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Phil Ok Koh, PhD; Clare Bergson, PhD; Ashiwel S. Undie, PhD; Patricia S. Goldman-Rakic, PhD; Michael S. Lidow, PhD

Arch Gen Psychiatry. 2003;60:311-319.

Background  The dopamine hypothesis remains a prominent influence on research into the pathogenesis of schizophrenia, yet the presence of consistent schizophrenia-linked abnormalities in the presynaptic components of the dopamine system or in dopamine receptors still remains a matter of debate. The present study focuses on a recently recognized group of dopamine receptor–interacting proteins as possible novel sites of dysfunction in schizophrenia. Specifically, we examined whether the D1 dopamine receptor–interacting protein calcyon and the D2 dopamine receptor–interacting proteins filamin-A and spinophilin are affected in the dorsolateral prefrontal cortex of patients with schizophrenia.

Methods  Slot blots of dorsolateral prefrontal cortical tissue were used to compare the levels of the 3 proteins of interest in control, schizophrenic, bipolar, and major depression groups (n = 15 per group). The nonschizophrenic psychiatric groups were included to determine the specificity of the detected abnormalities.

Results  The dorsolateral prefrontal cortex in schizophrenic patients displayed nearly twice the normal levels of calcyon, whereas filamin-A and spinophilin levels were unaltered. Patients with bipolar disorder or major depression showed no changes in all 3 proteins examined.

Conclusion  Our findings provide the first evidence that abnormalities in the dopamine system of patients with schizophrenia may lie in altered levels of dopamine receptor–interacting proteins.

From the Departments of Oral and Craniofacial Biological Sciences (Drs Koh and Lidow) and Pharmaceutical Sciences (Dr Undie), University of Maryland, Baltimore; the Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta (Dr Bergson); and the Department of Neurobiology, Yale University, New Haven, Conn (Dr Goldman-Rakic).

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