BDNF and major depressive disorder: The neurotrophin hypothesis is strongly supported by clinical evidence.20, 21, 22, 23, 24, 25, 26, 27 A large-scale meta-analysis of patients with MDD has shown low serum levels of BDNF.28 However, the hypothesis remains challenged by several issues.29 One issue is the causal relationship between lower serum levels of BDNF and the development of MDD:19, 28, 29 is serum BDNF a trait marker30, 31, 32, 33, 34 or a state marker33, 35, 36 of MDD?