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Genetic Polymorphism of Cytokines IL-1β, IL-4, and TNF-α as a Factor Modifying the Influence of Adverse Childhood Experiences on the Symptoms of Schizophrenia

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Objectives. Working from the hypothesis that activation of the immune system is one of the mechanisms whereby early environmental factors influence the onset and course of schizophrenia, we studied the effects of the interaction of adverse childhood experiences (ACE) and genotypes at the polymorphic loci rs16944 of the IL1B gene, rs2243250 of the IL4 gene, and rs1800629 of the TNF-α gene on the severity of different groups of schizophrenia symptoms. Materials and methods. The cohort consisted of 546 patients with schizophrenia spectrum disorders. ACE was detected by analysis of medical records and a questionnaire completed by the patients. A five-factor Positive and Negative Syndrome Scale (PANSS) model with a built-in two-factor model of the negative syndrome was used. Results. The interaction of ACE and TNF-α was found to have a significant effect on the cognitive disorganization factor after adjusting for multiple comparisons, with discrimination of carriers of different genotypes in the group without ACE (pFDR < 0.018; \( {\upeta}_p^2 \) = 0.03). The interaction of ACE and genotype was found to have a significant effect on the cognitive disorganization syndrome (F = 5.87; p = 0.003; \( {\upeta}_p^3 \) = 0.03). Stereotyped thinking and volitional disorder identified on the PANSS showed the strongest correlations with the cognitive disorganization factor (ro = 0.84 and ro = 0.82, respectively) and the most significant differences depending on the interaction of genotype and ACE (Kruskal–Wallis test, H = 12.28, p = 0.006 and H = 12.79, p = 0.005, respectively). Conclusions. ACE modifies the relationship between the pathogenesis of schizophrenia and the rs1800629 polymorphic locus located in the TNF-α gene promoter, which is also an enhancer of 60 more genes located in the major histocompatibility complex.

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Authors and Affiliations

  1. Mental Health Research Center, Moscow, Russia

    M. V. Alfimova, G. I. Korovaitseva, M. V. Gabaeva, V. V. Plakunova, T. V. Lezheiko & V. E. Golimbet

  2. Alekseev Psychiatric Clinical Hospital No. 1, Moscow Health Department, Moscow, Russia

    M. V. Alfimova

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  1. M. V. Alfimova
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  2. G. I. Korovaitseva
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  3. M. V. Gabaeva
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  4. V. V. Plakunova
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  5. T. V. Lezheiko
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  6. V. E. Golimbet
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Correspondence to M. V. Alfimova.

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Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 122, No. 9, pp. 110–117, September, 2022.

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Alfimova, M.V., Korovaitseva, G.I., Gabaeva, M.V. et al. Genetic Polymorphism of Cytokines IL-1β, IL-4, and TNF-α as a Factor Modifying the Influence of Adverse Childhood Experiences on the Symptoms of Schizophrenia. Neurosci Behav Physi 53, 524–530 (2023). https://doi.org/10.1007/s11055-023-01451-3

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