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Striatal dopamine release in schizophrenia comorbid with substance dependence
J L Thompson1, N Urban, M Slifstein
1Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Molecular Psychiatry
|August 8, 2012
Summary
Patients with comorbid schizophrenia and substance dependence exhibit blunted dopamine release in the striatum. This dopamine release reduction is linked to positive symptom changes, suggesting altered postsynaptic dopamine D2 receptor function.
Area of Science:
- Neuroscience
- Psychiatry
- Radiology
Background:
- Dopamine (DA) plays a crucial role in schizophrenia and addiction pathophysiology.
- Striatal DA release is elevated in schizophrenia (precommissural caudate) and blunted in addiction (ventral striatum).
- Understanding DA release in comorbid schizophrenia and substance dependence is essential.
Purpose of the Study:
- To measure striatal dopamine release in patients with comorbid schizophrenia and substance dependence.
- To compare dopamine release between patients and healthy controls using neuroimaging.
- To investigate the relationship between dopamine release and psychiatric symptoms.
Main Methods:
- Utilized [(11)C]raclopride positron emission tomography and an amphetamine challenge.
- Measured baseline dopamine D2-receptor availability (BPND) and amphetamine-induced DA release (ΔBPND).
- Analyzed striatal subregions in 11 unmedicated patients and 15 healthy controls.
Main Results:
- No significant group differences in baseline D2-receptor availability (BPND).
- Patients showed significantly blunted amphetamine-induced DA release (ΔBPND) across striatal subregions, except the ventral striatum.
- Dopamine release (ΔBPND) in the precommissural caudate and ventral striatum correlated with positive symptom changes post-amphetamine.
Conclusions:
- Comorbid schizophrenia and substance dependence are associated with blunted striatal dopamine release, unlike schizophrenia alone.
- Despite blunted release, dopamine dynamics correlate with amphetamine-induced positive symptoms.
- Findings suggest abnormal postsynaptic D2 receptor function in patients with low presynaptic DA release.
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