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

Department of Psychiatry, University of Oxford, Oxford, England, United Kingdom
Archives of General Psychiatry (Impact Factor: 14.48). 03/2004; 61(2):134-42. DOI: 10.1001/archpsyc.61.2.134
Source: PubMed


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.
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.
Case-control study.
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 OUTDOME MEASURE: [18F]fluorodopa uptake constant Ki measured with statistical parametric mapping and region-of-interest analyses.
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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    • "For our striatal ROIs, the volume was subdivided as follows: all planes containing striatal structures below the anterior commissure-posterior commissure plane were operationally defined as the ventral striatum (VS) ROI, and all planes above the anterior commissure-posterior commissure plane containing striatal structures formed the dorsal striatum (DS) ROI. The standard object map was applied to the transformed Ki maps and values of FDOPA Ki (units: ml • g−1 • min−1) were obtained for the two striatal ROIs for each individual (McGowan et al., 2004). When performing our ROI analysis a manual correction for head movement was applied as previously described (Whone et al., 2003). "
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