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

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-?, 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-?, 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.

SUBMITTER: Yamasaki K

PROVIDER: S-EPMC7722658 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Yamasaki Katsuhiko K Hasegawa Tomonori T Takeda Masatoshi M

Neuropsychopharmacology reports 20200312 2

<h4>Aim</h4>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 clinica ...[more]

PMID: 32162496

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Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Dataset Information

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

Publications

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

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