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Original Article
February 2004

Presynaptic Dopaminergic Dysfunction in Schizophrenia: A Positron Emission Tomographic [18F]Fluorodopa Study

Author Affiliations

From the Cyclotron Unit, Medical Research Council Clinical SciencesCentre, Hammersmith Hospital, Imperial College, London, England (Drs McGowanand Grasby); Medical Research Council Cognition and Brain Sciences Unit, Cambridge,England (Dr Lawrence); and University Department of Psychiatry, WarnefordHospital, Headington, Oxford, England (Drs Sales and Quested).

Arch Gen Psychiatry. 2004;61(2):134-142. doi:10.1001/archpsyc.61.2.134

Context  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 hypothesis.

Objective  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.

Design  Case-control study.

Setting  Research institute investigation recruiting hospital outpatients.

Patients  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.

Intervention  [18F]fluorodopa positron emission tomographic scanning.

Main Outcome Measure  [18F]fluorodopa uptake constant Ki measured with statistical parametric mapping and region-of-interest analyses.

Results  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.

Conclusions  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.