However, other studies have proposed the hypothesis that the pro-inflammatory cytokines could increase the activity of tryptophan-2-3-dioxygenase, reducing serotoninergic neurotransmission in the brain and possibly leading to depressive symptoms, while efavirenz-treated mice expressed reduced TPO activity and higher serotonin against the occurrence of depression [28,29]. Here, TDO2 is linked to major depressive disorder.