TDO2 and adrenal gland hyperfunction: Hypercortisolism may contribute to serotonin (SER) depletion through activation of the initiating enzymes tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO), which divert tryptophan (Trp) metabolism toward the kynurenine pathway.