In this study, we identified the CD4+/CD8 + T cell ratio, albumin level and M% as three laboratory parameters significantly associated with the severity of MDD. On the basis of these three factors, we constructed a novel joint index that showed a good performance in discriminating disease severity, and we validated our findings in the validation cohort.
MDD is a prominent public health concern worldwide and approximately 6% of adults experience MDD per year [30]. Moreover, patients with MDD show an increased risk of the occurrence of several comorbidities, including diabetes mellitus and cardiovascular and cerebrovascular diseases, which further increase the disease burden [31]. MDD can also lead to death by suicide. Thus, early diagnosis and accurate classification of MDD can help clinicians design appropriate treatment strategies for patients and reduce the disease burden and death. In clinical practice, biomarkers from laboratory examinations are more sensitive and objective, which would facilitable accurate classification of the severity of MDD.
In the present study, we found that the CD4+/CD8 + T cell ratio and albumin concentration of patients with mild and moderate depressive disorder were significantly higher than those of patients with severe depressive disorder, while the M% of patients with mild and moderate depressive disorder was significantly lower than that of patients with MDD. A number of studies have demonstrated that changes in immune function may play an important role in the disease process of depressive disorder. Dysregulation of the hypothalamic-pituitary adrenal axis is a hallmark of depressive disorder, which results in the hypersecretion of cortisol and exerts inhibitory effects on the immune system by suppressing the cellular immune response and increasing inflammatory cytokines [32]. A previous study investigated the specific alterations in the lymphocyte subsets of patients with MDD and found that the level of CD8 + T cells in these patients was higher than that in the healthy control population [33]. In addition, another study showed that cortisol could increase the concentration of serum soluble CD8 or suppressor/cytotoxic antigen to suppress the immune response of patients with depressive disorder [34]. These results indicated that depressive disorder may damage the immune system and result in immunosuppression. The CD4+/CD8 + T cell ratio is an indicator of immune regulation. In this study, we found that the CD4+/CD8 + T cell ratio of patients with severe depressive disorder was significantly lower, indicating a severe immune disorder.
Albumin, the most important protein in human plasma, is mainly produced by the liver, and it reflects the body,s nutrition balance and helps maintain its osmotic pressure. Hypoalbuminemia has been reported in patients with mood disorders in several previous studies [35–37]. In addition, a diet-controlled study also demonstrated that the serum albumin level was significantly lower in patients with depressive disorders than in normal volunteers and that the reduced albumin level was related to the severity of the disease when rated by HAMD score, which was consistent with the results of this study [38]. Psychiatric illness may influence the serum concentrations of albumin by altering daily behaviors such as ingestion, thus, hypoalbuminemia in patients with depressive disorders may be due to dietary deficiencies. Serum albumin is a routinely tested factor from peripheral blood and can be considered as an easily available biomarker for accurate classification of the severity of depressive disorder.
Monocytes originated from their progenitors in the bone marrow and are transported to the peripheral blood via the bloodstream. During the course of inflammation, circulating monocytes are recruited by series of chemokines and migrate into tissues, and then differentiated into macrophages or dendritic cells after conditioning by pro-inflammatory cytokines and microbial products. This process is essential for effective control of infection, and is involved in the pathogenesis of inflammatory and degenerative diseases [39]. A previous study found that the monocyte count and monocyte-to-lymphocyte ratio were significantly higher in patients with MDD than in healthy controls [40]. Similarly, another study found that patients with MDD exhibited significantly higher levels of serum pro-inflammatory IL-12 and IL-6, which were associated with increased numbers of circulating non-classical CD11b+CD16brightCD14neg monocytes and an increased activation state of classical CD40+CD86+ monocytes [41]. These findings were also consistent with the results of the present study, which showed that the peripheral blood M% was higher in patients with depressive disorder patients with severe disease, indicating the potential diagnostic value of monocyte counts.
Notably, a novel joint index based on the CD4+/CD8 + T cell ratio, albumin concentration and M% was developed in the present study,and it showed superior sensitivity and specificity to discriminate the severity of depressive disorder in comparison to the individual significant factors. Moreover, the jont index score also showed good discriminative performance in the validation cohort. This novel joint index was based on objective biological markers from peripheral blood, which could facilitate a more easily and accurate severity classification of depressive disorder.
Limitations
This study had a few limitations. First, healthy control populations were lacking. Second, the sample size was relatively small, and a prospective study with a larger study population, was required to verify the efficacy of the joint index. Finally, this study focused on treatment-naïve patients, and did not analyze the association between variations in laboratory parameters after subsequent therapy and changes in the depressive disorder status.