Serum level of soluble interleukin 6 receptor is a useful biomarker for identification of treatment-resistant major depressive disorder

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Abstract
Aim A substantial proportion of major depressive disorder patients are treatment-resistant to antidepressant therapy, who require augmentation drugs, or other treatments including electroconvulsive therapy or transcranial magnetic stimulation. Identifying treatment-resistant major depressive disorder patients before the actual administration of antidepressant is, however, often difficult. Accordingly, the serum biomarker to identify treatment-resistant patients will be helpful in clinical settings. This study aims to clarify the appropriate biomarkers for identification of treatment-resistant major depressive disorder. Method Given that immune-inflammatory processes are involved in the pathogenesis of major depressive disorder, it is possible that certain cytokine-related molecules could serve as clinically useful biomarkers of treatment-resistant major depressive disorder patients. In this study, we measured serum levels of tumor necrosis factor-alpha, interleukin 6, and soluble interleukin 6 receptor after major depressive disorder patients underwent antidepressant therapy. Results The serum level of soluble interleukin 6 receptor, but not interleukin 6 or tumor necrosis factor-alpha, was significantly higher in treatment-resistant major depressive disorder patients than in remitted patients, suggesting that serum soluble interleukin 6 receptor could be a good biomarker of treatment-resistant major depressive disorder. Receiver operating characteristic analysis confirmed that serum soluble interleukin-6 receptor level measurement was useful for identification of treatment-resistant major depressive disorder patients. Multiple regression analysis using the serum levels of the aforementioned cytokines as explanatory variables and the Quick Inventory of Depressive Symptomatology-Self Report score (QIDS-SR16) as a target variable showed that only serum soluble interleukin-6 receptor level could explain the severity of major depressive disorder. Conclusion Based on these results, we recommend measurement of serum soluble interleukin-6 receptor level to discriminate treatment-resistant major depressive disorder patients. High serum soluble interleukin-6 receptor level is associated with the pathogenesis of treatment-resistant major depressive disorder, suggesting the involvement of the interleukin 6 trans-signaling system in onset of treatment-resistant major depressive disorder.

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