Analysis of gene expression in Schizophrenia using DNA microarrays

How can microarrays be employed to elucidate the underlying pathophysiology of schizophrenia? We describe experiments performed by our group and others, in which DNA microarrays were employed to probe samples from human postmortem brain tissue to examine gene expression differences in schizophrenia. Genes for which decreases in expression were identified fell into two categories. First, decreases in the expression of genes related to presynaptic, glutamatergic, and gamma aminobutyric acid-ergic function have been identified. Secondly, preliminary studies have identified changes in gene expression that are suggestive of cellular stress or sublethal injury were found. We therefore suggest the following hypothesis. An underlying deficit in trophic, developmental, or regulatory processes in schizophrenia places stress on certain subpopulations of neurons. As a result of this cellular stress; these neurons downregulate neurotransmitter and synaptic function. This impaired neurotransmitter and synaptic function may be directly related to the symptoms of schizophrenia. We suggest that an underlying defect, which has not yet been identified, may impair or stress the function of certain neurons, and is ultimately responsible for the pathophysiology of schizophrenia. Further microarray experiments with larger cohorts of subjects and pooling of results across laboratories may lead to further insights into defects in gene expression in schizophrenia and eventually to pharmacologic treatments based on these defects.