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Focal Abnormalities in Orbitofrontal Cortex in Schizophrenia

James H. Meador-Woodruff, MD; Vahram Haroutunian, PhD; Peter Powchik, MD; Michael Davidson, MD; Kenneth L. Davis, MD; Stanley J. Watson, PhD, MD

Arch Gen Psychiatry. 1997;54(12):1089-1095.

Abstract
Background
The identification of novel subtypes of the dopamine receptors has renewed interest in the involvement of dopaminergic mechanisms in schizophrenia. We determined the expression of transcripts encoding the dopamine receptors in the brains of schizophrenic patients.

Methods
The levels of the messenger RNA molecules encoding the 5 dopamine receptors were quantified in postmortem brain samples from 16 schizophrenic patients and 9 control subjects. Samples from multiple regions of the prefrontal cortex, primary visual cortex, and striatum were subjected to in situ hybridization followed by quantitative image analysis.

Results
Expression of dopamine receptor transcripts did not differ between schizophrenic patients and controls in striatum or visual cortex. Dramatic decreases of dopamine receptor transcripts were found in the prefrontal cortex, but these changes were restricted to the D₃ and D₄ receptors, and localized to Brodmann area 11 (orbitofrontal cortex).

Conclusions
Cortical dopaminergic neurotransmission may be disrupted in schizophrenia at the level of receptor expression. There appears to be a focal abnormality of D₃ and D₄ messenger RNA expression in the prefrontal cortex, with down-regulation of both, consistent with prefrontal cortical hypodopaminergia in schizophrenia.

Author Affiliations
From the Mental Health Research Institute, Department of Psychiatry, University of Michigan, Ann Arbor (Drs Meador-Woodruff and Watson); the Department of Psychiatry, Mount Sinai School of Medicine, New York, NY (Drs Haroutunian, Powchik, and Davis); and The Chaim Sheba Medical Center, Tel-Hashomer, Israel (Dr Davidson).

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