There are two independent serotonin systems in vertebrates that are regulated by the two different TPH enzymes with distinct functions as follows: tph1 usually plays important roles in peripheral effects such as hemostasis, immune, melatonin synthesis, migraine, and vasoconstriction; tph2 is often involved in effects of the CNS, such as aggression, anxiety, depression, epilepsy, food intake, and sleep. This evidence concerns the gene TPH1 and major depressive disorder.