['Availability of peripheral biomarkers for depression could aid diagnosis and help to predict treatment response. The objective of this work was to analyse the peripheral biomarker response in a gene-environment interaction model of depression. Genetically selected Flinders Sensitive Line (FSL) rats were subjected to maternal separation (MS), since early-life trauma is an important antecedent of depression. An open-ended approach based on a proteomic analysis of serum was combined with the evaluation of depression-associated proteins.', 'Rats experienced MS and chronically received escitalopram (ESC) or nortryptiline (NOR). Serum proteins were compared by two-dimensional gel electrophoresis. Corticosterone, cytokines, BDNF and C-reactive protein (CRP) were measured by immunoassays.', 'Comparing FSL with the control Flinders Resistant Line (FRL), Apo-AI and Apo-AIV, alpha1-macroglobulin, glutathione peroxidase and complement-C3 were significantly modulated. Significant increases were detected in leptin, interleukin (IL) 1alpha and BDNF. CRP levels were significantly reduced. The impact of early-life stress was assessed by comparing FSL+MS versus FSL. Apo-E, alpha1-macroglobulin, complement-C3, transferrin and hemopexin were significantly modulated. The effect of stress in antidepressant response was then evaluated. In the comparison FSL+ESC+MS versus FSL+ESC, albumin, alpha1-macroglobulin, glutathione peroxidase and complement-C3 were modulated and significant reductions were detected in IL4, IL6, IL10, CRP and BDNF. By comparing FSL+NOR+MS versus FSL+NOR proteins like Apo-AIV, pyruvate dehydrogenase, alpha1-macroglobulin, transferrin and complement-C3 showed different levels.'] Do early-life stress and antidepressants modulate peripheral biomarkers in a gene-environment rat model of depression?