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<p><b>Objective.</b> To evaluate the roles of the rs1800795 polymorphism of the <i>IL6</i> gene encoding interleukin-6 in the decline in cognitive functions after the onset of schizophrenia and in modifying the association between adverse childhood experiences (ACE) and cognitive deficit in patients. <b>Materials and methods.</b> The cohort consisted of 530 patients aged 18–45 years with diagnoses of schizophrenia and schizoaffective and acute psychotic disorder with moderate to high cognitive premorbidity. All participants underwent cognitive testing to assess information processing speed, episodic and working verbal memory, and executive functions. Each participant’s genotype at the rs1800795 site of the <i>IL6</i> gene was determined. Information on patients’ ACE and premorbid cognitive level (PCL) was obtained by analysis of case histories. <b>Results.</b> The interaction of genotype, ACE, and sex was found to have a significant effect on the extent of decline in current cognitive functioning from that expected based on PCL (F = 8.44; <i>p</i> = 0.004; η<sup>2</sup><sub><i>p</i></sub> = 0.02): cognitive functioning in the group of women with ACE was lower in carriers of the C allele than in the GG homozygotes. <b>Conclusions.</b> The results obtained here identify an unfavorable effect of the <i>IL6</i> C allele, which is associated with increased interleukin-6 production, on cognitive functions in schizophrenia, which is consistent with the hypothesis of a proinflammatory immune profile as a component of the pathogenesis of the disorder, and that sex and ACE have important modifying roles in the association of the <i>IL6</i> gene with cognitive deficit in patients.</p>

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The Role of the rs1800795 Polymorphism of the Interleukin 6 Gene in the Development of Cognitive Deficit Associated with Schizophrenia

  • 期刊论文

  • 发表日期：

    2026年3月16日

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  • M. V. Alfimova,
  • M. V. Gabaeva,
  • T. V. Lezheiko,
  • V. V. Plakunova,
  • V. E. Golimbet

摘要

Objective. To evaluate the roles of the rs1800795 polymorphism of the IL6 gene encoding interleukin-6 in the decline in cognitive functions after the onset of schizophrenia and in modifying the association between adverse childhood experiences (ACE) and cognitive deficit in patients. Materials and methods. The cohort consisted of 530 patients aged 18–45 years with diagnoses of schizophrenia and schizoaffective and acute psychotic disorder with moderate to high cognitive premorbidity. All participants underwent cognitive testing to assess information processing speed, episodic and working verbal memory, and executive functions. Each participant’s genotype at the rs1800795 site of the IL6 gene was determined. Information on patients’ ACE and premorbid cognitive level (PCL) was obtained by analysis of case histories. Results. The interaction of genotype, ACE, and sex was found to have a significant effect on the extent of decline in current cognitive functioning from that expected based on PCL (F = 8.44; p = 0.004; η2p = 0.02): cognitive functioning in the group of women with ACE was lower in carriers of the C allele than in the GG homozygotes. Conclusions. The results obtained here identify an unfavorable effect of the IL6 C allele, which is associated with increased interleukin-6 production, on cognitive functions in schizophrenia, which is consistent with the hypothesis of a proinflammatory immune profile as a component of the pathogenesis of the disorder, and that sex and ACE have important modifying roles in the association of the IL6 gene with cognitive deficit in patients.