Cognitive impairment in patients with treatment resistant schizophrenia: Associations with DRD2, DRD3, HTR2A, BDNF and CYP2D6 genetic polymorphisms

Abstract

Introduction

According to various data, 25–50% of all patients with schizophrenia suffer from treatment resistance. It is believed that patients with treatment-resistant schizophrenia (TRS) have reduced cognitive skills, compared to the patients with a more favourable type of schizophrenia. However, according to some authors, there is limited evidence-based research on this topic at present.

Materials and methods

The total number of patients included 130 patients with a diagnosis of schizophrenia (F20 according to ICD 10). All patients were examined according to the following scales: Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), Brief Assessment of Cognition in Schizophrenia (BACS).

Results

Our results showed that patients with TRS as a whole had worse cognitive functions than nTRS patients (p = 0.357). In the group of patients with TRS, polymorphism CYP2D6*4 showed an effect on executive functions. Carriers of the heterozygous GA genotype had higher values of executive functions (p = 0.043). No association between the studied gene polymorphic variants and TRS was found in this research.

Conclusion

The polymorphic variant CYP2D6*4 showed an effect on cognitive function in the TRS group, regardless of their mental state and the effect of pharmacotherapy. In the future, it will be necessary to conduct larger prospective studies with a greater number of patients and a greater number of polymorphic variants of genes. Further identification of genetic predictors of cognitive impairment will improve researchers’ understanding of their causes and possibly move closer to more targeted therapy for schizophrenia.