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McGowan S, Lawrence AD, Sales T, Quested D, Grasby P. Presynaptic Dopaminergic Dysfunction in Schizophrenia: A Positron Emission Tomographic [18F]Fluorodopa Study. Arch Gen Psychiatry. 2004;61(2):134–142. doi:https://doi.org/10.1001/archpsyc.61.2.134
The dopamine overactivity hypothesis of schizophrenia remains one of
the most influential theories of the pathophysiology of the illness. Radiotracer
brain imaging studies are now directly testing aspects of the overactivity
To assess presynaptic dopaminergic function in a large cohort of patients
with schizophrenia by means of [18F]fluorodopa uptake and a high-sensitivity
3-dimensional positron emission tomograph. We predicted elevations in striatal
[18F]fluorodopa uptake and reductions in prefrontal cortical [18F]fluorodopa uptake in patients with schizophrenia.
Research institute investigation recruiting hospital outpatients.
Sixteen male medicated hospital outpatients with a DSM-IV diagnosis of schizophrenia (mean age, 38 years) and 12 age-matched
male volunteers free of psychiatric and neurologic illness.
[18F]fluorodopa positron emission tomographic scanning.
Main Outcome Measure
[18F]fluorodopa uptake constant Ki measured with statistical parametric mapping and region-of-interest
Statistical parametric mapping (P<.05 corrected)
and region-of-interest analyses (P<.01) showed
increased [18F]fluorodopa uptake, confined primarily to the ventral
striatum in patients with schizophrenia. No reductions in prefrontal cortical
[18F]fluorodopa uptake Ki were
seen in the statistical parametric mapping and region-of-interest analyses,
although dorsal anterior cingulate [18F]fluorodopa Ki correlated with performance on the Stroop Color-Word
Test in both groups.
As in studies in unmedicated patients, presynaptic striatal dopamine
dysfunction is present in medicated schizophrenic patients, adding further
in vivo support for dopamine overactivity in the illness.
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