Glial cell line-derived neurotrophic factor (GDNF) as a neurotrophic factor closely related to depression is able to promote the growth, proliferation, differentiation, and survival of multiple neurons. Clinical features, recurrence rates and suicide rates are significant different in major depressive disorder (MDD) according to age. GDNF level changes in the peripheral blood has been reported in patients with MDD. In this study, we aimed to investigate whether GDNF levels differentiated within various age groups and its relationship with age/clinical severity.MDD subjects and healthy controls (HC) are divided into younger (age 13-24 years) group (yMDD n = 35, yHC n = 44) and older (age 25-45 years) group (oMDD n = 30, oHC n = 55) based on the age of brain maturity. Clinical symptom severity was evaluated by the Hamilton Depression Rating Scale (HAMD-17) and the Hamilton Anxiety Rating Scale (HAMA-17). The levels of plasma GDNF were compared within subgroups.Plasma GDNF levels in yMDD patients were significantly decreased compared to yHC (yMDD 1.55 ± 0.46pg/ml, yHC 1.77 ± 0.47pg/ml, p < 0.05). Moreover, such difference was not found between oMDD group and oHC group. Our results also showed negative correlations between plasma GDNF levels and HAMD/HAMA scores (r = -0.33, p < 0.05; r = -0.39, p < 0.05).This study was underpowered to observe dynamic changes between age and GDNF in MDD due to the cross-sectional design of present study. We also failed to divided subjects into more age groups because of moderate sample size.The present result showed the level of protective neurotrophic factor GDNF associated with age in MDD, suggesting a relevance between GDNF and MDD subjects abnormal brain development in adolescent and young adult period.