Catechol-O-Methyltransferase Val-108/158-Met Gene Variants Associated With Performance on the Wisconsin Card Sorting Test

Because of its location in a region previously linked to schizophrenia (22q),¹ and its critical involvement in the homeostasis of dopamine metabolism in brain regions relevant for schizophrenia, such as the dorsolateral prefrontal cortex (DLPFC),^2- 3 it was hypothesized that allelic variants of the catechol-O-methyltransferase (COMT) gene may modulate the risk for this disorder. Recently, in accordance with this hypothesis, an allele coding for an isoform with high enzymatic activity of the COMT (Val allele of the Val-108/158-Met polymorphism) was associated or linked to schizophrenia.⁴ Moreover, it was shown in that study, part of the variance for the Wisconsin Card Sorting Test (WCST; a neuropsychological test that maps mainly into the DLPFC), performance was explained by the Val-108/158-Met polymorphism, both in schizophrenic patients and in healthy controls, where subjects carrying 1 or 2 copies of the Val allele performed significantly worse on the WCST compared with those who were homozygous for the Met allele. A similar observation was made for the degree of bold activation in the DLPFC, measured by means of functional magnetic resonance imaging, in 2 groups of nonaffected siblings of schizophrenic patients while performing working memory tasks.