Fig. 4.

Putative schematic diagram of residual impairment in major depressive disorder remission. Inflammation can be activated in response to stressors. The four proteins discovered in this study––antithrombin-III (ANT3), serum amyloid A4 protein (SAA4), C1QB, and serum amyloid P-component––are related to inflammation, complement system, and anticoagulation, and these pathways interact with each other. Potentially, inflammation may contribute to the pathogenesis of depression, comprehensively affecting the peripheral-blood–brain barrier (BBB)-brain zone. The periphery and brain communicate bidirectionally. Inflammation that persists even in remission of major depressive disorder can impede recovery, resulting in residual symptoms (such as cognitive dysfunction) and, consequently, occupational, physical, and social impairments. Changes in inflammation, the complement system, and coagulation pathways may be associated with depression and bidirectional comorbidities.