Remission and Immunological Profile of Patients in the Initial Stages of Schizophrenia

Aim. To study the types of remission and levels of peripheral inflammatory cytokines as potential biomarkers of remission in patients at the early stages of schizophrenia.

Design. A naturalistic study.

Materials and methods. Forty-eight patients (25 women and 23 men) were examined at the initial stages of schizophrenia during the period of remission (age — 28.3 ± 5.8 years). The duration of the disease was 2.7 ± 1.3 years, the average age of disease onset — 25.8 ± 5.5 years. The average number of relapses reached 1.8 ± 0.7. 19 (40%) of patients had one psychotic episode in their anamnesis, 24 (50%) — two, 5 (10%) — three. The control group included 86 people, 38 men and 48 women, aged 18 to 30 years without mental, autoimmune disorders, exacerbation of chronic somatic diseases (standard relatively healthy group, the level of proinflammatory cytokines in participants tended to zero). The study used a clinical and psychopathological method and a standardized assessment using the Positive and Negative Syndrome Scale (PANSS).

Results. The average duration of remission was 11.4 months. In the early stages of schizophrenia, the paranoid type of remission was predominant (48%). The thymopathic type of remission occurred in 18% of cases, apathetic and hypochondriacal — 10% each, pseudopsychopathic — in 8%, asthenic — in 6%. General psychopathological symptoms were most pronounced in hypochondriacal, residual negative symptoms — in the apathetic type of remission. In the hypochondriacal type, the severity of positive and negative symptoms did not differ, and in the paranoid type, residual positive symptoms prevailed over negative ones. The thymopathic type of remission was distinguished by the least severity of residual symptoms. In 70% of patients in the early stages of schizophrenia, a significant increase in blood cytokine levels was found compared to those in the control group. The levels of interleukins (IL) 6, IL-9, IL-10, IL-13, IL-22, tumor necrosis factor α, CCL20/MIP3-α increased to the greatest extent (p = 0.001). The level of IL-22 correlated with the total PANSS score (r = –0.52; p = 0.008), and the level of IL-6 — with the composite PANSS index (the difference between the sum of the scores of positive and negative symptoms) (r = 0.46; p = 0.022). The strongest cytokine reaction was observed in the paranoid and pseudopsychopathic variants due to an increase in the content of IL-6, IL-33 and IL-13. The longer the duration of the present remission, the lower were the levels of IL-33 (r = –0.45; p = 0.023), IL-17A (r = –0.40; p = 0.049), IL-17F (r = –0.59; p = 0.002).

Conclusion. The available data indicate an important role of cytokines in the development of schizophrenia. The presented results may have prognostic value for assessing the stability of remission, the studied cytokines — serve as potential biomarkers of schizophrenia remission and therapeutic targets for pathogenetic therapy.

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