CRH and major depressive disorder: Since stress is one of the major causes of dysregulation of the hypothalamic–pituitary–adrenal axis and KCC2 has been shown to play a role in GABAergic regulation of corticotropin releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus, which is critical for triggering the body’s physiological stress response [45, 46], it seems that the role of KCC2 may be important in depression.