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Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia

Abstract

Both dopaminergic neurotransmission and prefrontal cortex (PFC) function are known to be abnormal in schizophrenia. To test the hypothesis that these phenomena are related, we measured presynaptic dopaminergic function simultaneously with regional cerebral blood flow during the Wisconsin Card Sorting Test (WCST) and a control task in unmedicated schizophrenic subjects and matched controls. We show that the dopaminergic uptake constant Ki in the striatum was significantly higher for patients than for controls. Patients had significantly less WCST-related activation in PFC. The two parameters were strongly linked in patients, but not controls. The tight within-patient coupling of these values, with decreased PFC activation predicting exaggerated striatal 6-fluorodopa uptake, supports the hypothesis that prefrontal cortex dysfunction may lead to dopaminergic transmission abnormalities.

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Figure 1: Statistical maps of regional cerebral blood flow.
Figure 2: Striatal dopamine uptake (Ki) and relationship with DLPFC blood flow.

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Acknowledgements

We would like to acknowledge the support of the staff of the PET Department, Clinical Center, NIH, in the execution of this study and the help of Timothy Ellmore, in data analysis.

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Correspondence to Andreas Meyer-Lindenberg.

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Meyer-Lindenberg, A., Miletich, R., Kohn, P. et al. Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. Nat Neurosci 5, 267–271 (2002). https://doi.org/10.1038/nn804

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