Study of the Effect of Interaction between Traumatic Brain Injury and Functional Polymorphisms of Interleukin Genes on the Severity of Schizophrenia

Abstract— The aim of the study was to assess the associations between traumatic brain injury (TBI) and severity of symptoms in patients with schizophrenia, taking into account the modulating influence of polymorphisms of pro- and anti-inflammatory interleukins genes. The study included 1157 patients with schizophrenia (ICD-10 items F20, F21, F23.1, F25). In the study, 452 patients had a history of TBI, and 538 patients denied having TBI. The severity of schizophrenia symptoms was measured using the PANSS. Three polymorphisms located in the promoters of the genes encoding interleukins IL-1β rs16944 IL4 rs2243250 and IL10 rs2243250 were selected for the genetic study. A mutual effect of TBI and the interleukin gene variants IL-4 (C-589T) rs2243250 and IL-10 (C-592A) rs1800872 on the severity of schizophrenia symptoms was found. In particular, in the group of CC IL-4 (C-589T) genotype carriers, the severity of negative and general psychopathological symptoms was higher than in carriers of the T allele. The IL-10 (C-592A) rs1800872 polymorphism modified the effect of TBI on general psychopathological symptoms, but not positive or negative symptoms of schizophrenia. The severity of these symptoms was higher in carriers of the CC genotype compared to carriers of the A allele. In patients without TBI, the polymorphisms did not have a significant effect on the phenotype. Thus, our study has shown for the first time that the presence of a history of TBI and the patient’s genetic characteristics negatively affect the severity of schizophrenia.