Chemokine receptor 4 expression on blood T lymphocytes predicts severity of major depressive disorder.

Background: Chemokines and their receptors regulate inflammatory processes in major depressive disorder (MDD). Here, we characterize the expression pattern of the C-C chemokine receptor 4 (CCR4) and its ligands CCL17 and CCL22 in MDD and its clinical relevance in predicting disease severity.

Methods: Expression of CCR4 on peripheral blood lymphocytes and serum CCL17/CCL22 levels were measured using multiparameter flow cytometry and multiplex assays in 33 depressed inpatients at baseline (T0) and after 6-week multimodal treatment (T1) compared with 21 healthy controls (HC). Using stratified and correlation analysis, we examined the associations of CCR4-CCL17/CCL22 expression with depression severity and symptoms according to standard clinical rating scales and questionnaires. Additionally, we assessed whether polygenic risk score (PRS) for psychiatric disorders and chronotype are associated with disease status or CCR4-CCL17/CCL22 expression. Regression analysis was performed to assess the capacity of CCR4 and PRS in predicting disease severity.

Results: Compared with HC, MDD patients showed significantly decreased CCR4 expression on T cells (T0 and T1), whereas CCL17/CCL22 serum levels were increased. Stratified and correlation analysis revealed an association of CCR4 expression on CD4 T cells with depression severity as well as Beck Depression Inventory-II items including loss of pleasure, agitation and cognitive deficits. CCR4 expression levels on CD4 T cells together with cross-disorder and chronotype PRS significantly predicted disease severity.

Limitations: This exploratory study with small sample size warrants future studies.

Conclusions: This newly identified CCR4-CCL17/CCL22 signature and its predictive capacity for MDD severity suggest its potential functional involvement in the pathophysiology of MDD.