TrkB T1 over-expressing transgenic mice, which show reduced TrkB activation in the brain, are resistant to the effects of antidepressants (Saarelainen et al., 2003), whereas over-expression of TrkB led to resistance to depression-like behavior, with SSRI administration unable to further increase this resistance (Koponen et al., 2005) indicating that TrkB signaling is required for the behavioral benefits of antidepressants. The gene discussed is NTRK2; the disease is major depressive disorder.