Catechol-O-methyl Transferase and Expression of Schizophrenia in 73 Adults with 22q11 Deletion Syndrome

  • Anne S. Bassett
    Address reprint requests to Anne S. Bassett, M.D., F.R.C.P.C., Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, Ontario M6J 1H4 Canada
    Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    Division of Cardiology, Department of Medicine, University Health Network, Toronto, Ontario, Canada
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  • Oana Caluseriu
    Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
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  • Rosanna Weksberg
    Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
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  • Donald A. Young
    Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    Division of Clinical and Metabolic Genetics, Hospital for Sick Children, and Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
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  • Eva W.C. Chow
    Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
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      Catechol-O-methyl transferase (COMT) is a candidate gene for schizophrenia with a role in dopamine metabolism, particularly in frontal cortex. COMT is within the region commonly deleted in 22q11 deletion syndrome (22q11DS), a syndrome with high prevalence of schizophrenia. We examined the role of COMT in schizophrenia-related expression in 22q11DS.


      We genotyped the COMT functional Val158/108Met allele in 73 Caucasian adults with 22q11DS (36 men, 37 women; aged 33.8, SD 10.1 years; 37 Met, 36 Val hemizygosity) blind to clinical data and assessed effects on symptoms and frontal functioning.


      The lower activity Met allele was not significantly more prevalent than the Val allele in 33 subjects with schizophrenia. Excitement symptoms were more severe, however, and three frontal cognitive tests (theory of mind, Trails B, and olfactory identification), communication, and social functioning measures showed significantly worse performance with Met allele hemizygosity, even after accounting for effects of schizophrenia.


      The results suggest that hemizygosity of the COMT functional allele exerts an effect on some measures of frontal functioning in 22q11DS. Elevated levels of tonic dopamine activation associated with the COMT Met allele may underlie these aspects of expression. We must look elsewhere for causes of the high prevalence of schizophrenia in 22q11DS, however.

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