Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 2025
[The role of the rs1800795 polymorphism of the interleukin 6 gene in the development of cognitive deficits associated with schizophrenia].
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Alfimova M V, Gabaeva M V, Lezheiko T V, Plakunova V V, Golimbet V E
Аннотация
OBJECTIVE: To evaluate the role of the rs1800795 polymorphism in the IL6 gene encoding interleukin-6 in reducing cognitive functioning after the onset of schizophrenia and in modifying the association between adverse childhood experiences (ACEs) and cognitive deficits in patients.
MATERIAL AND METHODS: The sample consisted of 530 patients diagnosed with schizophrenia, schizoaffective disorder, and acute psychotic disorder, aged 18-45 years, with moderate or high cognitive premorbidities. All participants underwent cognitive testing to assess processing speed, episodic and working verbal memory, and regulatory functions. Each patient was genotyped at the rs1800795 site of the IL6 gene. Information on ACE and the cognitive premorbid level (CPL) of patients was obtained through a review of case histories.
RESULTS: A significant effect of the interaction of genotype, ACE, and gender on the decrease in current cognitive functioning from the expected one based on CPL (F=8.44; p=0.004; η²p=0.02) was found: in the group of women with ACE, cognitive functioning was lower in carriers of the C allele compared to GG homozygotes.
CONCLUSION: The results indicate an adverse impact of the IL6 C allele associated with increased interleukin-6 production on cognitive functions in patients with schizophrenia, which is consistent with the hypothesis of a pro-inflammatory immune profile as one of the components of the disease pathogenesis, and on the important modifying role of sex and ACE in the association of the IL6 gene with the cognitive deficit of patients.
MATERIAL AND METHODS: The sample consisted of 530 patients diagnosed with schizophrenia, schizoaffective disorder, and acute psychotic disorder, aged 18-45 years, with moderate or high cognitive premorbidities. All participants underwent cognitive testing to assess processing speed, episodic and working verbal memory, and regulatory functions. Each patient was genotyped at the rs1800795 site of the IL6 gene. Information on ACE and the cognitive premorbid level (CPL) of patients was obtained through a review of case histories.
RESULTS: A significant effect of the interaction of genotype, ACE, and gender on the decrease in current cognitive functioning from the expected one based on CPL (F=8.44; p=0.004; η²p=0.02) was found: in the group of women with ACE, cognitive functioning was lower in carriers of the C allele compared to GG homozygotes.
CONCLUSION: The results indicate an adverse impact of the IL6 C allele associated with increased interleukin-6 production on cognitive functions in patients with schizophrenia, which is consistent with the hypothesis of a pro-inflammatory immune profile as one of the components of the disease pathogenesis, and on the important modifying role of sex and ACE in the association of the IL6 gene with the cognitive deficit of patients.