Catechol-O-methyltransferase and the clinical features of psychosis

J L McClay, A Fanous, E J C G van den Oord, B T Webb, D Walsh, F A O'Neill, K S Kendler, X Chen

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23 Citations (Scopus)


A functional polymorphism (Val-158-Met) at the Catechol-O-methyltransferase (COMT) locus has been identified as a potential etiological factor in schizophrenia. Yet the association has not been convincingly replicated across independent samples. We hypothesized that phenotypic heterogeneity might be diluting the COMT effect. To clarify the putative association, we performed an exploratory analysis to test for association between COMT and five psychosis symptom scales. These were derived through factor analysis of the Operational Criteria Checklist for Psychiatric Illness. Our sample was the Irish Study of High Density Schizophrenia Families, a large collection consisting of 268 multiplex families. This sample has previously shown a small but significant effect of the COMT Val allele in conferring risk for schizophrenia. We tested for preferential transmission of COMT alleles from parent to affected offspring (n = 749) for each of the five factor-derived scales (negative symptoms, delusions, hallucinations, mania, and depression). Significant overtransmission of the Val allele was found for mania (P <0.05) and depression (P = 0.01) scales. Examination of odds ratios (ORs) revealed a heterogeneous effect of COMT, whereby it had no effect on Negative Symptoms, but largest impact on Depression (OR = 1.4). These results suggest a modest affective vulnerability conferred by this allele in psychosis, but will require replication.
Original languageEnglish
Pages (from-to)935-8
Number of pages4
JournalAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Issue number8
Publication statusPublished - 05 Dec 2006

Bibliographical note

(c) 2006 Wiley-Liss, Inc.


  • Catechol O-Methyltransferase
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Ireland
  • Male
  • Odds Ratio
  • Phenotype
  • Polymorphism, Genetic
  • Psychotic Disorders

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