COMT Val 108/158 Met polymorphism and treatment response to aripiprazole in patients with acute schizophrenia

Abstract

Introduction

The COMT Val 108/158 Met polymorphism (rs4680) may affect treatment response to antipsychotics, as well as metabolism and dynamics of neurotransmitters during the treatment of schizophrenia. We investigated the effects of the COMT Val 108/158 Met polymorphism on treatment response to aripiprazole and plasma monoamine metabolite levels in patients with acute schizophrenia.

Materials and methods

Forty patients with schizophrenia were treated with aripiprazole for 6 weeks. We measured Positive and Negative Syndrome Scale (PANSS) and plasma levels of homovanillic acid (HVA) and plasma MHPG (3-methoxy-4-hydroxyphenethyleneglycol) at baseline and endpoint. The COMT Val 108/158 Met polymorphism was genotyped with the polymerase chain reaction and restriction fragment length polymorphism.

Results

There were significant genotype–time interactions on PANSS total and general psychopathology scores, with Met/Met genotype showing greater improvement. The response rate to aripiprazole did not differ between COMT Val 108/158 Met genotype groups. We found a significant time effect on plasma MHPG levels, but no time effect on plasma HVA levels or time–genotype interactions in the plasma levels of HVA and MHPG. Although the responder rate did not differ among the 3 genotype groups.

Conclusion

Our results suggest that individuals with the Met/Met genotype had greater improvement in PANSS score after the treatment with aripiprazole. On the other hand, the Val 108/158 Met polymorphism may not induce changes in plasma levels of monoamine metabolites during aripiprazole treatment. Because of the small sample size, further studies are needed to confirm and to extend our results.

Keywords:

• schizophrenia
• COMT
• Val 108/158 Met polymorphism (rs4680)
• aripiprazole
• pharmacogenetics

Supplementary material

Table S1 Comparisons between responders and nonresponders

Acknowledgments

The authors thank Kazuko Kanno for help with running polymerase chain reaction experiments.

Disclosure

zThe authors report no conflicts of interest in this work.