Protein biomarkers to distinguish between major depressive disorder and bipolar disorder

It is challenging to distinguish between major depressive disorder (MDD) and bipolar disorder (BD) owing to the clinical similarity of their depressive symptoms. The poor response of patients with BD to antidepressants emphasizes the need for disease-specific biomarkers. Therefore, we aimed to identify disease-specific biomarkers of MDD and BD. After obtaining sera from patients with MDD and BD, and healthy controls (HCs), a non-targeted qualitative analysis of the serum proteome was performed. Biomarkers whose expression was specifically altered in patients with MDD were selected and compared with those in HCs and patients with BD. Similarly, biomarkers that were specifically expressed in patients with BD were selected and compared with those in HCs and patients with MDD. The selected biomarker candidates were validated via multiple reaction monitoring (MRM). Vitamin D-binding proteins (DBP), complement factor H (CFH), and keratin, type I cytoskeletal 9 (K1C9) were identified as BD-specific biomarkers. They had the highest intensity levels in the BD group compared with those in the MDD and HC groups. Fibronectin, an MDD-specific biomarker, showed the lowest intensity in the MDD group. Our study provides molecular evidence to improve comprehension of the pathophysiological mechanisms of MDD and BD.