The Role of the Interaction between the NMDA and Dopamine Receptor Genes in Impaired Recognition of Emotional Expression in Schizophrenia
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Objectives. To seek the genetic mechanisms of impairments to the recognition of emotions, which is a sign of schizophrenia which degrades social adaptation of patients. This search was based on the view that the interaction between the dopaminergic and glutamatergic systems has a role in the pathogenesis of schizophrenia. The effects of the interaction between the polymorphic C366G locus in the gene encoding the NR2B subunit of the NMDA receptor – GRIN2B – the polymorphic loci in the dopamine receptor genes ANKK1/DRD2 Taq1A and DRD4 48-VNTR on the recognition of emotional expressions were studied. Materials and methods. The effects of the interaction between GRIN2B and DRD2 were studied in cohorts of 237 patients and 235 healthy subjects; those between GRIN2B and DRD4 were studied in cohorts of 268 and 208, respectively. Results and conclusions. Both effects reached significance in the combined cohorts of patients and healthy subjects (GRIN2B × DRD2, F = 4.12, p = 0.043; GRIN2B × DRD4, F = 6.43, p = 0.012). The effect of the interaction between the polymorphic loci in the GRIN2B and DRD2 genes on the recognition of expressed emotions in schizophrenia patients was confirmed. In patients with the less effective allele of the DRD2 gene and not bearing the minor allele of the GRIN2B gene, results were close to normal, while the genotype containing the minor alleles of both genes produced the worst results. This result is consistent with concepts of the possible role of the hypofunction of NMDA receptors and D2-mediated regulation of their activity in the production of schizophrenia endotypes such as the recognition of expressed emotions.
KeywordsGRIN2B DRD2 DRD4 recognition of emotions epistatic effects psychosis
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