BDNF and major depressive disorder: Subsequently, the increase of inflammatory cytokine levels causes BBB destruction [25, 62–74, 165], the dysfunction of neurotransmitters such as 5-HT [80–85], DA [86–97], NE [98–105], GABA [29, 30, 106–113] and Glu [79, 114–121], BDNF deficiency and dysfunction [26, 128–135], and attenuation of neuroplasticity [136–146], which are key factors in the onset and progression of depression (Fig. 10).