaling 4 (RGS4) and the 67 kilodalton isoform of glutamic acid decarboxylase (GAD₆₇), both of which have been found to be under-expressed in the prefrontal cortex of subjects with schizophrenia.