The hypothalamic–pituitary–adrenal (HPA) axis is functionally involved in the pathophysiology of many neuropsychiatric disorders including major depressive disorder and cognitive dysfunction [130]; and tryptophan hydroxylase 2 (TPH2), rate-limiting enzyme of 5-HT synthesis in the brain, has been used as a therapeutic target for psychiatric disorders [131,132]. The gene discussed is TPH2; the disease is major depressive disorder.