The Relationship Between Inflammatory Cytokines And Therapeutic Effect Of Bipolar Disorder With Acute Manic Episode

Background and Objective: Growing epidemiology research show that bipolar patients have a high incidence rate in autoimmune diseases, and patients with autoimmune diseases also have a high incidence rate in bipolar disorders. According to these phenomenon, more and more evidence suggests that immune dysfunction may be involved in the physiopathology of bipolar disorders. Patients with bipolar disorder trend to break out aggression, and meanwhile aggression is associated with immune dysfunction. The therapeutic effect of bipolar disorder is still unsatisfactory, but some research found the inflammatory cytokines of bipolar disorders would decrease after effective treatment. As typical first-line treatment, lithium and quetiapine, widely using in clinical work, serve to restore inflammation status. Thus, this study aimed to explore the relationship between inflammatory cytokines, especially regulatory factors, and treatment outcomes and aggression of bipolar disorder with acute manic episode.Methods: Forty-one patients of bipolar disorder with manic episode according to The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision(DSM-IV-TR) were enrolled in the present study after assessment with MiniInternational Neuropsychiatric Interview(MINI), and received combination treatment with quetiapine and lithium. The lithium blood levels reached effective therapeutic concentration(≥0.6 mmol/L) and quetiapine was gradually increased to the recommend dosage of 600-750 mg per day. Both medicines were maintained at the requisite levels for duration of this study. Blood samples and clinical data of patients were evaluated at baseline, 2nd week, 4th week and 8th week. A control group comprised of 36 age and gender matched healthy volunteers were enrolled, and their blood samples were assessed at the time of enrolment to provide a baseline. The plasma level of interleukin-17(IL-17), IL-23, IL-10, tumor necrosis factor α(TNF-α) and transforming growth factor β1(TGF-β1) were detected by avidinbiotincomplex enzyme-linked immunosorbent assay(ELISA). The Young mania rating scale was used to evaluate the severity of manic symptoms at the same time of detecting plasma levels. The results were analyzed by Student’s t test, Mann Whitney U test,Wilcoxon Signed Rank test,Pearson and Spearman correlation analysis. The last observation carried forward method(LOCF) was utilized to deal with cases where treatment discontinued prior to the end of treatment.Results: Thirty-four patients achieved response and twenty-six patients reached remission after 8th-week treatment. TGF-β1 and IL-23 plasma levels in patients were significantly higher than healthy controls at baseline(P<0.05), while the plasma levels of TNF-α, IL-10 and IL-17 had no significant difference between two groups(P>0.05). When comparing remitted patients with non-remitted patients, initial plasma level TGF-β1 was higher(P=0.029), while IL-23 was lower(P=0.035). The plasma levels of TNF-α, TGF-β1, IL-23 and IL-17 significantly decreased after treatment among the patients who continued through all 8 weeks of treatment and achieved response(P<0.05). The total scores and 9th-item scores of Young Mania Rating Scale(YMRS) gradually decreased during the treatment. The plasma levels of TNF-α, TGF-β1, IL-23 and IL-17 were significantly related to the total scores and 9th-item scores of YMRS at baseline(P<0.05), nevertheless IL-10 plasma level showed no correlation with the total scores and 9th-item scores of YMRS(P>0.05).Limitations: The relatively small sample size in patients and control groups should be considered as a limitation of the study.Conclusions: The physiopathology of bipolar disorder was associated with upregulated of inflammatory cytokines, mainly involving in dysfunction of cellular immunity and autoimmunity. The high initial plasma level of TGF-β1 and low initial plasma level of IL-23 indicated better prognosis during combination treatment with quetiapine and lithium in manic patients. The trend of decreasing plasma levels of TNF-α, TGF-β1, IL-23 and IL-17 indicated therapeutic effect. The plasma level of TNF-α, TGF-β1, IL-23 and IL-17 were related to the severity of manic symptoms at baseline, especially aggression symptom. The severity of manic and aggression symptoms improved much more quickly than dysfunction of inflammation status.