Serum cytokine variations among inpatients with major depression, bipolar disorder, and schizophrenia versus healthy controls : a prospective ‘true-to-life’ study

Abstract

Background: There is increasing evidence of the association between chronic low-grade inflammation and severe mental illness (SMI). The objective of our study was to assess serum cytokine levels (SCLs) at admission and discharge in a true-to-life-setting population of inpatients with major depression (MD), bipolar disorder (BD), and schizophrenia (Sz), as well as of healthy controls. Methods: We considered MD, BD, and Sz to be SMIs. We evaluated 206 inpatients [MD, N=92; BD, N=26; mania (Ma), N=44; Sz, N=44). Generalized estimating equations were used to analyze variations in SCL [interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17] at hospital admission and discharge. Results of 100 healthy controls were compared with those of SMI patients at both time points. We evaluated patients’ improvement during in-hospital treatment in terms of general psychiatric symptoms, global clinical impression, functionality, and manic and depressive symptoms with validated scales. Results: In all, 68.9% of patients completed the study. Overall, SMI inpatients had higher SCL when compared with controls regardless of diagnosis. There was a significant decrease in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression–Severity Scale (CGI-S) scores, and an increase in Global Assessment of Functioning (GAF) scores for all disorders evaluated (p<0.001), as well as a significant decrease in HDRS-17 scores among MD inpatients (p<0.001) and in YMRS scores among Ma inpatients (p<0.001). IL-2 and IL-6 levels decreased significantly between admission and discharge only among MD inpatients (p=0.002 and p=0.03, respectively). We found no further statistically significant changes in SCL among the remaining disorders (BD, Ma, and Sz). There was no significant decrease in IFN-γ (p=0.64), TNF-α (p=0.87), IL-4 (p=0.21), IL-10 (p=0.88), and IL-17 (p=0.71) levels in any of the evaluated diagnoses. Conclusion: MD inpatients had a decrease in IL-2 and IL-6 levels during hospitalization, which was accompanied by clinical improvement. No associations were found for the remaining SMIs (BD, Ma, and Sz).