Abstract
Background: The Val158Met single nucleotide polymorphism of the catechol-O-methyltransferase (COMT) gene on chromosome 22 influences dopamine catabolism and is related to cognitive impairment in schizophrenia. Previous research has found that the Met allele is associated in a dose-response fashion with better performance on most neuropsychological tests. Methods: We assessed 138 outpatients with schizophrenia-spectrum disorders (65% men; 59% Caucasian; mean age=49; mean years of education=13) with a blood draw and a comprehensive neuropsychological, functional, and clinical battery. Participantswith the Val/Val (n=49), Val/Met (n=57), and Met/Met (n=32) genotypes did not differ on demographic variables, diagnosis, type or dosage of antipsychotic medication, or duration of psychosis. Results: Spearman correlations between the dose of the Met allele (0, 1, or 2 Met alleles) and the neuropsychological, functional, and clinical variables demonstrated that a higher number of Met alleles was associated with better estimated premorbid intellectual functioning (r=.20, p=.020), verbal memory (r=.18, p=.036), visual memory (r=.17, p=.047), and working memory (r=.17, p=.045). Met carriers significantly outperformed noncarriers on measures of premorbid intellectual functioning (t=2.25, df=136, p=.026), verbal memory (t=2.13, df=136, p=.035), and visual memory (t=2.09, df=119.34, p=.028). Discussion: The Met allele appears to be associated with better performance in premorbid intellectual functioning, delayed verbal and visual recall, and working memory, explaining 3-4% of the variance in these abilities. Associations between COMTgenotype and functional capacity or psychiatric symptom severity were not statistically significant. Because the Val158Met polymorphism typically explains a small amount of variance in cognitive performance and given the size of the current sample, these results need to be replicated with a larger sample and other variants should be considered to further understand genetic contributions to cognition.
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