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Presynaptic dopaminergic dysfunction in schizophrenia: a positron emission tomographic [18F]fluorodopa study
Stephen McGowan1, Andrew D Lawrence, Tim Sales
1Cyclotron Unit, Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, Imperial College, London, England.
Archives of General Psychiatry
|February 6, 2004
Summary
Schizophrenia patients show increased dopamine activity in the brain's ventral striatum, supporting the dopamine overactivity hypothesis. This study used [18F]fluorodopa PET scans to examine presynaptic dopaminergic function in medicated individuals.
Area of Science:
- Neuroscience
- Psychiatry
- Radiology
Background:
- The dopamine overactivity hypothesis is a leading theory for schizophrenia pathophysiology.
- Radiotracer brain imaging directly investigates this hypothesis.
Purpose of the Study:
- To evaluate presynaptic dopaminergic function in schizophrenia patients using [18F]fluorodopa PET.
- To test predictions of elevated striatal and reduced prefrontal cortical [18F]fluorodopa uptake.
Main Methods:
- A case-control study involving 16 medicated male schizophrenia outpatients and 12 healthy male volunteers.
- High-sensitivity 3D positron emission tomography (PET) with [18F]fluorodopa.
- Analysis of [18F]fluorodopa uptake constant (Ki) using statistical parametric mapping and region-of-interest analyses.
Main Results:
- Increased [18F]fluorodopa uptake was observed in the ventral striatum of schizophrenia patients (P<.05 corrected).
- No significant reduction in prefrontal cortical [18F]fluorodopa uptake was detected.
- Dorsal anterior cingulate [18F]fluorodopa uptake correlated with Stroop test performance in both groups.
Conclusions:
- Medicated patients with schizophrenia exhibit presynaptic striatal dopamine dysfunction.
- These findings provide in vivo support for the dopamine overactivity hypothesis in schizophrenia.
- Dopamine dysfunction is evident even in medicated patients.