TPH2 and major depressive disorder: Of note, tryptophan hydroxylase-2 (TpH2), a brain-specific isoform of the rate-limiting enzyme for 5-HT biosynthesis (Walther and Bader, 2003), has been implicated in the regulation of cognition, anxiety, and depression (Sun et al., 2004; Nash et al., 2005; You et al., 2005; Zhang et al., 2005).