Schizotypal dimensions: An intermediate phenotype associated with the COMT high activity allele

Background: Although catechol‐O‐methyltransferase (COMT) has long been suggested to be implicated in the pathogenesis of schizophrenia, association studies have generated discrepant results concerning the involvement of the COMT gene in schizophrenia. As several studies have suggested that schizotypal traits might be genetically related to schizophrenia, increased statistical power to detect gene effects could be obtained by using dimensional personality traits in unaffected relatives. Methods: We tested the hypothesis that the functional Val158Met COMT polymorphism might contribute to the variance of self‐reported schizotypal scores in a sample of 106 unaffected subjects, composed of controls (N = 57), first‐degree relatives of schizophrenic (N = 27) and of bipolar (N = 22) probands. We also looked for specific associations between COMT polymorphisms and the three dimensions of schizotypy (positive, negative, disorganized) assessed by the Schizotypal Personality Questionnaire (SPQ). Results: We found that self‐reported SPQ scores are related to COMT genotype ( P  = 0.01), with individuals homozygous for the high activity allele having the highest scores. This association is primarily due to specific associations with the positive ( P  = 0.001) and negative ( P  = 0.04) dimensions. Conclusions: Our data support the hypothesis that the functional COMT polymorphism could be involved in different psychotic dimensions. This confirms that studying specific schizotypal dimensions can help to identify the genes involved in the pathogenesis of psychosis. Copyright © 2006 Wiley‐Liss, Inc., A Wiley Company