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A novel protein isoform of catechol O-methyltransferase (COMT): brain expression analysis in schizophrenia and bipolar disorder and effect of Val158Met genotype

Molecular Psychiatry volume 11, pages 116–117 (2006)Cite this article

Recent studies, including several in this journal, have revived interest in the catecholamine metabolising enzyme catechol-O-methyltransferase (COMT), and suggest strongly that it is involved in the dopaminergic regulation of the prefrontal cortex (PFC), and its dysfunction in schizophrenia.1, 2, 3 These effects are mediated, at least in part, by the Val158Met polymorphism which influences the activity of the enzyme, and are probably modified by other variables, including the expression of soluble (S-COMT) and membrane-bound (MB-COMT) isoforms. Here, we report an additional and potentially important feature of COMT: the occurrence of two variants of MB-COMT protein in human PFC, and the possibility that they are differentially regulated in schizophrenia and bipolar disorder, and in association with the Val158Met genotype.

Total protein was extracted from the PFC of 60 individuals (56 Caucasians) from the Stanley Medical Research Institute Neuropathological Consortium,4 genotyped for the COMT Val158Met polymorphism.5 COMT protein was quantified using enzyme-linked immunosorbent assay (ELISA), and the relative expression of COMT isoforms was investigated using SDS-PAGE and Western blotting. Proteins were separated on 15% tris-glycine polyacrylamide gels and electrophoresis was continued until clear separation of the 31 kDa and 39 kDa markers of a kaleidoscope prestained marker (Biorad, UK) was observed, to ensure high resolution. Both ELISA and Western blotting used a previously described anti-COMT antibody6 (Chemicon, UK) that recognises both S- and MB-COMT. Data were analysed with analysis of variance (ANOVA) and LSD post hoc tests. The effects of potential confounders were investigated using Pearson's coefficient and were included as covariates where appropriate.

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Authors and Affiliations

  1. Department of Psychiatry, University of Oxford, Oxford, UK

    E M Tunbridge & P J Harrison

  2. US Department of Health and Human Services, Genes, Cognition and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, MD, USA

    E M Tunbridge & D R Weinberger

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  1. E M Tunbridge
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  2. D R Weinberger
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  3. P J Harrison
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Correspondence to E M Tunbridge.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp).

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Tunbridge, E., Weinberger, D. & Harrison, P. A novel protein isoform of catechol O-methyltransferase (COMT): brain expression analysis in schizophrenia and bipolar disorder and effect of Val158Met genotype. Mol Psychiatry 11, 116–117 (2006). https://doi.org/10.1038/sj.mp.4001767

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