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

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

doi:10.1016/j.pscychresns.2010.05.002

« Previous Next »Psychiatry Research: Neuroimaging
Volume 183, Issue 2 , Pages 151-156, 30 August 2010

Regional increase in P-glycoprotein function in the blood-brain barrier of patients with chronic schizophrenia:

A PET study with [¹¹C]verapamil as a probe for P-glycoprotein function

Onno L. de Klerk
- Department of Psychiatry, University Medical Center Groningen (UMCG), P.O. Box 30.001, 9700 RB Groningen, The Netherlands
- Psychiatric Hospital GGZ Drenthe, P.O. Box 30007, 9400 RA Assen, The Netherlands
- Corresponding author. Department of Psychiatry, University Medical Center Groningen (UMCG), P.O. Box 30.001, 9700 RB Groningen, The Netherlands. Tel.: +31 50 3612056; fax +31 50 3619132.
Antoon T.M. Willemsen
- Department of Nuclear Medicine and Molecular Imaging, UMCG, Groningen, The Netherlands
Fokko J. Bosker
- Department of Psychiatry, University Medical Center Groningen (UMCG), P.O. Box 30.001, 9700 RB Groningen, The Netherlands
Anna L. Bartels
- Department of Neurology, UMCG, Groningen, The Netherlands
N. Harry Hendrikse
- Department of Nuclear Medicine and PET Research, VU Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands
Johan A. den Boer
- Department of Psychiatry, University Medical Center Groningen (UMCG), P.O. Box 30.001, 9700 RB Groningen, The Netherlands
Rudy A. Dierckx
- Department of Nuclear Medicine and Molecular Imaging, UMCG, Groningen, The Netherlands

Received 26 July 2009; received in revised form 7 February 2010; accepted 6 May 2010.

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 [¹¹C]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 [¹¹C]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 [¹¹C]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.

Keywords: P-glycoprotein, Positron emission tomography, [¹¹C]verapamil, Schizophrenia, Blood-brain barrier