Low levels of brain-derived neurotrophic factor (BDNF) are seen as an indicator of reduced neurotropic growth, a third important possible pathophysiological mechanism of MDD.14 A recent meta-analysis supports the idea that depressed patients have lower BDNF levels than controls.15 One study found that drug-free patients with a long index episode had significantly lower BDNF levels compared with patients with a shorter index episode.16 Here, BDNF is linked to major depressive disorder.