The current inability of clinical psychiatry to objectively select the most appropriate treatment is a major factor contributing to the severity and clinical burden of major depressive disorder (MDD). Here, we have attempted to identify plasma protein signatures in 39 MDD patients to predict response over a 6-week treatment period with antidepressants. LC-MS/MS analysis showed that differences in the levels of 29 proteins at baseline were found in the group with a favorable treatment outcome. Most of these proteins were components of metabolism or immune response pathways as well as multiple components of the coagulation cascade. After 6 weeks of treatment, 43 proteins were altered in responders of which 2 (alpha-actinin and nardilysin) had been identified at baseline. In addition, 46 proteins were altered in non-responders and 9 of these (alpha-actinin, alpha-2-macroglobulin, apolipoprotein B-100, attractin, C-reactive protein, fibrinogen alpha chain, fibrinogen beta chain, nardilysin and serine/threonine-protein kinase Chk1) had been identified at baseline. However, it should be stressed that the small sample size precludes generalization of the main results. Further studies to validate these as potential biomarkers of antidepressant treatment response are warranted considering the potential importance to the field of psychiatric disorders. This study provides the groundwork for development of novel objective clinical tests that can help psychiatrists in the clinical management of MDD through improved prediction and monitoring of patient responses to antidepressant treatments Ver menos