Immune factors associated with prominent negative symptoms and disease severity in schizophrenia

Schizophrenia is a severely disabling and clinically heterogeneous disease that manifests with disorders of thinking, motivation and emotions. Negative symptoms of schizophrenia include decreased expression of emotions, poverty of speech, withdrawal from social contacts, anhedonia. They poorly respond to therapy, and their severity has the most significant impact on the functioning and quality of life of patients. Changes in systemic immunity in schizophrenia with pronounced negative symptoms are poorly studied. We have previously shown the relationship of elevated levels of interleukin-10 (IL-10) with the severity of negative symptoms and with morphometric changes in the brain in schizophrenia. The aim of this study was to investigate the relationship of a number of systemic immunity parameters (regulatory and proinflammatory cytokines and indicators of cell immunity) with the severity of negative symptoms and the disease severity in schizophrenia. The study included 94 patients treated in the Psychiatric Clinical Hospital No. 1 named after N.A. Alekseev, 66 of whom had pronounced negative symptoms. The control group consisted of 24 healthy volunteers. ELISA and multiplex analysis were used to determine cytokine levels, and multicolour flow cytometry was used to determine the parameters of cellular immunity. The level of circulating immune complexes was determined by immune turbodimetric analysis. Differences were considered statistically significant at p < 0.05. The results of the study showed that the majority of schizophrenia patients, regardless of the severity of negative symptoms, had an increase in the levels of cytokine IL-8. It was shown that the severity of negative symptoms was associated with increased levels of cytokines IL-10, IL-12p40, IL-17E/IL-25 and IL-34. It was also revealed that patients with pronounced negative symptoms had a higher level of CD3^-CD19^-B cells compared to the control group, which, taking into account the changes of the cytokine profile, indicate possible activation of the B cell link of humoral immunity. The data obtained in this work indicate that in schizophrenia with pronounced negative symptoms and severe course of the disease, there is activation of immunoregulatory and Th2-mechanisms. The results contribute to the understanding of the role of immunity disorders in the pathogenesis of various clinical forms of schizophrenia.