Abstract
BackgroundSchizophrenia is a common mental illness whose pathogenesis is still unknown. The vulnerability and stress model in schizophrenia assume that susceptibility to the disease is mainly associated with genes. Of the five symptomatic dimensions of schizophrenia, cognitive impairment appears to be most associated with the pathogenesis of schizophrenia. The aim of the study was to explore whether selected nucleotide variants in GRIN1, GRIN2A, and GRIN2B encoding subunits of the N-methyl-d-aspartate receptor (NMDA-R) receptor occur in a selected group of patients with treatment resistant schizophrenia with cognitive impairment.MethodsThe study included 45 patients diagnosed with super refractory schizophrenia, all with cognitive deficits and chronically psychotic. DNA fragments including the studied polymorphisms of the NMDA receptors subunit genes were amplified by polymerase chain reaction and subjected to sequencing.ResultsThe study did not confirm the presence of any of the four selected single-nucleotide variants in GRIN1, GRIN2A, and GRIN2B subunits of NMDA-R in the study group.ConclusionResults of the study indicated that the selected single-nucleotide variants are not associated both with resistance to clozapine and the presence of cognitive deficits inschizophrenia. It is possible, however, that a more extensive sequencing along with analyzing the expression of these genes may reveal different single-nucleotide variants than those assumed in the study.
Highlights
Due to the unknown pathogenesis of schizophrenia, its treatment still faces great difficulties
Sequencing of the DNA fragments from schizophrenic patients and healthy control group was conducted to search for a polymorphism in the gene subunit GRIN1 associated with susceptibility to schizophrenia, GRIN2B associated with the efficacy of neuroleptic and polymorphisms in genes of subunits, which determine NMDA receptor functions—GRIN2A [2304–2306 (AAT)] and GRIN2B—2055–2057 (AAC)
singlenucleotide variants (SNVs) rs56069446 was found in the intron 8 of the GRIN2B gene, present in one healthy person in the control group and two people with non-remission schizophrenia (Fig. 2)
Summary
Due to the unknown pathogenesis of schizophrenia, its treatment still faces great difficulties. The aim of the study was to explore whether selected nucleotide variants in GRIN1, GRIN2A, and GRIN2B encoding subunits of the N-methyl-d-aspartate receptor (NMDA-R) receptor occur in a selected group of patients with treatment resistant schizophrenia with cognitive impairment. Conclusion Results of the study indicated that the selected single-nucleotide variants are not associated both with resistance to clozapine and the presence of cognitive deficits in schizophrenia. It is possible, that a more extensive sequencing along with analyzing the expression of these genes may reveal different single-nucleotide variants than those assumed in the study
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