Differential patterns of dopamine receptor gene expression in schizophrenia

Dysregulation of dopaminergic neurotransmission has been implicated in the pathogenesis and/or symptomatology of schizophrenia. Recently identified novel subtypes of the dopamine receptors have been suggested to be involved in this illness, particularly the D3 and D4 subtypes. We have initiated a large-scale study designed to examine the expression of the messenger RNAs encoding the five known dopamine receptors in sectioned postmortem brain tissue from schizophrenics and appropriate controls, to address the anatomically-specific expression of these receptor genes in a quantitative fashion. Further, we have studied schizophrenic brain tissue from both neuroleptic-treated and medication-free subjects, in order to determine the effects of antipsychotics on the expression of dopamine receptors in human brain. We are systematically examining the expression of these mRNAs in linked anatomical regions within two brain circuits that have been implicated in this illness: the corticostriatal-pallidothalamocortical loop, and the circuitry involving the medial temporal lobe structures associated with the hippocampus. Our results reveal a complex and differential expression of these mRNAs in schizophrenic brain, but in region- and message-specific patterns) while some of the changes in schizophrenic brain appear due to the effects of chronic antipsychotic treatment, others appear to be associated specifically with the illness itself. These results suggest that dopaminergic neurotransmission is disrupted in schizophrenia at the level of dopamine receptor expression. Further, we have found that this dysfunction of the dopamine system does not occur globally, but is rather region- and circuit-specific.