Serum cytokines-based biomarkers in the diagnosis and monitoring of therapeutic response in patients with major depressive disorder

Background: Several lines of evidence have suggested that cytokines are implicated in the pathophysiology of depression and antidepressant treatment outcome. However, the results are not always congruent and partly contradictory. We therefore examined the serum levels of multiple cytokines in patients with major depressive disorder (MDD), with the aim to identify serum cytokines-based biomarkers for MDD diagnosis and antide-pressant response.Methods: Fifty-nine patients with MDD and 61 healthy controls were included. The baseline levels of serum cytokines between MDD group and control group were compared, and the discriminative ability of different cytokines in predicting MDD patients from healthy controls was investigated using the receiver operating characteristic (ROC) curve method. The baseline levels of serum cytokines between antidepressant non-responders and responders were compared, and the discriminative ability of different cytokines in predicting nonresponders from responders was evaluated using the ROC curve method.Results: Compared to controls, 15 of the 37 serum cytokines were increased, while 8 cytokines were decreased in MDD patients (all P < 0.05). The results of ROC curve showed that the Area Under Curve (AUC) values of 15 cytokines including IL-2, IL-5, IL-6, IL-8, IL-12, IL-13, IL-16, CCL3, CCL4, CCL17, CXCL10, TNF-alpha, TNF-beta, VEGF-C, and FGF basic were greater than 0.7 in discriminating MDD patients from healthy control. Moreover, after 4-week treatment, levels of the 2 cytokines (IL-12 and TSLP) elevated at baseline significantly down-regulated, and levels of the 6 cytokines (IL-5, IL-16, CCL17, CXCL10, TNF-beta, and PIGF) decreased at baseline significantly up-regulated (all P < 0.05). Furthermore, a positive relationship was found between TNF-alpha levels and Hamilton Depression Rating Scale-24 (HAMD-24) scores in patients with MDD at baseline (r = 0.302, P = 0.019). Addi-tionally, compared to responders, nonresponders exhibited decreased levels of IL-1 alpha, IL-5, IL-13, IL-15, VEGF, and ICAM-1 (all P < 0.05). The ROC curve analysis demonstrated that a combined panel of IL-1 alpha, IL-5, and ICAM-1 achieved a high accuracy in discriminating antidepressant nonresponders from responders (AUC = 0.850, sensitivity = 83.3%, specificity = 81.8%).Conclusions: These results suggested that alterations in peripheral cytokines levels hold significant promise as biomarkers for MDD diagnosis and antidepressant response.