Cognitive function dynamics during folate augmented therapy in patients with schizophrenia carrying MTHFR677C>T gene polymorphism: A pilot study

Abstract

The aim of the investigation is to study the carriage of the alleles of folate cycle MTHFR677C>T polymorphism and to assess cognitive function dynamics in the course of folate augmented antipsychotic therapy in schizophrenic patients carrying defective MTHFR677T allele. Materials and Methods. 129 patients with schizophrenia underwent molecular diagnosing of 677C>T polymorphism in MTHFR folate metabolism gene using PCR method with allele-specific primers and the following on-line detection. Of them 18 patients carrying defective T allele received antipsychotic therapy augmented by folates. The patients were tested with a standard battery of cognitive tests before and after augmentation. Patients of the control group (n=13) comparable with the main one in gender, age, psychic condition were subject to the same procedures, but did not receive folates. The level of plasma homocysteine was determined in 7 patients. Results. Carriage of defective T allele of MTHFR677C>T polymorphism was found in more than half the examined patients, more often than in the general population, though being not statistically significant for such a quantity of observations. Improvement of cognitive functioning was noted in those having defective T allele and receiving folates: short-term auditory memory (p<0.05), phonetic verbal fluency (p<0.05), problemsolving behavior (p<0.05), visual-motor coordination (p<0.01), rigidity (p<0.05), motor velocity (p<0.05), working memory, attention selectivity and distribution (p<0.05). The cognitive function dynamics was more pronounced in the main group than in the control one, however in somepatients exacerbation of productive symptoms was observed. Augmentation by folates was most effective in patients with homozygous carriage of the defective T allele and hyperhomocysteinemia before intervention. Conclusion. Augmentation of antipsychotic therapy by folates may appear to be a promising strategy for imp roving cognitive functions in patient with schizophrenia having folate metabolism impairments, which requires personified approach with biomarker study before intervention.