Neurocognitive deficits in schizophrenia and polymorphic variants of protein kinase signaling pathway genes: search for associations

Aim. To study the associations of polymorphic variants in the BDNF, GSK3B, AKT1, MAPK, and CREB1 genes with neurocognitive deficits (NCD) in patients with schizophrenia.

Materials and methods. The study included 148 patients with schizophrenia, who underwent psychometric examination and genotyping. The Brief Assessment of Cognition in Schizophrenia (BACS) was used to assess neurocognitive functioning indicators. Ten polymorphic variants in the genes BDNF, GSK3B, AKT1, MAPK, and CREB1 were genotyped. Statistical processing was carried out using the χ2 goodness-of-fit test, Fisher’s exact test, cluster analysis, the Kruskal-Wallis test, and multivariate analysis of variance.

Results. The CT genotype of the BDNF rs6265 polymorphic variant was more common in the group of patients with severe NCD, while the CC genotype was more typical for patients with moderate and mild NCD. In patients with severe and moderate NCD, the AG MAPK rs8136867 genotype was predominant, while in patients with mild NCD, the GG genotype was predominant. A statistically significant effect of polymorphic variants of the BDNF gene on performance in the Token motor task (rs6265: p = 0.025 and rs11030104: p = 0.027) and the Tower of London subtests (rs6265: p = 0.016 and rs11030104: p = 0.037) was found. There was also a significant effect of MAPK gene polymorphisms on the performance in the Token motor task subtest (rs8136867: p = 0.003) and CREB1 on the Tower of London test (rs6740584: p = 0.022).

Conclusion. For the first time, associations of BDNF rs6265 and MAPK rs8136867 polymorphisms with neurocognitive deficit in patients with schizophrenia, as well as BDNF rs6265, BDNF rs11030104, MAPK rs8136867, and CREB1 rs6740584 polymorphisms with performance in the BACS battery subtests were found.

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