Abstract
P-glycoprotein (P-gp), a major efflux pump in the blood-brain barrier (BBB) has a profound effect on entry of drugs, peptides and other substances into the central nervous system (CNS). The brain's permeability can be negatively influenced by modulation of the transport function of P-gp. Inflammatory mediators play a role in schizophrenia, and may be able to influence the integrity of the BBB, via P-gp modulation. We hypothesized that P-gp function in the BBB is changed in patients with schizophrenia. Positron-emission tomography was used to measure brain uptake of [C-11]verapamil, which is normally extruded from the brain by P-gp. We found that patients with chronic schizophrenia under treatment with antipsychotic drugs compared with healthy controls showed a significant decrease in [C-11]verapamil uptake in the temporal cortex, the basal ganglia, and the amygdala, and amygdalae, and a trend towards a significant decrease was seen throughout the brain. The decrease of [C-11]verapamil uptake correlates with an increased activity of the P-gp pump. Increased P-gp activity may be a factor in drug resistance in schizophrenia, induced by the use of antipsychotic agents. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
Original language | English |
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Pages (from-to) | 151-156 |
Number of pages | 6 |
Journal | Psychiatry research-Neuroimaging |
Volume | 183 |
Issue number | 2 |
DOIs | |
Publication status | Published - 30-Aug-2010 |
Keywords
- P-glycoprotein
- Positron emission tomography
- [C-11]verapamil
- Schizophrenia
- Blood-brain barrier
- MDR1 GENE POLYMORPHISMS
- NECROSIS-FACTOR-ALPHA
- RISPERIDONE TREATMENT
- THERAPEUTIC RESPONSE
- ANTIPSYCHOTIC-DRUGS
- PARKINSONS-DISEASE
- TRANSPORT ACTIVITY
- ABCB1 GENE
- IN-VITRO
- EXPRESSION