Association study of COMT gene Val158Met polymorphism with auditory P300 and performance on neurocognitive tests in patients with schizophrenia and their relatives.

A number of studies have reported an association between catechol-O-methyltransferase (COMT) gene Val158Met polymorphism and neuropsychological traits in patients with schizophrenia, their relatives and healthy controls, with the Met allele carriers performing better on neurocognitive tasks than those with the Val allele. But the association was not confirmed in all studies. The present paper was aimed at further investigation of the COMT gene relationship with some neurocognitive traits, assessing mainly working and verbal memory, and to P300 event-related potentials (auditory oddball). A total sample of 319 individuals, including schizophrenic patients, their relatives and controls, was studied. No significant differences in performance of neurocognitive tasks were found by Val158Met genotypes. An association was observed between the Met/Met genotype and higher amplitude in centro-parietal area in relatives. Factors that could explain the non-replication of previous studies on the COMT gene polymorphism and neurocognitive traits are discussed. We suggest here that (1) Val158Met polymorphism rather exerts a modifying influence on brain activation in general than impacts directly on performance of the particular neurocognitive test, and (2) P300 amplitude seems to be a correlate of this activation reflecting, along with information processing, the subject's affective and personality features.