Chemokines and their receptors “influence neuroendocrine signaling, neurotransmission, and interaction between neurons and microglia and have therefore been suggested to be involved in the pathophysiology of MDD and depression-like behavior,” but their potential as a predictor of disease severity has not been explored, Jana Freff, a PhD candidate at the University of Münster (Germany), and colleagues wrote.
Recent research has identified disease-associated single-nucleotide polymorphisms that can be used to calculate a cumulative polygenic risk score (PRS) for an individual, they said. “While PRS only explain a small proportion of the phenotypic variance, they provide a valuable tool to study the influence of common genetic factors in complex disorders, such as MDD.”
In a study published in the Journal of Affective Disorders , the researchers identified 33 adult inpatients with MDD and 21 healthy controls. Blood samples were collected at the time of inpatient admission and after 6 weeks of treatment. MDD severity was measured using the Hamilton Rating Scale for Depression and Inventory of Depressive Symptomatology. Chemokine receptor 4 (CCR4) was measured using mean fluorescence intensity (MFI).
The MDD patients showed significant decreases in CCR4 expression on CD4+ T cells; these patients also had elevated serum levels of the ligands CLL17 and CLL22, compared with healthy controls.
The researchers examined the relationship between CCR4 expression on T cells and MDD severity. Individuals with severe depression had lower levels of CCR4 on CD4+ T cells, compared with nondepressed or mildly depressed individuals.
CCR4 expression also was significantly associated with several somatic and cognitive-affective items on the Beck Depression Inventory II including loss of pleasure (P < .05), agitation (P < .01), and difficulty concentrating (P < .05). “In addition, the total score of BDI-II correlated negatively with the CCR4 MFI (P < .05) emphasizing that greater MDD severity is associated with lower CCR4 expression on CD4+ T cells,” the researchers said.
The researchers also assessed the predictive value of immune parameters and PRS for MDD severity. They did not find significant correlations between PRS and these parameters; however, “including PRS for a cross-disorder phenotype and chronotype could improve the predictive performance of immune parameters on MDD severity,” and genetic data should be considered in future studies.
The study findings were limited mainly by the small size, the researchers noted. Additional studies with larger patient populations are needed, not only to investigate the functional role of CCR4 in MDD, and the association between CCR4 and remission or treatment resistance, but also the impact of genetic factors on MDD status, they said.
However, the results of the current study show an altered expression of CCR4 in MDD, and “Future augmented strategies to treat depression may therefore target CCR4 specifically on CD4+ T cells,” they concluded.
The study was funded in part by grants to several coauthors from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy. Ms. Freff had no financial conflicts to disclose.