Effects of catechol-O-methyltransferase enzyme Val158Met polymorphism on cognitive functions in schizophrenic patients

Abstract

Objective: Catechol-O-Methyltransferase (COMT) enzyme plays an important role in dopamine metabolism. Three different genotypes have been defined, one resulting from a valine (val)-> methionine (met) amino acid change due to a guanine -> adenine nucleotide change at codon 108/158 of the COMT gene, while the other two genotypes are formed by alleles containing val (heat-resistant, high activity) and met (heat-sensitive, low activity). This functional polymorphism in the COMT gene causes an alteration in the enzyme activity, where the enzyme activity is reduced 4 times in genotypes related to low enzyme activity. In schizophrenic patients, alterations in the amounts and efficiency of dopamine are known to be related to the clinical symptoms and cognitive functions. This study aimed to investigate the effects of COMT Val158Met functional polymorphisms on clinical symptoms, executive functions related to prefrontal functions, and attention and verbal memory in schizophrenic patients. Method: Schizophrenic patients in remission, who were followed up at the Psychosis Clinics of Pamukkale University Faculty of Medicine, Department of Psychiatry between the years of 20072009, were included in the study. The Brief Psychiatric Rating Scale (BPRS), the Scale for Assessment of Positive Symptoms (SAPS), and theScale for Assessment of Negative Symptoms (SANS), were used to evaluate the patients. Neuropsychological evaluation included the Wisconsin Card Sorting Test (WCST) for executive functions, the Verbal Memory Processes Test (VMPT) for verbal memory and the Stroop Test (ST) for attention tasks. COMT enzyme Val158Met polymorphisms were defined from the isolated DNA of the patients by Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) analysis, as defined in literature. Results: A total of 42 patients (16 female, 26 male) were included in the study. The patients were grouped into high-level enzyme activity (Val/Val) and low-level enzyme activity (Val/Met and Met/Met) groups, according to their COMT Val158Met functional polymorphisms, and statistical analysis was carried out accordingly. Patients with Val/Val polymorphism had lower SANS scores, while the number of conceptual level responses, the percentage of conceptual level responses, and the failure to maintenance set scores at WCST were lower compared to those with the met allele. No difference was determined between the two groups in the scores on the SAPS and BPRS, and on the performance of the Stroop Test and the VPMT. Conclusion: We measured lower levels of negative symptoms in patients with high enzyme activity compared to those with low enzyme activity. There was no difference in executive functions assessed with the WCST in scores related to perseveration, while the patients with high enzyme activity presented a better performance in the fields related to working memory. Although the small subject number of the study represents a serious limitation, these results suggest that COMT Val158Met polymorphism has a limited effect on clinical symptoms and executive functions, but no effect on attention level and memory in schizophrenia.