Regional increase in P-glycoprotein function in the blood-brain barrier of patients with chronic schizophrenia: A PET study with [C-11]verapamil as a probe for P-glycoprotein function

Onno L. de Klerk*, Antoon T. M. Willemsen, Fokko J. Bosker, Anna L. Bartels, N. Harry Hendrikse, Johan A. den Boer, Rudy A. Dierckx

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    46 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)151-156
    Number of pages6
    JournalPsychiatry research-Neuroimaging
    Volume183
    Issue number2
    DOIs
    Publication statusPublished - 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

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