Effect of genetic polymorphism of interleukin production on the association of adverse childhood experiences with cognitive functions in schizophrenia

Background. Adverse childhood experiences (ACEs) are known to increase the risk of schizophrenia. One putative mechanism of the ACEs’ influence on the disease is an increased activation of the immune system. Thus, genetic polymorphism of the immune system may cause variability in disease manifestations, including cognitive deficits, which is important to consider in the prevention and treatment of psychosis.

Aim: to assess the effect of genetically determined characteristics of interleukin production on the relations between ACEs and cognitive deficit in patients.

Methods. The sample included 203 schizophrenia patients aged 16–45 years who completed tests of verbal fluency (VF) and attention/ working memory. The presence of ACEs, polygenic risk scores (PRS) of the concentration of proinflammatory interleukins (IL-6, IL-8, IL-18, IL-27) and a multigenic risk score (MGS) of the deleteriousness impact of mutations in the genes of regulatory interleukins (IL-2, IL-4, IL-10, IL-13) were assessed for each participant. The moderation effect of genetic variables on the association between ACEs and cognition was evaluated with covariance analysis, controlling for sex, schizophrenia PRS, intelligence PRS, and two ancestry-related principal components.

Results. The IL6-PRS was a moderator of the association between ACEs and VF. The unfavorable influence of high IL6-PRS on VF took place in women with ACEs. IL8-PRS and MGS associated with cognition regardless of ACEs.

Conclusion. The results confirm the hypothesis of a negative effect of genetic polymorphism leading to an increase in IL-6 concentration on the cognitive functions of schizophrenia patients with ACEs and indicate that the effect is sex-specific.

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