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

• Published in: Psychiatry research. Neuroimaging 2010, Vol.183 (2), p.151-156
• Main Authors: de Klerk, Onno L, Willemsen, Antoon T.M, Bosker, Fokko J, Bartels, Anna L, Hendrikse, N. Harry, den Boer, Johan A, Dierckx, Rudy A
• Format: Article
• Language: English
• Subjects: [ 11C]verapamil; Blood-brain barrier; P-glycoprotein; Positron emission tomography; Psychiatry; Radiology; Schizophrenia
• ISSN: 0925-4927; 1872-7506
• DOI: 10.1016/j.pscychresns.2010.05.002

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 [11 C]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 [11 C]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 [11 C]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.