MDR1 gene polymorphisms and response to acute risperidone treatment.
Matej Kastelic1, Jure Koprivsek, Blanka Kores Plesnicar
1Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. matej.kastelic@mf.uni-lj.si
Progress in Neuro-Psychopharmacology & Biological Psychiatry
|January 12, 2010
Summary
Polymorphic multidrug resistant protein 1 (MDR1) gene variants did not significantly impact risperidone treatment response or parkinsonism risk in schizophrenia patients. Minor associations were found with akathisia and dystonia, but not a clear gene-dose effect.
Area of Science:
- Pharmacogenetics
- Neuroscience
- Psychiatry
Background:
- Polymorphic multidrug resistant protein 1 (MDR1) influences drug transport across the blood-brain barrier.
- MDR1 genetic variations may affect antipsychotic efficacy and side effects, independent of plasma levels.
- Understanding MDR1's role is crucial for personalized schizophrenia treatment.
Purpose of the Study:
- To investigate the impact of MDR1 C3435T and G2677T/A polymorphisms on risperidone treatment outcomes in Slovenian schizophrenia patients.
- To assess the association between these MDR1 genotypes and psychopathological symptom improvement.
- To evaluate the relationship between MDR1 polymorphisms and the occurrence of extrapyramidal side effects (EPS).
Main Methods:
- Genotyping of MDR1 C3435T and G2677T/A polymorphisms in 59 schizophrenia patients.
- Measurement of steady-state plasma concentrations of risperidone active moiety.
- Assessment of psychopathological symptoms and EPS using standardized scales (AIMS, BARS).
Main Results:
- MDR1 G2677T/A and C3435T genotypes showed no significant association with overall treatment efficacy or parkinsonism risk.
- Marginal associations were observed between both genotypes and akathisia (p=0.039-0.042) and dystonia (p=0.013-0.034).
- Higher scores for AIMS and BARS were noted in heterozygous carriers, without a clear gene-dose effect.
Conclusions:
- The study suggests MDR1 G2677T/A and C3435T polymorphisms do not have a major influence on short-term risperidone treatment response in schizophrenia.
- While marginal associations with specific EPS exist, they do not appear to be dose-dependent.
- Further research may be needed to clarify the complex role of MDR1 in antipsychotic pharmacogenetics.
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