For instance, brain-derived neurotrophic factor (BDNF) and mTOR signaling have been implicated in the antidepressant-like effects of ketamine in models of stress-induced depression (59, 60), but whether they also contribute to ketamine’s antidepressant-like effects in chronic pain–induced depression and how they interact with Tiam1-mediated signaling and synaptic plasticity remain to be determined. Here, TIAM1 is linked to major depressive disorder.