Developing an objectively diagnostic method with high specificity and sensitivity for MDD has been proven to be a formidable and elusive task, although we and other researchers have completed many meaningful works [14–17]. In the present work, a potential biomarker panel consisting of AAT, ALB and APOA was identified. We examined the diagnostic performance of this panel in two independent sets: in training set, the application of this panel resulted in an AUC of 0.974 (sensitivity, 91.7%; specificity, 92.8%); in testing set, the AUC was 0.878 (sensitivity, 92.3%; specificity, 80.0%). Moreover, the levels of these potential biomarkers had been improved after treatment. These results demonstrated that this biomarker panel might be a “good” classifier of MDD patients and HCs, and our findings could be helpful for future developing an objectively diagnostic method for MDD.
AAT has a variety of anti-inflammatory and tissue protection properties [18]. It could play an anti-inflammatory effect by regulating various immune cells, such as neutrophil and lymphocytes [19]. Thus, AAT has an important role in many chronic diseases, such as liver cirrhosis and gastric cancer [18]. In recent years, the role of inflammation and oxidative stress in the pathogenesis of neuropsychiatric diseases has been recognized by many scholars [20, 21]. Previous study showed that many MDD patients were accompanied by activation of the inflammatory response system (IRS), and then showed the compensatory immune regulatory response system (CIRS) activation [22]. As a positive acute phase response protein, AAT is an important component of CIRS. Therefore, there may be an important connection between AAT and MDD.
Some studies reported that the level of AAT was decreased in serum of MDD patients compared to non-depressed subjects [23, 24]. Another study found that the level of AAT was not significantly changed in plasma of depressed patients than in controls [25]. Using serum proteomics, we identified 74 differential proteins enriching in the acute phase response system, and AAT was found to be decreased in MDD patients than in HCs [11]. Meanwhile, Beiko et al. reported that anxiety and depression were common comorbidities in individuals with AAT deficiency [12]. In this study, we found that the AAT level in serum of MDD patients was the significantly decreased compared to HCs. This disparity may have resulted from differences in the demographic and clinical characteristics of the included MDD patients or HCs, sample sizes, and/or different races. However, the change of AAT level in MDD patients may be related to the phenomenon of oxidative stress during the onset of depression. MDD patients may consume large amounts of AAT for anti-inflammatory and immune regulation, then resulting in the decease of AAT level in serum.
There is a strong association between MDD and suicidal idea or behavior [26]. Here, we found that compared to MDD patients without suicidal idea or behavior, MDD patients with suicidal idea or behavior had the significantly lower average HDRS score. Our previous study found that suicidal behavior in MDD was associated with a more pronounced inflammatory phenotype [27]. In this study, we found that both suicidal idea and suicidal behavior were significantly negatively correlated with AAT, and suicidal behavior was also significantly negatively correlated with ALB and APOA. Moreover, the significantly lower average ALB and APOA levels were only found in MDD patients with suicidal behavior vs. MDD patients without suicidal behavior, not in MDD patients with suicidal idea vs. MDD patients without suicidal idea. These results might indicate that ALB and APOA were the two risk factors of MDD patients attempting suicide.
Several limitations of the present study should be taken into account when interpreting our findings. Firstly, the sample size was relatively small, future studies with large sample size are needed to validate and support our conclusions. Secondly, the present study was conducted with adult HCs and MDD patients; whether or not the results are appropriate for children, adolescents or an exclusive sample of elderly patients is unknown. Thirdly, the subjects were recruited in a city of China (Chongqing); whether similar results would have been obtained in MDD patients from other places, such as Africa, Europe and North America, cannot be determined from this study.