Altered dopaminergic neurotransmission in the dorsolateral prefrontal cortex, particularly at D1-type receptors, has been implicated in the working memory deficits observed in schizophrenia. This area may also be involved in cognitive and emotional processes in mood disorders, as well as in their responses to antidepressant treatment and transcranial magnetic stimulation. Studies of other regions of prefrontal cortex, namely orbitofrontal cortex, have demonstrated decreases in expression of D3 and D4 receptor transcripts. We investigated expression of dopamine receptor transcripts in the dorsolateral prefrontal cortex of patients with schizophrenia, major depression, and bipolar disorder. In situ hybridization with probes specifically designed for human D1, D2, D3, D4, and D5 receptor transcripts was performed on tissue obtained from the Stanley Foundation Neuropathology Consortium. We also investigated the striatum and the medial temporal cortex (hippocampus, entorhinal cortex, perirhinal cortex) in the same groups.  These data are currently under analysis.  Initial results suggest altered prefrontal expression of all five dopamine receptors in all three psychiatric conditions, but particularly in bipolar disorder.  Various changes were also found in the medial temporal cortex and striatum.  These findings indicate that alterations in dopamine neurotransmission are present in the brains of patients with psychiatric illness.  These abnormalities may influence the ability of dopamine to modulate glutamatergic neurotransmission in cerebral cortex.

Karen Baracskay