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Clinical involvement of catechol-O-methyltransferase polymorphisms in schizophrenia spectrum disorders: influence on the severity of psychotic symptoms and on the response to neuroleptic treatment

The Pharmacogenomics Journal volume 7, pages 418–426 (2007)Cite this article

Abstract

Genetic variation in the catechol-O-methyltransferase (COMT) gene may influence the susceptibility to schizophrenia and the response to neuroleptic treatment. The authors tested for an association between a COMT haplotype and schizophrenia-spectrum disorders and for an eventual influence of a specific COMT genotype in the clinical outcome and in the response to treatment. The genotypes for single nucleotide polymorphisms rs737865, rs4633, rs6267, rs4680 (Val158Met) and rs165599 were determined in 207 patients with schizophrenia-spectrum disorders and 204 paired controls. Statistical tests for linkage disequilibrium and for case–control differences in haplotype frequencies were performed using log-linear modelling embedded within the expectation-maximization algorithm. P-values based on permutations were calculated using the software UNPHASED, and odds ratios were estimated using the SHEsis platform. The response to neuroleptic treatment was assessed by the Global Assessment of Functioning scale and the severity of psychotic symptoms by the positive and negative syndrome scale (PANSS) scale. The overall disease status was significantly associated with the T-G (Val) diplotype for rs4633–rs4680 (P=0.0049). A significant association was observed between schizophrenia, but not other related disorders, and genotypes GG (Val/Val) for rs4680 and TT for rs4633. Val/Val patients with schizophrenia showed a higher severity of the psychotic symptoms and a worse response to the neuroleptic treatment. COMT genetic variation seems to be involved in the psychotic symptomatology of the schizophrenia-spectrum disorders and specifically in the narrow schizophrenia phenotype. Our results show an influence of the Val158Met polymorphism on the severity of psychotic symptoms and on the response to treatment.

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Abbreviations

COMT:

catechol-O-methyltransferase

EM:

expectation-maximization

HWE:

Hardy–Weinberg equilibrium

MB-COMT:

membrane-bound COMT

SNP:

single nucleotide polymorphism

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Acknowledgements

This work has been supported by a grant from the Education Department of the Government of Navarra (Grant number 16/2002) and by a PIUNA Grant from the University of Navarra (Grant number 13148311). We are grateful to Lucia Marrodan for technical assistance, to Dr María Jesús Arranz for her advice in the measurement of the response to treatment and to Dr José Luis Santos for statistical advice.

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Authors and Affiliations

  1. Department of Psychiatry, University Clinic of Navarra, Pamplona, Spain

    P Molero & F Ortuño

  2. Department of Pediatrics, University Clinic of Navarra, Pamplona, Navarra, Spain

    M Zalacain & A Patiño-García

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  1. P Molero
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  2. F Ortuño
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Correspondence to P Molero.

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Molero, P., Ortuño, F., Zalacain, M. et al. Clinical involvement of catechol-O-methyltransferase polymorphisms in schizophrenia spectrum disorders: influence on the severity of psychotic symptoms and on the response to neuroleptic treatment. Pharmacogenomics J 7, 418–426 (2007). https://doi.org/10.1038/sj.tpj.6500441

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