A Matched Case-Control Study of the Serum Level and Gene Expression of IL-6 and IL-12 in Patients with Schizophrenia Spectrum Disorder: An Azeri Acute Phase/Recent-Onset Psychosis Survey (ARAS) Study

Background: The causes of schizophrenia spectrum disorders are believed to be multifactorial, with both genetic and environmental factors, as well as gene-environment interactions, influencing the course of this disorder. Research suggests that immunological factors may play a role in the development of psychotic disorders. Objectives: The aim of this study is to evaluate and compare the serum levels of interleukin-6 (IL-6) and interleukin-12 (IL-12), as well as the expression levels of IL-6 and IL-12 genes, between an Iranian Azeri population of patients with first-episode psychosis and healthy controls. Methods: Forty patients who had recently experienced first-episode non-affective psychosis were allocated to the patient group. Forty healthy volunteers, matched for age and gender, were also recruited as controls. The study was conducted in 2020 in Tabriz, Iran. Peripheral blood samples were collected (using the Ficoll-Paque process) and assessed to determine the expression levels of IL-6 and IL-12 mRNA (using real-time Polymerase Chain Reaction-PCR- system), as well as the serum levels of IL-6 and IL-12 (with a sandwich ELISA kit). GraphPad Prism Version 6.0 was used for all statistical analyses. Results: Each group consisted of 40 participants in this study. Patients had significantly higher levels of IL-6 mRNA expression compared to the healthy controls (P < 0.0001), while no significant difference was found between the two groups in terms of IL-12 mRNA expression (P = 0.5697). A similar pattern was reported for the serum levels of IL-6 (P < 0.0001) and IL-12 (P = 0.0777). The area under the curve (AUC), which indicates the accuracy of the predictive model, was 0.9669 for the level of IL-6 mRNA expression (P < 0.0001). This Area (AUC) was 0.9584 for the serum concentration of IL-6 (P < 0.0001). The levels of IL-6 or IL-12 were not correlated with the severity of symptoms, gender, or age of the patients. Conclusions: The expression level of IL-6 mRNA and the serum concentration of IL-6 were altered in patients with first-episode non-affective psychosis. This finding supports the role of inflammatory pathways in the pathogenesis of psychosis. According to our results, measurement of the circulating level of IL-6 may be useful in distinguishing patients with first-episode psychosis from healthy individuals.